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1.
Eur Respir J ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980498

RESUMO

BACKGROUND: Clinical trials suggest less hepatotoxicity and better adherence with 4 months rifampin (4R) versus 9 months isoniazid (9H) for treating latent tuberculosis infection (LTBI). Our objectives were to compare frequencies of severe hepatic adverse events and treatment completion, and direct health system costs of LTBI regimens 4R and 9H, in the general population of the province of Quebec, Canada, using provincial health administrative data. METHODS: Our retrospective cohort included all patients starting rifampin or isoniazid regimens between 2003 and 2007. We estimated hepatotoxicity from hospitalisation records, treatment completion from community pharmacy records, and direct costs from billing records and fee schedules. We compared rifampin to isoniazid using logistic (hepatotoxicity), log-binomial (completion), and gamma (costs) regression, with adjustment for age, co-morbidities, and other confounders. RESULTS: 10 559 individuals started LTBI treatment (9684 isoniazid; 875 rifampin). Rifampin patients were older with more baseline co-morbidities. Severe hepatotoxicity risk was higher with isoniazid (n=15) than rifampin (n=1), adjusted OR=2.3 (95%CI: 0.3,16.1); there were 2 liver transplants and 1 death with isoniazid and none with rifampin. Overall, patients without co-morbidities had lower hepatotoxicity risk (0.1% versus 1.0%). 4R completion (53.5%) was higher than 9H (36.9%), adjusted RR=1.5 (95%CI:1.3,1.7). Mean costs per patient were lower for rifampin than isoniazid: adjusted Cost Ratio=0.7 (95%CI:0.5,0.9). CONCLUSION: Risk of severe hepatotoxicity and direct costs were lower, and completion was higher, for 4R than 9H, after adjustment for age and co-morbidities. Severe hepatotoxicity resulted in death or liver transplant in three patients receiving 9H, compared to no patients receiving 4R.

2.
J Gastrointest Surg ; 24(1): 115-122, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31367895

RESUMO

INTRODUCTION: Treatment delay may have detrimental effects on cancer outcomes. The impact of longer delays on colorectal cancer outcomes remains poorly described. The objective of this study was to determine the effect of delays to curative-intent surgical resection on survival in colorectal cancer patients. METHODS: All adult patients undergoing elective resection of primary non-metastatic colorectal adenocarcinoma from January 2009 to December 2014 were reviewed. Treatment delays were defined as the time from tissue diagnosis to definitive surgery, categorized as < 4, 4 to < 8, and ≥ 8 weeks. Primary outcomes were 5-year disease-free (DFS) and overall survival (OS). Statistical analysis included Kaplan-Meier curves and Cox regression models. RESULTS: A total of 408 patients were included (83.2% colon;15.8% rectal) with a mean follow-up of 58.4 months (SD29.9). Fourteen percent (14.0%) of patients underwent resection < 4 weeks, 40.0% 4 to < 8 weeks, and 46.1% ≥ 8 weeks. More rectal cancer patients had treatment delay ≥ 8 weeks compared with colonic tumors (69.8% vs. 41.4%, p < 0.001). Cumulative 5-year DFS and OS were similar between groups (p = 0.558; p = 0.572). After adjusting for confounders, surgical delays were not independently associated with DFS and OS. CONCLUSIONS: Treatment delays > 4 weeks were not associated with worse oncologic outcomes. Delaying surgery to optimize patients can safely be considered without compromising survival.

