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1.
J Microbiol ; 59(2): 124-131, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33527314

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused corona virus disease 2019 (COVID-19) pandemic and led to mass casualty. Even though much effort has been put into development of vaccine and treatment methods to combat COVID-19, no safe and efficient cure has been discovered. Drug repurposing or drug repositioning which is a process of investigating pre-existing drug candidates for novel applications outside their original medical indication can speed up the drug development process. Raloxifene is a selective estrogen receptor modulator (SERM) that has been approved by FDA in 1997 for treatment and prevention of postmenopausal osteoporosis and cancer. Recently, raloxifene demonstrates efficacy in treating viral infections by Ebola, influenza A, and hepatitis C viruses and shows potential for drug repurposing for the treatment of SARS-CoV-2 infection. This review will provide an overview of raloxifene's mechanism of action as a SERM and present proposed mechanisms of action in treatment of viral infections.


Assuntos
Antivirais/uso terapêutico , Reposicionamento de Medicamentos , Cloridrato de Raloxifeno/uso terapêutico , /efeitos dos fármacos , Antagonistas de Estrogênios/uso terapêutico , Estrogênios/agonistas , Humanos , Simulação de Acoplamento Molecular , Osteoporose Pós-Menopausa/tratamento farmacológico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico
2.
Medicine (Baltimore) ; 99(40): e22542, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019463

RESUMO

BACKGROUND: The goal of this study was to review relevant randomized controlled trials or case-control studies to determine the clinical efficacy of minodronate in the treatment of osteoporosis. METHOD: The relevant studies were identified on PubMed, Cochrane, and Embase databases using appropriate keywords. Pertinent sources in the literature were also reviewed, and all articles published through October 2019 were considered for inclusion. For each study, we assessed odds ratios, mean difference, and 95% confidence interval (95% CI) to evaluate and synthesize outcomes. RESULT: Thirteen studies comprising 3740 patients were included in this study. Compared with other drugs, minodronate significantly decreased N-telopeptide of type I collagen/creatinine (weighted mean difference [WMD]: -13.669, 95% confidence interval [CI]: -23.108 to -4.229), bone alkaline phosphatase (BAP) (WMD: -1.26, 95% CI: -2.04 to -0.47) and tartrate-resistant acid phosphatase 5b (WMD: -154.11, 95% CI: -277.85 to -30.37). Minodronate combined with other drugs would significantly decrease BAP (WMD: -3.10, 95% CI: -5.20 to -1.00) than minodronate. Minodronate-naïve would significantly decrease BAP (WMD: -3.00, 95% CI: -5.47 to 0.53) and tartrate-resistant acid phosphatase 5b (WMD: -128.20, 95% CI: -198.11 to -58.29) than minodronate-switch. The incidence of vertebral fracture was significantly decreased in the minodronate group than the other drugs (relative risk: 0.520, 95% CI: 0.363-0.744). CONCLUSION: Minodronate has better clinical efficacy in the treatment of osteoporosis than other drugs (alendronate, risedronate, raloxifene, or eldecalcitol).


Assuntos
Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Osteoporose/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Alendronato/uso terapêutico , Fosfatase Alcalina/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Estudos de Casos e Controles , Colágeno Tipo I/efeitos dos fármacos , Creatinina , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cloridrato de Raloxifeno/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ácido Risedrônico/uso terapêutico , Fraturas da Coluna Vertebral/epidemiologia , Fosfatase Ácida Resistente a Tartarato/efeitos dos fármacos , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/uso terapêutico
5.
Am J Sports Med ; 48(9): 2161-2169, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32574070

RESUMO

BACKGROUND: Tearing and degeneration of the rotator cuff at the tendon-to-bone junction are common in adults aged ≥50 years. Few studies have reported on the relationship between estrogen and the rotator cuff enthesis. In addition to preventing bone loss, selective estrogen receptor modulators have been shown to improve tendon and muscle quality. PURPOSE: To evaluate the effects of raloxifene (RLX) and vitamin D on rotator cuff tendon-to-bone healing in a rat model. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 29 female rats (58 shoulders) were assigned to 4 groups: (1) control group, (2) ovariectomy (OVX)-only group, (3) no RLX group (OVX and rotator cuff repair [RCR]), and (4) RLX group (OVX, RCR, and RLX). Rats that did not undergo rotator cuff tear (RCT) surgery were divided into the control and OVX-only groups according to OVX surgery. Rats that underwent RCT surgery and RCR were divided into the no RLX and RLX groups according to RLX and vitamin D administration. An estrogen-deficient state was induced by OVX at 12 weeks of age. Bone mineral density (BMD) and trabecular bone characteristics were measured by micro-computed tomography, and healing of the tendon-to-bone junction was evaluated by biomechanical testing, histomorphometry, and micro-magnetic resonance imaging (MRI). RESULTS: The mean final body weight (BW; 461.6 ± 47.3 g) of the OVX-only group was significantly higher and BMD (0.25 ± 0.07 g/cm3) was significantly lower (P < .001) than the mean final BW (338.5 ± 35.1 g) and BMD (0.48 ± 0.05 g/cm3) of the control group. In contrast, the RLX group showed that the BW (369.6 ± 35.8 g) and BMD (0.41 ± 0.08 g/cm3) were not significantly different from the control group. The RLX group had a significantly higher histomorphometric total score (8.50 ± 1.05) than the no RLX group (4.83 ± 2.48). On biomechanical testing, the RLX group (29.7 ± 9.1 N) showed a significantly higher load to failure than the no RLX group (19.4 ± 8.8 N). On micro-MRI, the RLX group had a more homogeneous low signal and tendon continuity than the no RLX group. CONCLUSION: The combination treatment of RLX and vitamin D prevented a decrease in local BMD (greater tuberosity of the proximal humerus) and enhanced tendon-to-bone healing of the rotator cuff in a rat model. CLINICAL RELEVANCE: This study induced an estrogen-deficient state similar to the human postmenopausal state and used drugs that are actually being prescribed in a clinical situation.


