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INTRODUCTION: Paget's disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment. METHODS: We randomised 222 individuals at increased risk of PDB because of pathogenic SQSTM1 variants to receive 5 mg zoledronic acid (ZA) or placebo. The primary outcome was new bone lesions assessed by radionuclide bone scan. Secondary outcomes included change in existing lesions, biochemical markers of bone turnover and skeletal events related to PDB. RESULTS: The median duration of follow-up was 84 months (range 0-127) and 180 participants (81%) completed the study. At baseline, 9 (8.1%) of the ZA group had PDB lesions vs 12 (10.8%) of the placebo group. Two of the placebo group developed new lesions versus none in the ZA group (OR 0.41, 95% CI 0.00 to 3.43, p=0.25). Eight of the placebo group had a poor outcome (lesions which were new, unchanged or progressing) compared with none of the ZA group (OR 0.08, 95% CI 0.00 to 0.42, p=0.003). At the study end, 1 participant in the ZA group had lesions compared with 11 in the placebo group. Biochemical markers of bone turnover were significantly reduced in the ZA group. One participant allocated to placebo required rescue therapy with ZA because of symptomatic disease. The number and severity of adverse events did not differ between groups. CONCLUSIONS: Genetic testing for pathogenic SQSTM1 variants coupled with intervention with ZA is well tolerated and has favourable effects on the progression of early PDB. TRIAL REGISTRATION NUMBER: ISRCTN11616770.
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Difosfonatos , Osteíte Deformante , Humanos , Difosfonatos/efeitos adversos , Osteíte Deformante/complicações , Osteíte Deformante/tratamento farmacológico , Osteíte Deformante/genética , Proteína Sequestossoma-1/genética , Ácido Zoledrônico/uso terapêutico , Testes Genéticos , BiomarcadoresRESUMO
INTRODUCTION: Individuals with concurrent tobacco dependence and other addictions often report symptoms of low mood and depression and as such may have more difficulty quitting smoking. We hypothesized that current symptoms of depression would be a significant predictor of quit success among a group of smokers receiving individualized treatment for tobacco dependence within addiction treatment settings. METHODS: Individuals in treatment for other addictions were enrolled in a smoking cessation program involving brief behavioral counseling and individualized dosing of nicotine replacement therapy. The baseline assessment included the Patient Health Questionnaire (PHQ9) for depression. Smoking cessation outcomes were measured at 3 and 6 months post-enrollment. Bivariate associations between cessation outcomes and PHQ9 score were analyzed. RESULTS: Of the 1,196 subjects enrolled to date, 1,171 (98%) completed the PHQ9. Moderate to severe depression (score >9) was reported by 28% of the sample, and another 29% reported mild depression (score between 5 and 9). Contrary to the extant literature and other findings by our own group, there was no association between current depression and cessation outcome at either 3 months (n = 1,171) (17.0% in those with PHQ9 > 9 vs. 19.8% in those with PHQ9 < 5, p = .32) or 6 months (n = 834) (17.8% vs. 18.9%, p = .74). CONCLUSIONS: Contrary to our hypothesis, depression severity as measured by the PHQ9 did not predict cessation outcome in this clinical population. A possible explanation may be the individualized treatment and supportive environment of an addictions treatment setting. These data indicate that patients in an addictions treatment setting can successfully quit smoking regardless of current depressive symptoms.