3.
J Clin Tuberc Other Mycobact Dis ; 16: 100108, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31720432

RESUMO

To attain the Global End Tuberculosis (TB) goals, the treatment of persons with TB requires advancements in coordinated approaches that are low-cost and highly accessible. Treating TB successfully requires prolonged medication regimens with good adherence, which in turn requires patients to be adequately supported. Furthermore, TB care-providers often wish to monitor treatment-taking by patients in order to track the success of their programs and ensure adequate completion of therapies by individuals. The standard-of-care for treatment monitoring in TB programs often includes directly observed therapy (DOT). Video observed therapy (VOT) has emerged as a method to mimic in-person visits or observations, especially in the smartphone era with internet data connections, but remains simply inaccessible to patients in areas where TB is most endemic. Both approaches may be considered more intensive than necessary for many patients, leaving an opportunity for more affordable and acceptable approaches. The rapid increase in mobile phone penetration provides an opportunity to reach patients between clinical visits. Short message services (SMS) are available on almost every mobile phone and are supported by first generation cellular communication networks, thus providing the farthest reach and penetration globally. Evidence from non-TB conditions suggests SMS, used in a variety of ways, may support outpatients for better medication adherence and quality of care but the evidence in TB remains limited. In this paper, we discuss how basic mobile phones and SMS-related services may be used in supporting global care of persons with TB, with a focus on patient-centered approaches.

4.
Ann Surg ; 270(3): 493-501, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31318793

RESUMO

OBJECTIVE: The objective of this study was to investigate the effect of prehabilitation on survival after colorectal cancer surgery. SUMMARY OF BACKGROUND DATA: Preoperative multimodal exercise and nutritional programs (prehabilitation) improve functional capacity and recovery following colorectal surgery. Exercise may also affect cancer outcomes by mediating the systemic inflammatory response. The effect of prehabilitation on cancer outcomes is unknown. METHODS: Pooled data from 3 prehabilitation trials (2 randomized controlled trials, 1 cohort) in patients undergoing elective, biopsy-proven, primary non-metastatic colorectal cancer surgery from 2009 to 2014 within an enhanced recovery program were analyzed. Patients were grouped into +prehab or-prehab. The primary outcomes were 5-year disease-free (DFS) and overall survival (OS). DFS and OS were analyzed using Kaplan-Meier curves and multiple Cox regression. RESULTS: A total of 202 patients were included (+prehab 104, -prehab 98). Median prehabilitation duration was 29 days (interquartile range 20-40). Patient and tumor characteristics were well-balanced (33% stage III). Postoperative complications and time to adjuvant chemotherapy were similar. Mean duration of follow-up was 60.3 months (standard deviation 26.2). DFS was similar for the combined group of stage I-III patients (P = 0.244). For stage III patients, prehabilitation was associated with improved DFS (73.4% vs 50.9%, P = 0.044). There were no differences in OS (P = 0.226). Prehabilitation independently predicted improved DFS (hazard ratio 0.45; 95% confidence interval, 0.21-0.93), adjusting for stage and other confounders. Prehabilitation did not independently predict OS. CONCLUSION: In this report, prehabilitation is associated with improved 5-year DFS in stage III colorectal cancer. This finding should be confirmed in future trials.

5.
PLoS Med ; 16(6): e1002824, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31170161

RESUMO

In a Perspective for the Tuberculosis Special Issue, Kevin Schwartzman and colleagues discuss the choices and implications for personal versus public health benefits when pursuing tuberculosis elimination in low-incidence countries.


Assuntos
Antituberculosos/uso terapêutico , Política de Saúde/tendências , Tuberculose Latente/epidemiologia , Tuberculose Latente/prevenção & controle , Humanos , Incidência , Tuberculose Latente/diagnóstico , Medição de Risco/métodos , Medição de Risco/tendências , Resultado do Tratamento
6.
Clin Infect Dis ; 69(12): 2101-2108, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-30856258

RESUMO

BACKGROUND: Latent tuberculosis infection (LTBI) screening and treatment is a key component of the World Health Organization (WHO) EndTB Strategy, but the impact of LTBI screening and treatment at a population level is unclear. We aimed to estimate the impact of LTBI screening and treatment in a population of migrants to British Columbia (BC), Canada. METHODS: This retrospective cohort included all individuals (N = 1 080 908) who immigrated to Canada as permanent residents between 1985 and 2012 and were residents in BC at any time up to 2013. Multiple administrative databases were linked to identify people with risk factors who met the WHO strong recommendations for screening: people with tuberculosis (TB) contact, with human immunodeficiency virus, on dialysis, with tumor necrosis factor-alpha inhibitors, who had an organ/haematological transplant, or with silicosis. Additional TB risk factors included immunosuppressive medications, cancer, diabetes, and migration from a country with a high TB burden. We defined active TB as preventable if diagnosed ≥6 months after a risk factor diagnosis. We estimated the number of preventable TB cases, given optimal LTBI screening and treatment, based on these risk factors. RESULTS: There were 16 085 people (1.5%) identified with WHO strong risk factors. Of the 2814 people with active TB, 118 (4.2%) were considered preventable through screening with WHO risk factors. Less than half (49.4%) were considered preventable with expanded screening to include people migrating from countries with high TB burdens, people who had been prescribed immunosuppressive medications, or people with diabetes or cancer. CONCLUSIONS: The application of WHO LTBI strong recommendations for screening would have minimally impacted the TB incidence in this population. Further high-risk groups must be identified to develop an effective LTBI screening and treatment strategy for low-incidence regions.