Assuntos
Cloridrato de Raloxifeno/uso terapêutico , Lesões do Manguito Rotador , Manguito Rotador , Vitamina D/uso terapêutico , Animais , Fenômenos Biomecânicos , Feminino , Ovariectomia , Ratos , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/tratamento farmacológico , Lesões do Manguito Rotador/cirurgia , Cicatrização , Microtomografia por Raio-X
6.
J Bone Miner Res ; 35(6): 1009-1013, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32406536

RESUMO

Osteoporosis is a chronic condition that reflects reduced bone strength and an associated increased risk for fracture. As a chronic condition, osteoporosis generally requires sustained medical intervention(s) to limit the risks for additional bone loss, compromise of skeletal integrity, and fracture occurrence. Further complicating this issue is the fact that the abrupt cessation of some therapies can be associated with an increased risk for harm. It is in this context that the COVID-19 pandemic has brought unprecedented disruption to the provision of health care globally, including near universal requirements for social distancing. In this Perspective, we provide evidence, where available, regarding the general care of patients with osteoporosis in the COVID-19 era and provide clinical recommendations based primarily on expert opinion when data are absent. Particular emphasis is placed on the transition from parenteral osteoporosis therapies. It is hoped that these recommendations can be used to safely guide care for patients with osteoporosis until a return to routine clinical care standards is available. © 2020 American Society for Bone and Mineral Research.


Assuntos
Infecções por Coronavirus , Osteoporose/terapia , Pandemias , Pneumonia Viral , Absorciometria de Fóton , Biomarcadores/sangue , Densidade Óssea , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Continuidade da Assistência ao Paciente , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Denosumab/efeitos adversos , Denosumab/uso terapêutico , Gerenciamento Clínico , Esquema de Medicação , Terapia de Reposição de Estrogênios/efeitos adversos , Fraturas Espontâneas/prevenção & controle , Fraturas Espontâneas/terapia , Serviços de Assistência Domiciliar , Humanos , Imunossupressão/efeitos adversos , Osteoporose/sangue , Osteoporose/diagnóstico por imagem , Osteoporose/tratamento farmacológico , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Cloridrato de Raloxifeno/efeitos adversos , Cloridrato de Raloxifeno/uso terapêutico , Recidiva , Telemedicina , Trombofilia/induzido quimicamente , Trombofilia/etiologia , Procedimentos Desnecessários
8.
BMC Fam Pract ; 21(1): 32, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-32050909

RESUMO

BACKGROUND: Among Australians aged 50 and over, an estimated 1 in 4 men and 2 in 5 women will experience a minimal trauma fracture during their remaining lifetime. Effective fracture prevention is hindered by substantial undertreatment, even of patients who clearly warrant pharmacological therapy. Poor adherence to osteoporosis treatment is also a leading cause of repeat fractures and hospitalisation. The aim of this study was to identify current osteoporosis treatment patterns and gaps in practice in Australia, using general practice data, and to explore general practitioners' (GPs') attitudes to osteoporosis treatment and their views on patient factors affecting osteoporosis management. METHODS: The study was conducted in two phases. Phase 1 was a longitudinal retrospective cohort study which utilised data from MedicineInsight - a national general practice data program that extracts longitudinal, de-identified patient data from clinical information systems (CISs) of participating general practices. Phase 2 included semi-structured, in-depth telephone interviews with a sample of MedicineInsight practice GPs. Data were analysed using an inductive thematic analysis method informed by the theory of planned behaviour. RESULTS: A diagnosis of osteoporosis was recorded in 12.4% of patients over the age of 50 years seen in general practice. Of those diagnosed with osteoporosis, almost a quarter were not prescribed osteoporosis medicines. From 2012 to 17, there was a progressive increase in the number of denosumab prescriptions, while prescriptions for bisphosphonates and other osteoporosis medicines decreased. More than 80% of patients who ceased denosumab treatment had no subsequent bisphosphonate prescription recorded. Interviews with GPs revealed beliefs and attitudes that may have influenced their intentions towards prescribing and osteoporosis management. CONCLUSIONS: This study suggests that within the Australian general practice setting, osteoporosis is underdiagnosed and undertreated. In addition, it appears that most patients who ceased denosumab treatment had no record of subsequent antiresorptive therapy, which would place them at risk of further fractures. The study supports the need for the development of clinical education programs addressing GP knowledge gaps and attitudes, and the implementation of specific interventions such as good reminder/recall systems to avoid delays in reviewing and treating patients with osteoporosis.