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Comportamento Aditivo/terapia , Depressão/terapia , Medicina de Precisão/métodos , Abandono do Hábito de Fumar/métodos , Fumar/terapia , Tabagismo/terapia , Adulto , Comportamento Aditivo/epidemiologia , Comportamento Aditivo/psicologia , Depressão/epidemiologia , Depressão/psicologia , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Medicina de Precisão/psicologia , Fumar/epidemiologia , Fumar/psicologia , Abandono do Hábito de Fumar/psicologia , Fatores de Tempo , Tabagismo/epidemiologia , Tabagismo/psicologia , Resultado do TratamentoRESUMO
BACKGROUND: Considerable public health efforts are ongoing Canada-wide to reduce the prevalence of smoking in the general population. From 1985 to 2005, smoking rates among adults decreased from 35% to 19%, however, since that time, the prevalence has plateaued at around 18-19%. To continue to reduce the number of smokers at the population level, one option has been to translate interventions that have demonstrated clinical efficacy into population level initiatives. Nicotine Replacement Therapy (NRT) has a considerable clinical research base demonstrating its efficacy and safety and thus public health initiatives in Canada and other countries are distributing NRT widely through the mail. However, one important question remains unanswered--do smoking cessation programs that involve mailed distribution of free NRT work? To answer this question, a randomized controlled trial is required. METHODS/DESIGN: A single blinded, panel survey design with random assignment to an experimental and a control condition will be used in this study. A two-stage recruitment process will be employed, in the context of a general population survey with two follow-ups (8 weeks and 6 months). Random digit dialing of Canadian home telephone numbers will identify households with adult smokers (aged 18+ years) who are willing to take part in a smoking study that involves three interviews, with saliva collection for 3-HC/cotinine ratio measurement at baseline and saliva cotinine verification at 8-week and 6-month follow-ups (N = 3,000). Eligible subjects interested in free NRT will be determined at baseline (N = 1,000) and subsequently randomized into experimental and control conditions to receive versus not receive nicotine patches. The primary hypothesis is that subjects who receive nicotine patches will display significantly higher quit rates (as assessed by 30 day point prevalence of abstinence from tobacco) at 6-month follow-up as compared to subjects who do not receive nicotine patches at baseline. DISCUSSION: The findings from the proposed trial are timely and highly relevant as mailed distribution of NRT require considerable resources and there are limited public health dollars available to combat this substantial health concern. In addition, findings from this randomized controlled trial will inform the development of models to engage smokers to quit, incorporating proactive recruitment and the offer of evidence based treatment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01429129.
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Serviços Postais , Abandono do Hábito de Fumar/métodos , Prevenção do Hábito de Fumar , Dispositivos para o Abandono do Uso de Tabaco , Adulto , Canadá , Cotinina/análise , Seguimentos , Humanos , Seleção de Pacientes , Projetos de Pesquisa , Saliva/química , Método Simples-Cego , Resultado do Tratamento , Adulto JovemRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0235709.].
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BACKGROUND: Since 2005, the Smoking Treatment for Ontario Patients (STOP) program has provided smoking cessation treatment of varying form and intensity to smokers through 11 distinct treatment models, either in-person at partnering healthcare organizations or remotely via web or telephone. We aimed to characterize the patient populations reached by different treatment models. METHODS: We linked self-report data to health administrative databases to describe sociodemographics, physical and mental health comorbidity, healthcare utilization and costs. Our sample consisted of 107,302 patients who enrolled between 18Oct2005 and 31Mar2016, across 11 models operational during different time periods. RESULTS: Patient populations varied on sociodemographics, comorbidity burden, and healthcare usage. Enrollees in the Web-based model were youngest (median age: 39; IQR: 29-49), and enrollees in primary care-based Family Health Teams were oldest (median: 51; IQR: 40-60). Chronic Obstructive Pulmonary Disease and hypertension were the most common physical health comorbidities, twice as prevalent in Family Health Teams (32.3% and 30.8%) than in the direct-to-smoker (Web and Telephone) and Pharmacy models (13.5%-16.7% and 14.7%-17.7%). Depression, the most prevalent mental health diagnosis, was twice as prevalent in the Addiction Agency (52.1%) versus the Telephone model (25.3%). Median healthcare costs in the two years up to enrollment ranged from $1,787 in the Telephone model to $9,393 in the Addiction Agency model. DISCUSSION: While practitioner-mediated models in specialized and primary care settings reached smokers with more complex healthcare needs, alternative settings appear better suited to reach younger smokers before such comorbidities develop. Although Web and Telephone models were expected to have fewer barriers to access, they reached a lower proportion of patients in rural areas and of lower socioeconomic status. Findings suggest that in addition to population-based strategies, embedding smoking cessation treatment into existing healthcare settings that reach patient populations with varying disparities may enhance equitable access to treatment.