7.
BMC Med ; 17(1): 26, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30712513

RESUMO

BACKGROUND: Tuberculosis (TB) remains a significant public health problem in Canadian Inuit communities. In 2016, Canadian Inuit had an incidence rate 35 times the Canadian average. Tobacco use is an important risk factor for TB, and over 60% of Inuit adults smoke. We aimed to estimate changes in TB-related outcomes and costs from reducing tobacco use in Inuit communities. METHODS: Using a transmission model to estimate the initial prevalence of latent TB infection (LTBI), followed by decision analysis modelling, we conducted a cost-effectiveness analysis that compared the current standard of care for management of TB and LTBI without additional tobacco reduction intervention (Status Quo) with (1) increased tobacco taxation, (2) pharmacotherapy and counselling for smoking cessation, (3) pharmacotherapy, counselling plus mass media campaign, and (4) the combination of all these. Projected outcomes included the following: TB cases, TB-related deaths, quality-adjusted life years (QALYs), and health system costs, all over 20 years. RESULTS: The combined strategy was projected to reduce active TB cases by 6.1% (95% uncertainty range 4.9-7.0%) and TB deaths by 10.4% (9.5-11.4%) over 20 years, relative to the status quo. Increased taxation was the only cost-saving strategy. CONCLUSIONS: Currently available strategies to reduce commercial tobacco use will likely have a modest impact on TB-related outcomes in the medium term, but some may be cost saving.


Assuntos
Fumar Tabaco/efeitos adversos , Fumar Tabaco/prevenção & controle , Abandono do Uso de Tabaco/economia , Abandono do Uso de Tabaco/métodos , Tuberculose/prevenção & controle , Adulto , Canadá/epidemiologia , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Humanos , Inuítes , Tuberculose Latente/epidemiologia , Tuberculose Latente/prevenção & controle , Prevalência , Saúde Pública/métodos , Fatores de Risco , Tuberculose/epidemiologia , Tuberculose/etiologia
8.
Lancet Glob Health ; 7(1): e68-e80, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30554764

RESUMO

BACKGROUND: Indigenous peoples worldwide carry a disproportionate tuberculosis burden. There is an increasing awareness of the effect of social determinants and proximate determinants such as alcohol use, overcrowding, type 1 and type 2 diabetes, substance misuse, HIV, food insecurity and malnutrition, and smoking on the burden of tuberculosis. We aimed to understand the potential contribution of such determinants to tuberculosis in Indigenous peoples and to document steps taken to address them. METHODS: We did a systematic review using seven databases (MEDLINE, Embase, CINAHL, Global Health, BIOSIS Previews, Web of Science, and the Cochrane Library). We identified English language articles published from Jan 1, 1980, to Dec 20, 2017, reporting the prevalence of proximate determinants of tuberculosis and preventive programmes targeting these determinants in Indigenous communities worldwide. We included any randomised controlled trials, controlled studies, cohort studies, cross-sectional studies, case reports, and qualitative research. Exclusion criteria were articles in languages other than English, full text not available, population was not Indigenous, focused exclusively on children or older people, and studies that focused on pharmacological interventions. FINDINGS: Of 34 255 articles identified, 475 were eligible for inclusion. Most studies confirmed a higher prevalence of proximate determinants in Indigenous communities than in the general population. Diabetes was more frequent in Indigenous communities within high-income countries versus in low-income countries. The prevalence of alcohol use was generally similar to that among non-Indigenous groups, although patterns of drinking often differed. Smoking prevalence and smokeless tobacco consumption were commonly higher in Indigenous groups than in non-Indigenous groups. Food insecurity was highly prevalent in most Indigenous communities evaluated. Substance use was more frequent in Indigenous inhabitants of high-income countries than of low-income countries, with wide variation across Indigenous communities. The literature pertaining to HIV, crowding, and housing conditions among Indigenous peoples was too scant to draw firm conclusions. Preventive programmes that are culturally appropriate targeting these determinants appear feasible, although their effectiveness is largely unproven. INTERPRETATION: Indigenous peoples were generally reported to have a higher prevalence of several proximate determinants of tuberculosis than non-Indigenous peoples, with wide variation across Indigenous communities. These findings emphasise the need for community-led, culturally appropriate strategies to address smoking, food insecurity, and diabetes in Indigenous populations as important public health goals in their own right, and also to reduce the burden of tuberculosis. FUNDING: Canadian Institutes of Health Research.