Assuntos
Atitude do Pessoal de Saúde , Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Clínicos Gerais , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Padrões de Prática Médica/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Austrália , Desprescrições , Substituição de Medicamentos , Feminino , Medicina Geral , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Norpregnenos/uso terapêutico , Osteoporose/diagnóstico , Cloridrato de Raloxifeno/uso terapêutico , Estudos Retrospectivos , Teriparatida/uso terapêutico , Tiofenos/uso terapêutico
9.
J Womens Health (Larchmt) ; 29(1): 46-56, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31560601

RESUMO

Several organizations, including the American Society of Clinical Oncology, the National Comprehensive Cancer Network, and the United States Preventive Services Task Force, recommend incorporation of breast cancer risk-based counseling and chemoprevention into routine well-woman care. However, primary care providers report both discomfort with and a lack of medical knowledge on this topic. In this review we present a practical, evidence-based guide for incorporating breast cancer risk assessment and chemoprevention into routine care. We advocate a stepwise approach consisting of: (1) risk assessment and communication, (2) selection of appropriate chemoprevention based on risk-benefit analysis, (3) shared decision-making regarding chemoprevention, and (4) management of chemoprevention side effects. We encourage providers to identify high-risk women and refer them to genetic counseling or a high-risk breast cancer clinic. For women who are not considered high risk, we suggest using the Gail model to estimate a woman's 5-year risk of invasive breast cancer. Usually, the benefits of chemoprevention outweigh the risks of chemoprevention once a woman's 5-year risk of invasive breast cancer reaches 3%. For these women there are several factors that need to be considered when selecting a chemoprevention agent, including patient preference, thrombotic history, menopausal status, absence or presence of a uterus, and bone mineral density. We advocate an evidence-based shared decision-making approach that reflects the woman's individual preferences when communicating risk and counseling about chemoprevention. After starting a chemoprevention agent, close follow-up is important as side effects of chemoprevention are common, including vasomotor symptoms and arthralgias. We also review evidence-based management of chemoprevention side effects.


Assuntos
Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/prevenção & controle , Quimioprevenção , Atenção Primária à Saúde , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Anastrozol/uso terapêutico , Androstadienos/uso terapêutico , Tomada de Decisão Compartilhada , Feminino , Humanos , Pessoa de Meia-Idade , Relações Médico-Paciente , Cloridrato de Raloxifeno/uso terapêutico , Medição de Risco , Tamoxifeno/uso terapêutico
10.
Br J Gen Pract ; 69(689): e836-e842, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31636127

RESUMO

BACKGROUND: In Australia, evidence-based guidelines recommend that women consider taking selective oestrogen receptor modulators (SERMs) to reduce their risk of breast cancer. In practice, this requires effective methods for communicating the harms and benefits of taking SERMs so women can make an informed choice. AIM: To evaluate how different risk presentations influence women's decisions to consider taking SERMs. DESIGN AND SETTING: Cross-sectional, correlational study of Australian women in general practice. METHOD: Three risk communication formats were developed that included graphics, numbers, and text to explain the reduction in breast cancer risk and risk of side effects for women taking SERMs (raloxifene or tamoxifen). Women aged 40-74 years in two general practices were shown the risk formats using vignettes of hypothetical women at moderate or high risk of breast cancer and asked to choose 'If this was you, would you consider taking a SERM?' Descriptive statistics and predictors (risk format, level of risk, and type of SERM) of choosing SERMs were determined by logistic regression. RESULTS: A total of 288 women were recruited (an 88% response rate) between March and May 2017. The risk formats that showed a government statement and an icon array were associated with a greater likelihood of considering SERMs relative to one that showed a novel expected frequency tree. Risk formats for raloxifene and for the high-risk vignettes were also more strongly associated with choosing to consider SERMs. No associations were found with any patient demographics. CONCLUSION: Specific risk formats may lead to more women considering taking SERMs to reduce breast cancer risk, especially if they are at high risk of the condition. Raloxifene may be a more acceptable SERM to patients.