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Aceitação pelo Paciente de Cuidados de Saúde , Fumantes/psicologia , Adulto , Comorbidade , Estudos Transversais , Depressão/epidemiologia , Depressão/patologia , Feminino , Custos de Cuidados de Saúde , Humanos , Hipertensão/epidemiologia , Hipertensão/patologia , Internet , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/patologia , Abandono do Hábito de Fumar , Inquéritos e Questionários , TelefoneRESUMO
Mutations in SQSTM1 are strongly associated with Paget's disease of bone (PDB), but little is known about the clinical characteristics of those with early disease. Radionuclide bone scans, biochemical markers of bone turnover, and clinical characteristics were analyzed in SQSTM1 mutation carriers who took part in the Zoledronic acid in the Prevention of Paget's disease (ZiPP) study. We studied 222 individuals, of whom 54.9% were female, with mean ± SE age of 50.1 ± 0.6 years. Twelve SQSTM1 mutations were observed, including p.Pro392Leu, which was present in 141 of 222 (63.5%) subjects. Bone scan examination revealed evidence of PDB in 20 subjects (9.0%), ten of whom (50%) had a single affected site. Participants with lesions were older than those without lesions but the difference was not significant (53.6 ± 9.1 versus 49.8 ± 8.9; p = .07). The mean age of participants with lesions was not significantly different from the age at which their parents were diagnosed with PDB (55 years versus 59 years, p = .17). All individuals with lesions were asymptomatic. Serum concentrations of total alkaline phosphatase (ALP) normalized to the upper limit of normal in each center were higher in those with lesions (0.75 ± 0.69 versus 0.42 ± 0.29 arbitary units; p < .0001). Similar findings were observed for other biochemical markers of bone turnover, but the sensitivity of ALP and other markers in detecting lesions was poor. Asymptomatic PDB is present in about 9% of SQSTM1 mutation carriers by the fifth decade. Further follow-up of this cohort will provide important information on the natural history of early PDB and its response to treatment. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
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Proteínas Adaptadoras de Transdução de Sinal , Osteíte Deformante , Proteína Sequestossoma-1 , Proteínas Adaptadoras de Transdução de Sinal/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Osteíte Deformante/epidemiologia , Osteíte Deformante/genética , Proteína Sequestossoma-1/genética , Ácido ZoledrônicoRESUMO
BACKGROUND: Clinical decision support systems (CDSSs) may promote practitioner adherence to evidence-based guidelines. This study examined if the addition of a CDSS influenced practitioner delivery of a brief intervention with treatment-seeking smokers who were drinking above recommended alcohol consumption guidelines, compared with practitioners who do not receive a CDSS prompt. METHODS: This was a cluster randomized controlled trial conducted in primary health care clinics across Ontario, Canada, implementing the Smoking Treatment for Ontario Patients (STOP) smoking cessation program. Clinics randomized to the intervention group received a prompt when a patient reported consuming alcohol above the Canadian Cancer Society (CCS) guidelines; the control group did not receive computer alerts. The primary outcome was an offer of an appropriate educational alcohol resource, an alcohol reduction workbook for patients drinking above the CCS guidelines, and an abstinence workbook to patients scoring above 20 points in the AUDIT screening tool; the secondary outcome was patient acceptance of the resource. The tertiary outcome was patient abstinence from smoking, and alcohol consumption within CCS guidelines, at 6-month follow-up. Results were analyzed using a generalized estimation approach for fitting logistic regression using a population-averaged method. RESULTS: Two hundred and twenty-one clinics across Ontario were randomized for this study; 110 to the intervention arm and 111 to the control arm. From the 15,222 patients that enrolled in the smoking cessation program, 15,150 (99.6% of patients) were screened for alcohol use and 5715 patients were identified as drinking above the CCS guidelines. No statistically significant difference between groups was seen in practitioner offer of an educational alcohol resource to appropriate patients (OR = 1.19, 95% CI 0.88-1.64, p = 0.261) or in patient abstinence from smoking and drinking within the CCS guidelines at 6-month follow-up (OR = 0.93, 95% CI 0.71-1.22, p = 0.594). However, a significantly greater proportion of patients in the intervention group accepted the alcohol resource offered to them by their practitioner (OR = 1.48, 95% CI 1.01-2.16, p = 0.045). CONCLUSION: A CDSS may not increase the likelihood of practitioners offering an educational alcohol resource, though it may have influenced patients' acceptance of the resource. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, number NCT03108144 , registered on April 11, 2017, "retrospectively registered".