Assuntos
Saúde Global/estatística & dados numéricos , Grupos Populacionais/estatística & dados numéricos , Tuberculose/epidemiologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
9.
Eur Respir J ; 52(5)2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30166325

RESUMO

Ensuring adherence and support during treatment of tuberculosis (TB) is a major public health challenge. Digital health technologies could help improve treatment outcomes. We considered their potential cost and impact on treatment for active or latent TB in Brazil.Decision analysis models simulated two adult cohorts with 1) drug-susceptible active TB, and 2) multidrug-resistant TB, and two cohorts treated with isoniazid for latent TB infection (LTBI): 1) close contacts of persons with active TB, and 2) others newly diagnosed with LTBI. We evaluated four digital support strategies: two different medication monitors, synchronous video-observed therapy (VOT), and two-way short message service (SMS). Comparators were standard directly observed treatment for active TB and self-administered treatment for LTBI. Projected outcomes included costs (2016 US dollars), plus active TB cases and disability-adjusted life years averted among persons with LTBI.For individuals with active TB, medication monitors and VOT are projected to lead to substantial (up to 58%) cost savings, in addition to alleviating inconvenience and cost to patients of supervised treatment visits. For LTBI treatment, SMS and medication monitors are projected to be the most cost-effective interventions. However, all projections are limited by the scarcity of published estimates of clinical effect for the digital technologies.


Assuntos
Antituberculosos/uso terapêutico , Redução de Custos , Tuberculose Latente/economia , Telemedicina/economia , Mensagem de Texto/economia , Tuberculose/economia , Adulto , Brasil , Terapia Diretamente Observada , Feminino , Humanos , Isoniazida/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Masculino , Resultado do Tratamento , Tuberculose/tratamento farmacológico
10.
N Engl J Med ; 379(5): 454-463, 2018 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-30067928

RESUMO

BACKGROUND: The treatment of latent infection with Mycobacterium tuberculosis is important in children because of their vulnerability to life-threatening forms of tuberculosis disease. The current standard treatment - 9 months of isoniazid - has been associated with poor adherence and toxic effects, which have hampered the effectiveness of the drug. In adults, treatment with 4 months of rifampin has been shown to be safer and to have higher completion rates than 9 months of isoniazid. METHODS: In this multicenter, open-label trial, we randomly assigned 844 children (<18 years of age) with latent M. tuberculosis infection to receive either 4 months of rifampin or 9 months of isoniazid. The primary outcome was adverse events of grade 1 to 5 that resulted in the permanent discontinuation of a trial drug. Secondary outcomes were treatment adherence, side-effect profile, and efficacy. Independent review panels whose members were unaware of trial-group assignments adjudicated all adverse events and progression to active tuberculosis. RESULTS: Of the children who underwent randomization, 829 were eligible for inclusion in the modified intention-to-treat analysis. A total of 360 of 422 children (85.3%) in the rifampin group completed per-protocol therapy, as compared with 311 of 407 (76.4%) in the isoniazid group (adjusted difference in the rates of treatment completion, 13.4 percentage points; 95% confidence interval [CI], 7.5 to 19.3). There were no significant between-group differences in the rates of adverse events, with fewer than 5% of the children in the combined groups with grade 1 or 2 adverse events that were deemed to be possibly related to a trial drug. Active tuberculosis, including 1 case with resistance to isoniazid, was diagnosed in 2 children in the isoniazid group during 542 person-years of follow-up, as compared with no cases in the rifampin group during 562 person-years (rate difference, -0.37 cases per 100 person-years; 95% CI, -0.88 to 0.14). CONCLUSIONS: Among children under the age of 18 years, treatment with 4 months of rifampin had similar rates of safety and efficacy but a better rate of adherence than 9 months of treatment with isoniazid. (Funded by the Canadian Institutes of Health Research and Conselho Nacional de Pesquisa; ClinicalTrials.gov number, NCT00170209 .).