Assuntos
Neoplasias da Mama/prevenção & controle , Tomada de Decisões , Comunicação em Saúde/métodos , Atenção Primária à Saúde , Risco , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Austrália , Estudos Transversais , Feminino , Medicina Geral , Humanos , Modelos Logísticos , Educação de Pacientes como Assunto , Cloridrato de Raloxifeno/uso terapêutico , Medição de Risco , Tamoxifeno/uso terapêutico
11.
JAMA ; 322(9): 868-886, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479143

RESUMO

Importance: Medications to reduce risk of breast cancer are effective for women at increased risk but also cause adverse effects. Objective: To update the 2013 US Preventive Services Task Force systematic review on medications to reduce risk of primary (first diagnosis) invasive breast cancer in women. Data Sources: Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, EMBASE, and MEDLINE (January 1, 2013, to February 1, 2019); manual review of reference lists. Study Selection: Discriminatory accuracy studies of breast cancer risk assessment methods; randomized clinical trials of tamoxifen, raloxifene, and aromatase inhibitors for primary breast cancer prevention; studies of medication adverse effects. Data Extraction and Synthesis: Investigators abstracted data on methods, participant characteristics, eligibility criteria, outcome ascertainment, and follow-up. Results of individual trials were combined by using a profile likelihood random-effects model. Main Outcomes and Measures: Probability of breast cancer in individuals (area under the receiver operating characteristic curve [AUC]); incidence of breast cancer, fractures, thromboembolic events, coronary heart disease events, stroke, endometrial cancer, and cataracts; and mortality. Results: A total of 46 studies (82 articles [>5 million participants]) were included. Eighteen risk assessment methods in 25 studies reported low accuracy in predicting the probability of breast cancer in individuals (AUC, 0.55-0.65). In placebo-controlled trials, tamoxifen (risk ratio [RR], 0.69 [95% CI, 0.59-0.84]; 4 trials [n = 28 421]), raloxifene (RR, 0.44 [95% CI, 0.24-0.80]; 2 trials [n = 17 806]), and the aromatase inhibitors exemestane and anastrozole (RR, 0.45 [95% CI, 0.26-0.70]; 2 trials [n = 8424]) were associated with a lower incidence of invasive breast cancer. Risk for invasive breast cancer was higher for raloxifene than tamoxifen in 1 trial after long-term follow-up (RR, 1.24 [95% CI, 1.05-1.47]; n = 19 747). Raloxifene was associated with lower risk for vertebral fractures (RR, 0.61 [95% CI, 0.53-0.73]; 2 trials [n = 16 929]) and tamoxifen was associated with lower risk for nonvertebral fractures (RR, 0.66 [95% CI, 0.45-0.98]; 1 trial [n = 13 388]) compared with placebo. Tamoxifen and raloxifene were associated with increased thromboembolic events compared with placebo; tamoxifen was associated with more events than raloxifene. Tamoxifen was associated with higher risk of endometrial cancer and cataracts compared with placebo. Symptomatic effects (eg, vasomotor, musculoskeletal) varied by medication. Conclusions and Relevance: Tamoxifen, raloxifene, and aromatase inhibitors were associated with lower risk of primary invasive breast cancer in women but also were associated with adverse effects that differed between medications. Risk stratification methods to identify patients with increased breast cancer risk demonstrated low accuracy.


Assuntos
Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/prevenção & controle , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Tamoxifeno/uso terapêutico , Adulto , Área Sob a Curva , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/genética , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Mutação , Guias de Prática Clínica como Assunto , Cloridrato de Raloxifeno/efeitos adversos , Cloridrato de Raloxifeno/uso terapêutico , Medição de Risco/métodos , Fatores de Risco , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Tamoxifeno/efeitos adversos
12.
JAMA ; 322(9): 857-867, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479144

RESUMO

Importance: Breast cancer is the most common nonskin cancer among women in the United States and the second leading cause of cancer death. The median age at diagnosis is 62 years, and an estimated 1 in 8 women will develop breast cancer at some point in their lifetime. African American women are more likely to die of breast cancer compared with women of other races. Objective: To update the 2013 US Preventive Services Task Force (USPSTF) recommendation on medications for risk reduction of primary breast cancer. Evidence Review: The USPSTF reviewed evidence on the accuracy of risk assessment methods to identify women who could benefit from risk-reducing medications for breast cancer, as well as evidence on the effectiveness, adverse effects, and subgroup variations of these medications. The USPSTF reviewed evidence from randomized trials, observational studies, and diagnostic accuracy studies of risk stratification models in women without preexisting breast cancer or ductal carcinoma in situ. Findings: The USPSTF found convincing evidence that risk assessment tools can predict the number of cases of breast cancer expected to develop in a population. However, these risk assessment tools perform modestly at best in discriminating between individual women who will or will not develop breast cancer. The USPSTF found convincing evidence that risk-reducing medications (tamoxifen, raloxifene, or aromatase inhibitors) provide at least a moderate benefit in reducing risk for invasive estrogen receptor-positive breast cancer in postmenopausal women at increased risk for breast cancer. The USPSTF found that the benefits of taking tamoxifen, raloxifene, and aromatase inhibitors to reduce risk for breast cancer are no greater than small in women not at increased risk for the disease. The USPSTF found convincing evidence that tamoxifen and raloxifene and adequate evidence that aromatase inhibitors are associated with small to moderate harms. Overall, the USPSTF determined that the net benefit of taking medications to reduce risk of breast cancer is larger in women who have a greater risk for developing breast cancer. Conclusions and Recommendation: The USPSTF recommends that clinicians offer to prescribe risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women who are at increased risk for breast cancer and at low risk for adverse medication effects. (B recommendation) The USPSTF recommends against the routine use of risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, in women who are not at increased risk for breast cancer. (D recommendation) This recommendation applies to asymptomatic women 35 years and older, including women with previous benign breast lesions on biopsy (such as atypical ductal or lobular hyperplasia and lobular carcinoma in situ). This recommendation does not apply to women who have a current or previous diagnosis of breast cancer or ductal carcinoma in situ.