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Consumo de Bebidas Alcoólicas/prevenção & controle , Sistemas de Apoio a Decisões Clínicas/organização & administração , Promoção da Saúde/organização & administração , Atenção Primária à Saúde/organização & administração , Abandono do Hábito de Fumar/métodos , Adulto , Sistemas de Apoio a Decisões Clínicas/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário , Psicoterapia Breve/organização & administraçãoRESUMO
INTRODUCTION: Paget's disease of bone (PDB) is characterised by increased and disorganised bone remodelling affecting one or more skeletal sites. Complications include bone pain, deformity, deafness and pathological fractures. Mutations in sequestosome-1 (SQSTM1) are strongly associated with the development of PDB. Bisphosphonate therapy can improve bone pain in PDB, but there is no evidence that treatment alters the natural history of PDB or prevents complications. The Zoledronate in the Prevention of Paget's disease trial (ZiPP) will determine if prophylactic therapy with the bisphosphonate zoledronic acid (ZA) can delay or prevent the development of PDB in people who carry SQSTM1 mutations. METHODS AND ANALYSIS: People with a family history of PDB aged >30 years who test positive for SQSTM1 mutations are eligible to take part. At the baseline visit, participants will be screened for the presence of bone lesions by radionuclide bone scan. Biochemical markers of bone turnover will be measured and questionnaires completed to assess pain, health-related quality of life (HRQoL), anxiety and depression. Participants will be randomised to receive a single intravenous infusion of 5 mg ZA or placebo and followed up annually for between 4 and 8 years at which point baseline assessments will be repeated. The primary endpoint will be new bone lesions assessed by radionuclide bone scan. Secondary endpoints will include changes in biochemical markers of bone turnover, pain, HRQoL, anxiety, depression and PDB-related skeletal events. ETHICS AND DISSEMINATION: The study was approved by the Fife and Forth Valley Research Ethics Committee on 22 December 2008 (08/S0501/84). Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results of this trial will inform clinical practice by determining if early intervention with ZA in presymptomatic individuals with SQSTM1 mutations can prevent or slow the development of bone lesions with an adverse event profile that is acceptable. TRIAL REGISTRATION NUMBER: ISRCTN11616770.
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Conservadores da Densidade Óssea/uso terapêutico , Osteíte Deformante/genética , Osteíte Deformante/prevenção & controle , Proteína Sequestossoma-1/genética , Ácido Zoledrônico/uso terapêutico , Adulto , Ansiedade/etiologia , Depressão/etiologia , Testes Genéticos , Humanos , Dor Musculoesquelética/etiologia , Mutação , Osteíte Deformante/complicações , Osteíte Deformante/diagnóstico por imagem , Qualidade de Vida , Cintilografia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Public health initiatives to distribute nicotine replacement therapy free of charge as a means of promoting smoking cessation are ongoing. Are there enough smokers interested in using nicotine replacement therapy to have a substantial impact on the prevalence of smoking if this aid were distributed free to all interested smokers? We conducted a telephone survey of 825 randomly selected daily smokers aged 18 years or older who had smoked at least 10 cigarettes per day at some point in their lives. Overall, 58.9% of the respondents said they would be interested in nicotine replacement therapy if it were offered for free. Of those interested, almost all (93.8%) said that they would use the nicotine replacement therapy to help them quit for good. There were differences in the levels of interest: smokers who intended to quit were more interested in using the nicotine replacement therapy than those who planned to reduce or maintain their smoking.