Assuntos
Antibióticos Antituberculose/administração & dosagem , Antibióticos Antituberculose/efeitos adversos , Isoniazida/administração & dosagem , Isoniazida/efeitos adversos , Tuberculose Latente/tratamento farmacológico , Rifampina/administração & dosagem , Rifampina/efeitos adversos , Adolescente , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Seguimentos , Humanos , Lactente , Análise de Intenção de Tratamento , Masculino , Adesão à Medicação , Segurança do Paciente , Resultado do Tratamento
11.
N Engl J Med ; 379(5): 440-453, 2018 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-30067931

RESUMO

BACKGROUND: A 9-month regimen of isoniazid can prevent active tuberculosis in persons with latent tuberculosis infection. However, the regimen has been associated with poor adherence rates and with toxic effects. METHODS: In an open-label trial conducted in nine countries, we randomly assigned adults with latent tuberculosis infection to receive treatment with a 4-month regimen of rifampin or a 9-month regimen of isoniazid for the prevention of confirmed active tuberculosis within 28 months after randomization. Noninferiority and potential superiority were assessed. Secondary outcomes included clinically diagnosed active tuberculosis, adverse events of grades 3 to 5, and completion of the treatment regimen. Outcomes were adjudicated by independent review panels. RESULTS: Among the 3443 patients in the rifampin group, confirmed active tuberculosis developed in 4 and clinically diagnosed active tuberculosis developed in 4 during 7732 person-years of follow-up, as compared with 4 and 5 patients, respectively, among 3416 patients in the isoniazid group during 7652 person-years of follow-up. The rate differences (rifampin minus isoniazid) were less than 0.01 cases per 100 person-years (95% confidence interval [CI], -0.14 to 0.16) for confirmed active tuberculosis and less than 0.01 cases per 100 person-years (95% CI, -0.23 to 0.22) for confirmed or clinically diagnosed tuberculosis. The upper boundaries of the 95% confidence interval for the rate differences of the confirmed cases and for the confirmed or clinically diagnosed cases of tuberculosis were less than the prespecified noninferiority margin of 0.75 percentage points in cumulative incidence; the rifampin regimen was not superior to the isoniazid regimen. The difference in the treatment-completion rates was 15.1 percentage points (95% CI, 12.7 to 17.4). The rate differences for adverse events of grade 3 to 5 occurring within 146 days (120% of the 4-month planned duration of the rifampin regimen) were -1.1 percentage points (95% CI, -1.9 to -0.4) for all events and -1.2 percentage points (95% CI, -1.7 to -0.7) for hepatotoxic events. CONCLUSIONS: The 4-month regimen of rifampin was not inferior to the 9-month regimen of isoniazid for the prevention of active tuberculosis and was associated with a higher rate of treatment completion and better safety. (Funded by the Canadian Institutes of Health Research and the Australian National Health and Medical Research Council; ClinicalTrials.gov number, NCT00931736 .).