Assuntos
Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/prevenção & controle , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Tamoxifeno/uso terapêutico , Adulto , Neoplasias da Mama/genética , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Pessoa de Meia-Idade , Mutação , Cloridrato de Raloxifeno/uso terapêutico , Medição de Risco/métodos , Fatores de Risco
13.
Prev Med ; 129: 105834, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31494144

RESUMO

Several risk assessment models have been validated for the estimation of risk of breast cancer in women. Chemoprevention through hormonal therapy is an effective way to reduce the incidence of breast cancer in women with high risk. Selective estrogen receptor modulators, tamoxifen and raloxifene, are approved for this indication by the United States Food and Drug Administration, and aromatase inhibitors have also shown promise in recent studies. These medications are generally well tolerated, except for reported increased rates of fractures and venous thromboembolic events. Despite strong recommendations from several regulatory bodies, advocacy for chemoprevention has been inadequate in practice, more so among the primary care physicians. Studies have identified several barriers in physicians, patients, and the system, contributing to this problem. Lack of knowledge about risk assessment models and chemoprevention options preclude physicians from prescribing these medications with confidence. Fear of potential adverse events, confusion regarding the purpose of the therapy, and need for continued adherence for five years are among the principal reasons for reduced chemoprevention uptake and early discontinuation among patients. Multifaceted interventions directed at education and training of health care professionals, proper counseling of women at high risk, and promotion of the development of improved medications might help ensure better chemoprevention uptake in the target population.


Assuntos
Neoplasias da Mama/prevenção & controle , Quimioprevenção/métodos , Conhecimentos, Atitudes e Prática em Saúde , Médicos de Atenção Primária/psicologia , Feminino , Guias como Assunto , Humanos , Cloridrato de Raloxifeno/efeitos adversos , Cloridrato de Raloxifeno/uso terapêutico , Medição de Risco , Fatores de Risco , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Tamoxifeno/efeitos adversos , Tamoxifeno/uso terapêutico
14.
Cancer Prev Res (Phila) ; 12(11): 801-808, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31431499

RESUMO

Tamoxifen and raloxifene have been approved for the primary prevention of breast cancer in high-risk women, but are associated with an increased risk of serious side effects. Few studies have characterized risk-benefit profiles for chemoprevention among women who initiate tamoxifen or raloxifene outside of a clinical trial setting. Use of raloxifene and tamoxifen for chemoprevention was self-reported in 2014 to 2016 by participants in The Sister Study, a prospective cohort of women with a sister who had been diagnosed with breast cancer. After exclusions, 432 current raloxifene users and 96 current tamoxifen users were matched to 4,307 and 953 nonusers, respectively, on age and year of cohort enrollment. Conditional logistic regression was used to evaluate characteristics associated with chemoprevention use. Risk-benefit profiles were examined using published indices that assess the level of evidence (none, moderate, strong) that the benefits of chemoprevention outweigh the risk of serious side effects. Among current chemoprevention users, 44% of tamoxifen users and 5% of raloxifene users had no evidence of a net benefit. In analyses of factors associated with chemoprevention use, having strong evidence of benefit was a significant predictor of raloxifene use, but not of tamoxifen use. In our sample of women with a first-degree family history of breast cancer, raloxifene was more commonly used for breast cancer prevention than tamoxifen. Most raloxifene users, but <60% of tamoxifen users, were likely to benefit. Use of risk-benefit tables can help women and their healthcare providers make an informed decision about breast cancer chemoprevention.