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Educação em Saúde/organização & administração , Agonistas Nicotínicos/administração & dosagem , Cooperação do Paciente/psicologia , Participação do Paciente/estatística & dados numéricos , Abandono do Hábito de Fumar/métodos , Adolescente , Adulto , Atitude Frente a Saúde , Estudos Transversais , Feminino , Programas Governamentais , Humanos , Intenção , Masculino , Pessoa de Meia-Idade , Ontário , Avaliação de Programas e Projetos de Saúde , Fumar/psicologia , Prevenção do Hábito de Fumar , Inquéritos e QuestionáriosRESUMO
PLAIN ENGLISH SUMMARY: The purpose of this paper is to describe a patient engagement event designed to create an educational workbook with smokers who drink alcohol at harmful levels. The goal was to create a workbook that combined scientific evidence with patients' values, preferences, and needs. Fourteen adult smokers who drink alcohol were invited to the Centre for Addiction and Mental Health (CAMH) to take part in a four-hour event to help design the workbook with the CAMH research team. Participants provided their opinions and ideas to create an outline for the workbook, including activities, images, and titles. The workbook - called Self-Awareness - is currently being offered in a smoking cessation program in 221 primary care clinics across Ontario to help smokers quit or reduce their harmful alcohol use. The patient engagement event was a useful way to co-create educational materials that incorporate both scientific research and patient needs. ABSTRACT: Background Evidence-based medicine is the integration of best research evidence with clinical expertise and patient values. There are few methodologies on how to design evidence-based programs and resources to include patient values. The latter is an important aspect of patient-centered care, and is essential for patients to trust the recommendations and empower them as consumers to make informed choices. This manuscript describes a participatory research approach to design patient-facing educational materials that incorporate both evidence-based and community-sensitive principles. These materials are intended to support smokers to reduce or stop harmful alcohol consumption. Methods Adult smokers who report consuming alcohol were invited to a co-creation meeting at the Centre for Addiction and Mental Health's Nicotine Dependence Service to guide the adaptation of evidence-based materials. The four-hour event consisted of individual reflections, group discussions, and consensus-building interactions. Detailed notes were taken and then incorporated into the material. Results Fourteen individuals participated in the event. The end product was a descriptive outline of an educational resource - entitled Self-Awareness - incorporating material from evidence-based workbooks and patient-driven features. Participants collaboratively selected the resource's content, structure, and titles. Conclusions This model describes a participatory research method that emphasizes the value of the patient perspective; preliminary evidence finds this adaptation approach can increase the adoption of resources. The process described in this article could be replicated in other settings to co-create evidence-based resources, interventions, and programs that reflect the needs of the community. Trial registration ClinicalTrials.gov NCT03108144. Retrospectively registered 11 April 2017.
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As a Supra-Regional Assay Service (SAS) laboratory, we receive samples from all over the UK. Of these some are sent frozen and others by post or courier. We have examined transport and storage conditions to see whether they affect the measurement of Vitamin D metabolites and potentially contribute to the variation in measurement of 25-hydroxyvitamin D (25OHD) seen in the DEQAS scheme. We have also examined the samples received during 2005. We found that different transport and storage conditions did not contribute significantly to the normal variation seen in measuring Vitamin D metabolites (CV% (+/-S.E.) for stored versus assay controls: 5.1+/-0.06% versus 4.5+/-0.04% for 25OHD and 10.8+/-1.0% versus 12.3+/-1.0% for 1,25D). A review of the service showed a 240% increase in samples received over the last 5 years. Despite an increased awareness of the need to measure Vitamin D status, in this cross-section of patient samples 92% of Asian and 86% of white patients were found to be Vitamin D-insufficient (<30 ng/ml) and 27% of Asian and 14% of white patients were profoundly deficient (<5 ng/ml) and at risk of bone disease.
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Vitamina D/análise , Vitamina D/metabolismo , Humanos , Reino UnidoRESUMO
We used a random-digit-dialed survey of 434 smokers to demonstrate that approximately three quarters of young adult (aged 19-24 years) smokers overestimated by 20% or more the proportion of their peers who smoked. The effect of this normative fallacy was significantly greater in young adult smokers than in smokers aged 25 years or older. Because of the strength of this false consensus effect in young adult smokers, normative feedback interventions might be especially effective in this age group.
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Conhecimentos, Atitudes e Prática em Saúde , Grupo Associado , Fumar/psicologia , Adulto , Fatores Etários , Idoso , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Fumar/epidemiologia , Prevenção do Hábito de FumarRESUMO
Using a representative sample of 434 daily smokers, this study tested the immediate impact of providing "safer smoking tips". As was predicted, a randomized half of respondents who were asked about their knowledge of "safer smoking tips" before being asked about their perceptions of choice about smoking rated their perceived choice as higher than respondents who were not asked the safer smoking tips first. However, the present study also provided evidence of the need for caution because hearing about safer smoking tips was associated with lower ratings of perceptions of health risks from smoking. Perceived choice has been identified as an important factor in change from negative health behaviors, and the implications and future directions of this research are discussed.