Assuntos
Antibióticos Antituberculose/administração & dosagem , Isoniazida/administração & dosagem , Tuberculose Latente/tratamento farmacológico , Rifampina/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antituberculose/efeitos adversos , Esquema de Medicação , Feminino , Seguimentos , Humanos , Isoniazida/efeitos adversos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Rifampina/efeitos adversos
13.
Eur Respir Rev ; 27(148)2018 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-29769294

RESUMO

Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc). We performed a systematic review to characterise the use and validation of pulmonary function tests (PFTs) as surrogate markers for systemic sclerosis-associated interstitial lung disease (SSc-ILD) progression.Five electronic databases were searched to identify all relevant studies. Included studies either used at least one PFT measure as a longitudinal outcome for SSc-ILD progression (i.e. outcome studies) and/or reported at least one classical measure of validity for the PFTs in SSc-ILD (i.e. validation studies).This systematic review included 169 outcome studies and 50 validation studies. Diffusing capacity of the lung for carbon monoxide (DLCO) was cumulatively the most commonly used outcome until 2010 when it was surpassed by forced vital capacity (FVC). FVC (% predicted) was the primary endpoint in 70.4% of studies, compared to 11.3% for % predicted DLCO Only five studies specifically aimed to validate the PFTs: two concluded that DLCO was the best measure of SSc-ILD extent, while the others did not favour any PFT. These studies also showed respectable validity measures for total lung capacity (TLC).Despite the current preference for FVC, available evidence suggests that DLCO and TLC should not yet be discounted as potential surrogate markers for SSc-ILD progression.


Assuntos
Doenças Pulmonares Intersticiais/diagnóstico , Pulmão/fisiopatologia , Testes de Função Respiratória , Escleroderma Sistêmico/complicações , Biópsia , Progressão da Doença , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Doenças Pulmonares Intersticiais/terapia , Valor Preditivo dos Testes , Prognóstico , Capacidade de Difusão Pulmonar , Reprodutibilidade dos Testes , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/fisiopatologia , Escleroderma Sistêmico/terapia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Capacidade Pulmonar Total , Capacidade Vital
14.
Ann Am Thorac Soc ; 15(5): 570-580, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29393655

RESUMO

RATIONALE: Data are limited regarding the safety of 12-dose once-weekly isoniazid (H, 900 mg) plus rifapentine (P, 900 mg) (3HP) for latent infection treatment during pregnancy. OBJECTIVES: To assess safety and pregnancy outcomes among pregnant women who were inadvertently exposed to study medications in two latent tuberculosis infection trials (PREVENT TB or iAdhere) evaluating 3HP and 9 months of daily isoniazid (H, 300 mg) (9H). METHODS: Data from reproductive-age (15-51 yr) women who received one or more study dose of 3HP or 9H in either trial were analyzed. Drug exposure during pregnancy occurred if the estimated date of conception was on or before the last dose date. RESULTS: Of 126 pregnancies (125 participants) that occurred during treatment or follow-up, 87 were exposed to study drugs. Among these, fetal loss was reported for 4/31 (13%) and 8/56 (14%), 3HP and 9H, respectively (difference, 13% - 14% = -1%; 95% confidence interval = -17% to +18%) and congenital anomalies in 0/20 and 2/41 (5%) live births, 3HP and 9H, respectively (difference, 0% - 5% = -5%; 95% confidence interval = -18% to +16%). All fetal losses occurred in pregnancies of less than 20 weeks. Of the total 126 pregnancies, fetal loss was reported in 8/54 (15%) and 9/72 (13%), 3HP and 9H, respectively; and congenital anomalies in 1/37 (3%) and 2/56 (4%) live births, 3HP and 9H, respectively. The overall proportion of fetal loss (17/126 [13%]) and anomalies (3/93 [3%]) were similar to those estimated for the United States, 17% and 3%, respectively. CONCLUSIONS: Among reported pregnancies in these two latent tuberculosis infection trials, there was no unexpected fetal loss or congenital anomalies. These data offer some preliminary reassurance to clinicians and patients in circumstances when these drugs and regimens are the best option in pregnancy or in women of child-bearing potential. This work used the identifying trial registration numbers NCT00023452 and NCT01582711, corresponding to the primary clinical trials PREVENT TB and iAdhere (Tuberculosis Trials Consortium Study 26 and 33).