Assuntos
Neoplasias da Mama/prevenção & controle , Antagonistas de Estrogênios/uso terapêutico , Predisposição Genética para Doença , Cloridrato de Raloxifeno/uso terapêutico , Medição de Risco/métodos , Tamoxifeno/uso terapêutico , Adulto , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
15.
s.l; RedARETS; ago. 2019. tab.
Não convencional em Espanhol | LILACS, BRISA/RedTESA | ID: biblio-1095359

RESUMO

CONTEXTO: La osteoporosis es un trastorno esquelético caracterizado por resistencia óssea comprometida, predisposición pacientes a un mayor riesgo de fractura. La prevalência aumenta del 6% de las mujeres de edad 50 a 59 años a más del 40% de las mujeres de edad 80 años y mayores.1 Consecuencias de mantener una fractura puede ser grave e incluir un aumento riesgo de fracturas posteriores, hospitalización o institucionalización, disminución de la calidad de vida, y mortalidad prematura, con una carga relacionada com el sistema de salud. DESCRIPCIÓN DE LA TECNOLOGÍA: El denosumab es un anticuerpo monoclonal que inhibe la resorción ósea producida por los osteoclastos. Fue comercializado en 2010 para el tratamiento de la osteoporosis. En estos años se han identificado varios efectos adversos potencialmente graves: predisposición a infecciones, cáncer, reacciones de hipersensibilidad, transtornos autoinmunes, e incremento de la incidencia de múltiples fracturas vertebrales espontáneas al suspender el tratamiento. En este número revisamos estas novedades. TECNOLOGÍAS ALTERNATIVAS: Los agentes antirresortivos como los bifosfonatos orales son el estándar tratamiento para la osteoporosis posmenopáusica, en conjunto con medidas no farmacológicas y sobre todo el énfasis en la prevención de las caídas. Otras opciones de tratamiento incluyen un bisfosfonatos intravenoso (ácido zoledrónico), un agente formador de hueso (teriparatida) y un modulador selectivo del receptor de estrógeno (raloxifeno). MÉTODOS: Se realizó una búsqueda bibliográfica utilizando las siguientes bases de datos bibliográficas: MEDLINE, EMBASE, The Cochrane Library, y PubMed. Aplicaron filtros metodológicos para evaluaciones de tecnología sanitaria, estudios económicos, revisiones sistemáticas, metanálisis, y ensayos controlados aleatorios (ECA). La búsqueda también se limitó a Idioma en Inglés y humanos. Se excluyeron los resúmenes de congresos en los resultados de búsqueda. Se identificó la literatura gris (literatura que no se publica comercialmente) fue identificado mediante la búsqueda de secciones relevantes de la Lista de verificación de Grey Matters (http://www.cadth.ca/en/resources/grey-matters). Google y otros motores de búsqueda de internet fueron se utiliza para buscar en la web adicional materiales Estas búsquedas se complementaron con revisar las bibliografías de documentos clave y a través de contactos con expertos apropiados. ESTRATEGIA DE BÚSQUEDA: Se realizó una búsqueda con última fecha 26/08/2019 en diversas bases de datos, incluidas PubMed y Embase, así como la biblioteca Cochrane, ClinicalTrials.gov y bases de datos de revisiones sistematicas Epistemonikos. La búsqueda sólo incluyó documentos escrito en ingles y espanol. RESULTADOS: Denosumab comparado con placebo para pacientes con osteoporosis. El riesgo en el grupo de intervención (y su intervalo de confianza del 95%) se basa en el riesgo asumido en el grupo de comparación y en el efecto relativo de la intervención (y su intervalo de confianza del 95%). Eficacia frente a bifosfonatos: comparaciones directas. Se evalúa el perfil de evidencia GRADE donde se evidencia el metaanálisis entre cuatro ECA 5-8 que comprendieron 2071 participantes con un rango de seguimiento de 12 a 24 meses y compararon el uso de Denosumab con bifosfonatos orales (Alendronato,Etidronato). Existe incertidumbre en el efecto de denosumab sobre el riesgo de fracturas en comparación con bifosfonatos. La certeza em la evidencia va desde BAJA A MUY BAJA considerando la presencia de imprecisión muy seria y el potencial riesgo de sesgo de publicación. Eficacia frente a bifosfonatos: comparaciones indirectas. No se han encontrado en la literatura comparaciones directas entre Denosumab y otros fármacos distintos. Esta recomendación de cobertura otorga más peso a la incertidumbre en la eficacia comparada con bifosfonatos, al potencial impacto presupuestario de su uso y la potencial reducción de la equidad; que a la preferencia de los pacientes respecto de la forma de administración de las drogas para osteoporosis.