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Comportamento de Escolha , Redução do Dano , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Fumar/epidemiologia , Adulto , Feminino , Humanos , Masculino , Motivação , Autonomia Pessoal , Prevalência , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Tobacco and alcohol use present multiplicative risk for aerodigestive cancers. Reducing alcohol consumption improves smoking cessation outcomes and reduces cancer risk. Risky alcohol consumption and smoking are often treated separately despite concurrent treatment potentially leading to better outcomes for each. However, no rapidly scalable program exists for combined interventions in primary care clinics spread across wide geographic areas. This cluster randomized trial aims to report on the effects of a novel clinical decision support system (CDSS) on intervention rates by primary care practitioners addressing risky alcohol use in a smoking cessation program. METHODS/DESIGN: We will be implementing a clinical decision support system (CDSS) in 221 primary care sites participating in the Smoking Treatment for Ontario Patients (STOP) program across Ontario, Canada. Sites will be blindly allocated to one of two clinical decision support systems guiding practitioners to provide a risky alcohol use intervention to smokers attempting to quit using nicotine replacement therapy (NRT). Risky alcohol use is defined as drinking above the Canadian Cancer Society's low-risk drinking guidelines. Primary analysis will measure the proportion of risky drinkers offered an alcohol intervention in each CDSS arm at baseline. Patients will be contacted by phone or email to track smoking cessation and alcohol consumption rates at 6- and 12-month follow-up. DISCUSSION: Upon completion of the trial, the effect of different clinical decision support systems on practitioner behaviour, and on client tobacco and alcohol use, will be discussed. If the CDSS successfully promotes SBIRT for risky alcohol use in a primary care setting and/or improves patient-level outcomes, including smoking cessation rates and alcohol use reduction, this tool can be used as a model for other web-based behaviour change interventions integrated into primary care practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT03108144.
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Abstinência de Álcool , Promoção da Saúde/métodos , Neoplasias/prevenção & controle , Atenção Primária à Saúde/métodos , Comportamento de Redução do Risco , Dispositivos para o Abandono do Uso de Tabaco , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , OntárioRESUMO
It has been suggested that normalization of bone turnover may improve clinical outcome in Paget's disease of bone (PDB) by preventing complications such as fractures and the development of osteoarthritis. Here we investigated the long-term effects of a treatment strategy that aimed to normalize bone turnover in PDB with that of symptomatic treatment. The study group comprised 502 subjects who were enrolled into a 3-year extension of the Paget's Disease: Randomized Trial of Intensive versus Symptomatic Management (PRISM) study. Intensive bisphosphonate therapy was continued in 270 of these subjects with the aim of normalizing bone turnover using zoledronic acid as the treatment of first choice. Symptomatic treatment continued in 232 subjects in whom bisphosphonates were only given for the treatment of bone pain. The primary outcome was fracture and secondary outcomes were orthopedic procedures, quality of life, and bone pain, adjusted for baseline characteristics. Serum total alkaline phosphatase (ALP) concentrations were significantly lower in the intensive group on entry to the study and the differences between groups increased as the study progressed. There were no clinically important differences in quality of life measures or bone pain between the treatment groups. Intensive treatment was associated with a nonsignificant increase in fracture risk (hazard ratio = 1.90; 95% CI, 0.91 to 3.98; p = 0.087), orthopedic procedures (1.81; 95% CI, 0.71 to 4.61; p = 0.214), and serious adverse events (relative risk 1.28; 95% CI, 0.96 to 1.42). We conclude that long-term intensive bisphosphonate therapy confers no clinical benefit over symptomatic therapy and is associated with a nonsignificant increase in the risk of fractures, orthopedic events, and serious adverse events. The results of this study suggest that in patients with established PDB, bisphosphonate therapy should focus on control of symptoms rather than suppression of bone turnover. © 2016 American Society for Bone and Mineral Research.