Assuntos
Humanos , Feminino , Osteoporose Pós-Menopausa/tratamento farmacológico , Teriparatida/uso terapêutico , Cloridrato de Raloxifeno/uso terapêutico , Difosfonatos/uso terapêutico , Fraturas por Osteoporose/tratamento farmacológico , Denosumab/uso terapêutico , Ácido Zoledrônico/uso terapêutico , Avaliação da Tecnologia Biomédica , Análise Custo-Benefício/economia
16.
J Biochem Mol Toxicol ; 33(9): e22371, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31332895

RESUMO

Breast cancer is the most common cancer among women in the world and the incidence is increasing alarmingly. It was aimed to determine the effect of raloxifene (RAL) and fluoxetine (FLX) on selected parameters in 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma. Thirty-two female Wistar albino rats were assorted into four groups: DMBA (group I), DMBA+RAL (group II), DMBA+FLX (group III), and DMBA+RAL+FLX (group IV). Mammary tissue vascular endothelial growth factor (VEGF), macrophage colony-stimulating factor (M-CSF), matrix metalloproteinase-9 (MMP-9), and tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) levels were determined by the enzyme-linked immunosorbent assay method. The tissue VEGF levels were lower in group IV compared with DMBA group. Decreased M-CSF levels were observed in all therapeutic groups rather than the DMBA group, but the most effective decrease was found in group IV. Compared with the DMBA group, MMP-9 levels were statistically significantly decreased in group II and group IV. However, TIMP-1 levels were higher in the whole therapeutic groups rather than the DMBA group and the most effective increase was observed in group IV. Results of the present study suggest that combined therapy of RAL with FLX might lead to a better outcome targeting breast tumor.


Assuntos
9,10-Dimetil-1,2-benzantraceno/toxicidade , Antineoplásicos/uso terapêutico , Carcinógenos/toxicidade , Fluoxetina/uso terapêutico , Neoplasias Mamárias Experimentais/tratamento farmacológico , Cloridrato de Raloxifeno/uso terapêutico , Animais , Peso Corporal/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Feminino , Neoplasias Mamárias Experimentais/induzido quimicamente , Ratos , Ratos Wistar , Ganho de Peso/efeitos dos fármacos
17.
Bone ; 127: 199-206, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31233931

RESUMO

Current interventions to reduce skeletal fragility are insufficient at enhancing both the quantity and quality of bone when attempting to improve overall mechanical integrity. Bisphosphonates, such as Zoledronate (ZOL), are used to treat a variety of bone disorders by increasing bone mass to decrease fracture risk, but long-term use has been shown in some settings to compromise bone quality. Alternatively, Raloxifene (RAL) has recently been demonstrated to improve tissue quality and overall mechanical properties in a cell-independent manner by binding to collagen and increasing tissue hydration. We hypothesized that a combination of RAL and ZOL would improve mechanical and material properties of bone more than either monotherapy alone by enhancing both quantity and quality. In this study, wildtype (WT) and heterozygous (OIM+/-) male mice from the Osteogenesis Imperfecta (OI) murine model were treated with either RAL, ZOL, or both from 8 weeks to 16 weeks of age. Using the OIM model allows for investigation of therapeutic effects on a quality-based bone disease. Combination treatment resulted in higher trabecular architecture, cortical mechanical properties, and cortical fracture toughness in diseased mouse bone. Two fracture toughness properties, which are direct measures of the tissue's ability to resist the initiation and propagation of a crack, were significantly improved with combination treatment in OIM+/- compared to control. There was no significant effect on fracture toughness with either monotherapy alone in either genotype. Following the mass-based effects of ZOL, trabecular bone volume fraction was significantly higher with combination treatment in both genotypes. Combination treatment resulted in higher ultimate stress in both genotypes. RAL and combination treatment in OIM+/- also increased resilience compared to the control. In conclusion, this study demonstrates the beneficial effects of using combination drug treatments to increase bone mass while simultaneously improving tissue quality, especially to enhance the mechanical integrity of diseased bone. Combination therapies could be a potential method to improve bone health and combat skeletal fragility on both the microscopic and macroscopic levels.


Assuntos
Doenças Ósseas/tratamento farmacológico , Doenças Ósseas/fisiopatologia , Cloridrato de Raloxifeno/uso terapêutico , Ácido Zoledrônico/uso terapêutico , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Doenças Ósseas/patologia , Calcificação Fisiológica/efeitos dos fármacos , Osso Esponjoso/efeitos dos fármacos , Osso Esponjoso/patologia , Osso Esponjoso/fisiopatologia , Diáfises/efeitos dos fármacos , Diáfises/patologia , Diáfises/fisiopatologia , Quimioterapia Combinada , Fêmur/efeitos dos fármacos , Fêmur/patologia , Fêmur/fisiopatologia , Fraturas Ósseas/tratamento farmacológico , Fraturas Ósseas/patologia , Fraturas Ósseas/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Cloridrato de Raloxifeno/farmacologia , Ácido Zoledrônico/farmacologia
18.
J Clin Endocrinol Metab ; 104(5): 1595-1622, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30907953

RESUMO

OBJECTIVE: The objective is to formulate clinical practice guidelines for the pharmacological management of osteoporosis in postmenopausal women. CONCLUSIONS: Evidence from clinical trials and insights from clinical experience with pharmacologic therapies for osteoporosis were critically evaluated in formulating this guideline for the management of postmenopausal osteoporosis. Patient preferences, data on adherence and persistence, and risks and benefits from the patient and provider perspectives were also considered in writing committee deliberations. A consensus by the Writing Committee members was achieved for four management principles: (i) The risk of future fractures in postmenopausal women should be determined using country-specific assessment tools to guide decision-making. (ii) Patient preferences should be incorporated into treatment planning. (iii) Nutritional and lifestyle interventions and fall prevention should accompany all pharmacologic regimens to reduce fracture risk. (iv) Multiple pharmacologic therapies are capable of reducing fracture rates in postmenopausal women at risk with acceptable risk-benefit and safety profiles.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Absorciometria de Fóton , Acidentes por Quedas/prevenção & controle , Calcitonina/uso terapêutico , Cálcio/uso terapêutico , Tomada de Decisão Clínica , Moduladores de Receptor Estrogênico/uso terapêutico , Terapia de Reposição de Estrogênios , Feminino , Humanos , Norpregnenos/uso terapêutico , Osteoporose Pós-Menopausa/diagnóstico por imagem , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Preferência do Paciente , Cloridrato de Raloxifeno/uso terapêutico , Medição de Risco , Comportamento de Redução do Risco , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Teriparatida/uso terapêutico , Vitamina D/uso terapêutico
19.
Climacteric ; 22(2): 140-147, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30895900

RESUMO

Selective estrogen receptor modulators (SERMs) are synthetic non-steroidal agents which have variable estrogen agonist and antagonist activities in different target tissues. Tamoxifen is an anti-estrogen in the breast used for treatment and prevention of breast cancer, with estrogen agonist activity in the uterus. Raloxifene prevents and treats osteoporosis and prevents breast cancer, and can be safely combined with vaginal but not systemic estrogen. The tissue selective estrogen complex combines conjugated equine estrogens (CEE) with the SERM bazedoxifene (BZA). The five Selective Estrogen Menopause and Response to Therapy studies, with up to 2 years of data, demonstrated that CEE/BZA 0.45 mg/BZA 20 mg improved vasomotor symptoms and vulvovaginal atrophy, prevented bone loss, and was neutral on breast tenderness, breast density, with breast cancer incidence similar to placebo. Protection against estrogen-induced endometrial hyperplasia and cancer was found, with similar amenorrhea rates to placebo. Ospemifene is approved to treat dyspareunia, with potential benefits on bone and the breast, while lasofoxifene is being developed to treat resistant estrogen receptor-positive breast cancer in women. Estetrol is an estrogen synthesized exclusively during pregnancy by the human fetal liver and initially considered a weak estrogen, but it appears to have dual weak estrogenic/anti-estrogenic features.


Assuntos
Pós-Menopausa , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Adulto , Idoso , Atrofia/prevenção & controle , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/prevenção & controle , Estrogênios Conjugados (USP)/administração & dosagem , Estrogênios Conjugados (USP)/efeitos adversos , Feminino , Doenças Urogenitais Femininas/tratamento farmacológico , Fogachos/tratamento farmacológico , Humanos , Indóis/administração & dosagem , Indóis/efeitos adversos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/tratamento farmacológico , Cloridrato de Raloxifeno/uso terapêutico , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Tamoxifeno/uso terapêutico , Vagina/efeitos dos fármacos , Vagina/patologia
20.
J Midwifery Womens Health ; 64(3): 265-275, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30869832

RESUMO

Osteoporosis is described as a silent disease prior to fracture, and the sequelae of an osteoporotic fracture can be devastating. Primary care providers should routinely assess and remediate bone health during wellness visits for women aged at least 50 years. Assessment includes review of a variety of risk factors, bone density testing, and an online fracture risk assessment tool calculation. Diagnosis is based on bone density score and clinical risk factors. Evidence-based nonpharmacologic therapies are important adjuncts of care, and pharmacologic intervention may also be recommended. A variety of pharmacologic options are available for women with postmenopausal osteoporosis, and it is important to weigh benefits and risks. Pharmacologic indications, therapeutic variations among products, adverse effect profiles, administration considerations, and cost are addressed. Once pharmacotherapy is initiated, duration and drug holidays should also be considered. In general, medication benefits fade when treatment stops, so health care providers should be prepared to routinely revisit therapy indicators that will help define risk and guide treatment decisions. A comprehensive approach to bone health can make a valuable difference in the health of women.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osteoporose Pós-Menopausa/diagnóstico , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/prevenção & controle , Absorciometria de Fóton , Idoso , Calcitonina/uso terapêutico , Denosumab/uso terapêutico , Programas de Triagem Diagnóstica , Difosfonatos/uso terapêutico , Tratamento Farmacológico , Terapia de Reposição de Estrogênios , Medicina Baseada em Evidências , Feminino , Indicadores Básicos de Saúde , Humanos , Pessoa de Meia-Idade , Cloridrato de Raloxifeno/uso terapêutico , Medição de Risco , Fatores de Risco , Teriparatida/uso terapêutico , Vitaminas/uso terapêutico
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