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Osteíte Deformante/terapia , Idoso , Fosfatase Alcalina/sangue , Analgésicos/uso terapêutico , Difosfonatos/uso terapêutico , Feminino , Fraturas Ósseas/complicações , Humanos , Masculino , Procedimentos Ortopédicos , Osteíte Deformante/sangue , Osteíte Deformante/tratamento farmacológico , Dor/tratamento farmacológico , Qualidade de VidaRESUMO
UNLABELLED: Previous studies have implicated CDV in the pathogenesis of Paget's disease; however, there has been no direct evidence that CDV can infect human cells. We studied the effects of CDV on osteoclastogenesis in vitro and showed that CDV had a dose-dependent effect on osteoclastogenesis, through a possible mechanism involving activation of NF-kappaB and sequestosome 1/p62. INTRODUCTION: Paget's disease is characterized by a dramatic increase in size and number of osteoclasts. The etiology of the disorder is still unclear; however, evidence points to either a viral infection or a genetic susceptibility or a combination of both. Previously, we have shown that canine distemper virus (CDV) RNA is present in Pagetic bone. However, the effects of CDV on human osteoclast formation in vitro have not been studied previously. MATERIALS AND METHODS: Replicate cultures (n = 5) of purified human osteoclast precursors were infected with increasing doses of CDV and cultured on dentine slices for 14 days. Osteoclasts were stained for TRACP, and the dentine slices were examined for evidence of resorption. Control cells were incubated in the absence of virus. In each case, 10 high-power microscopy fields were analyzed. Immunocytochemical analyses were performed for p65, Gab2, sequestosome 1/p62, and ubiquitin. RESULTS: CDV dose-dependently increased osteoclast number and size (p < 0.0001, ANOVA), and there was a concomitant increase in resorption (p < 0.0001, ANOVA). CDV infection induced nuclear translocation of p65 and led to a dramatic increase in sequestosome 1/p62 and ubiquitin expression. CONCLUSIONS: These results provide the first conclusive proof that CDV can infect and replicate in human osteoclast precursors, raising possible zoonotic implications for CDV. The increased osteoclastogenesis is accompanied by NF-kappaB and sequestosome 1/p62 activation. This study provides further evidence for the possible role of paramyxoviruses in the pathogenesis of Paget's disease.
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Vírus da Cinomose Canina/metabolismo , NF-kappa B/metabolismo , Osteíte Deformante/patologia , Osteoclastos/metabolismo , Osteoclastos/virologia , Proteínas Adaptadoras de Transdução de Sinal , Humanos , Imuno-Histoquímica , Osteíte Deformante/virologia , Paramyxoviridae/metabolismo , Proteínas/metabolismo , Proteína Sequestossoma-1RESUMO
INTRODUCTION: Providing free nicotine replacement therapy (NRT) can be a cost-effective strategy for increasing quit attempts and cessation rates at a population level. However, the optimal amount of NRT to provide is unknown. Associations between duration of NRT use and abstinence may be overestimated as a result of reverse causality due to discontinuation following relapse. We examined the association between adherence to 10weeks of cost-free NRT and quit success at 6-month follow-up, after controlling for reverse causation by excluding participants who reported nonadherence due to relapse. METHODS: Individuals 18years or older who smoked at least 10 cigarettes daily and intended to quit within 30days received 10weeks of NRT at a smoking cessation workshop. There were 3922 participants who attended one of 114 workshops in 70 different localities in Ontario, Canada from 2007 to 2008. RESULTS: At end of treatment participants were asked whether they had used "all" of the NRT (20%), "most" of it (28%), "some" of it (47%), or whether they "did not use any" of it (5%). After controlling for reverse causation and adjusting for potential confounding variables, poorer quit success was reported by those who used either some (AOR=0.43, 95% CI=0.26-0.69, p=0.001) or none (AOR=0.30, 95% CI=0.09-0.95, p=0.041) of the NRT versus all 10weeks. Post-estimation contrasts revealed using some versus most of the NRT was also associated with poorer quit success (p=0.026). CONCLUSIONS: After controlling for reverse causation, adherence to 10weeks of cost-free NRT was associated with successful abstinence at six months post-treatment.
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Cooperação do Paciente/estatística & dados numéricos , Abandono do Hábito de Fumar/economia , Abandono do Hábito de Fumar/métodos , Dispositivos para o Abandono do Uso de Tabaco/economia , Dispositivos para o Abandono do Uso de Tabaco/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário , Resultado do TratamentoRESUMO
Previous evidence implicating Paramyxoviruses in the aetiopathology of Paget's disease of bone has proved controversial. Whilst several groups have demonstrated Paramyxoviruses using techniques such as in situ hybridisation (ISH), reverse transcriptase-polymerase chain reaction (RT-PCR), and in situ-RT-PCR (IS-RT-PCR), others have found no evidence of viruses using only RT-PCR. To investigate this latter finding, we have now compared detection of canine distemper virus by ISH, RT-PCR (three different methods) and IS-RT-PCR, in 10 patients with Paget's disease, and samples of non-diseased bone from four patients. Canine distemper virus was detectable in six of the samples by ISH, but only in five of the samples by RT-PCR, using one of the methods. Neither of the other RT-PCR methods detected canine distemper virus. IS-RT-PCR demonstrated canine distemper virus in all 10 samples. There was no evidence of virus in the control samples. We have shown that the ability to detect canine distemper virus in bone is dependent on the technique used. IS-RT-PCR clearly showed that canine distemper virus was present in 100% of Pagetic samples, whereas canine distemper virus was only found in 60% by ISH and in 50% using one particular RT-PCR method. These results provide conclusive evidence that canine distemper virus is present within Pagetic bone, and provide a possible explanation for the failure of some groups to detect Paramyxovirus sequences. These findings also have wider implications for other studies investigating viral expression.
Assuntos
Vírus da Cinomose Canina/isolamento & purificação , Hibridização In Situ/métodos , Osteíte Deformante/virologia , RNA Viral/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Vírus da Cinomose Canina/genética , HumanosRESUMO
BACKGROUND: Low bone mineral density (BMD) is prevalent in adults with cystic fibrosis and might be related to calcium and vitamin D malabsorption from the gastrointestinal tract. The aim of this study was to investigate the effect of calcium and vitamin D supplementation on BMD and bone metabolism in these subjects. METHODS: Patients were invited to participate if they had a BMD Z score of -1 or less in the lumbar spine, proximal femur or distal forearm. Patients were randomised to receive calcium 1 g+vitamin D 800 IU or placebo daily, in addition to their regular vitamin D supplements (900 IU/day). BMD and bone biochemical markers were measured before and after 1 year of treatment. RESULTS: After 12 months, the treatment group (n=15) showed a reduced rate of bone loss compared with the control group (n=15) in the lumbar spine (mean difference 1.9% [CI -0.9% to 4.6%]), total hip (mean difference 0.7% [CI -2.2% to 3.5%]) and distal forearm (mean difference 1.7% [CI -2.2% to 5.5%]), but these changes did not reach statistical significance. There was also a trend towards a reduction in bone turnover in the treatment group. CONCLUSIONS: Calcium and vitamin D supplementation reduced the rate of bone turnover and bone loss in adult patients with cystic fibrosis, but these changes did not reach statistical significance. These data suggest that a longer term trial of this simple intervention would be justified.
Assuntos
Densidade Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Cálcio/administração & dosagem , Fibrose Cística/tratamento farmacológico , Suplementos Nutricionais , Vitamina D/administração & dosagem , Absorciometria de Fóton , Administração Oral , Adolescente , Adulto , Fibrose Cística/metabolismo , Método Duplo-Cego , Fêmur/metabolismo , Seguimentos , Humanos , Vértebras Lombares/metabolismo , Estudos RetrospectivosRESUMO
Expenditure on treating osteoporotic fractures and on preventative intervention is considerable and is likely to rise in forthcoming years due to the association between fracture risk and age. With funders such as the National Institute for Health and Care Excellence and the Pharmaceutical Benefits Advisory Committee explicitly considering cost-effectiveness analyses within the process of producing guidance, it is imperative that economic models are as robust as possible. This article details issues that need to be considered specifically related to health technology assessments of interventions for osteoporosis, and highlights limitations within the current evidence base. A likely direction of impact on cost effectiveness of addressing the key issues has been included alongside a tentative categorization of the level of these impacts. It is likely that cost-effectiveness ratios presented in previous models that did not address the identified issues were favourable to interventions.