Assuntos
Isoniazida/administração & dosagem , Tuberculose Latente/tratamento farmacológico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Rifampina/análogos & derivados , Adolescente , Adulto , Antituberculosos/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Recém-Nascido , Pessoa de Meia-Idade , Gravidez , Resultado da Gravidez , Rifampina/administração & dosagem , Adulto Jovem
15.
Eur Respir J ; 51(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29326332

RESUMO

Digital technologies are increasingly harnessed to support treatment of persons with tuberculosis (TB). Since in-person directly observed treatment (DOT) can be resource intensive and challenging to implement, these technologies may have the potential to improve adherence and clinical outcomes. We reviewed the effect of these technologies on TB treatment adherence and patient outcomes.We searched several bibliographical databases for studies reporting the effect of digital interventions, including short message service (SMS), video-observed therapy (VOT) and medication monitors (MMs), to support treatment for active TB. Only studies with a control group and which reported effect estimates were included.Four trials showed no statistically significant effect on treatment completion when SMS was added to standard care. Two observational studies of VOT reported comparable treatment completion rates when compared with in-person DOT. MMs increased the probability of cure (RR 2.3, 95% CI 1.6-3.4) in one observational study, and one trial reported a statistically significant reduction in missed treatment doses relative to standard care (adjusted means ratio 0.58, 95% CI 0.42-0.79).Evidence of the effect of digital technologies to improve TB care remains limited. More studies of better quality are needed to determine how such technologies can enhance programme performance.


Assuntos
Tecnologia Biomédica/métodos , Terapia Diretamente Observada , Adesão à Medicação , Mensagem de Texto , Tuberculose Pulmonar/terapia , Telefone Celular , Comunicação , Humanos , Estudos Observacionais como Assunto , Valor Preditivo dos Testes , Pneumologia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Resultado do Tratamento
16.
BMC Pulm Med ; 17(1): 178, 2017 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-29216855

RESUMO

BACKGROUND: Guidelines recommend timely evaluation of patients with suspected lung cancer. We evaluated the impact of a Rapid Investigation Clinic (RIC) on timeliness of lung cancer diagnosis and treatment between February 2010 and December 2011. METHODS: Investigation within the RIC was conducted by a pulmonologist and a nurse clinician. Controls were patients with lung cancer, investigated outside the RIC at the same institution during the same time period. The primary outcome was time between first contact with a local physician for suspected lung cancer (T0) and first treatment. Factors associated with the delay from T0 to first treatment were examined using multivariate analysis. Completeness of lung cancer staging according to guidelines was assessed. RESULTS: A total of 195 patients were investigated within the RIC vs. 132 patients outside the RIC. The median delay between T0 and first treatment was 65 days (interquartile range [IQR] 46-92 days) in the RIC and 78 days (IQR 49-119 days) in the non-RIC patients (p ≤ 0.01). Time from T0 to pathological diagnosis was shorter in the RIC (median 26 days; IQR 14-42 days) vs. non-RIC patients (median 40 days; IQR 16-68 days). In multivariate analysis, investigation in the RIC was associated with a reduction in time to first treatment of 24 days (95% confidence interval [CI] 12-35 days) when adjusted for relevant confounders. Guideline-concordant investigation occurred more frequently in RIC patients, based on the quality indicators examined. CONCLUSIONS: A Rapid Investigation Clinic reduces delays to lung cancer diagnosis and treatment, and impacts quality of care.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Diagnóstico Tardio/estatística & dados numéricos , Assistência à Saúde/organização & administração , Neoplasias Pulmonares/diagnóstico , Encaminhamento e Consulta , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Tempo para o Tratamento/estatística & dados numéricos , Idoso , Biópsia por Agulha , Broncoscopia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Endossonografia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Mediastinoscopia , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Enfermeiras Clínicas , Pneumologistas , Qualidade da Assistência à Saúde , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/terapia , Fatores de Tempo
17.
BMC Med ; 15(1): 104, 2017 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-28514962

RESUMO

BACKGROUND: In North America, tuberculosis incidence is now very low and risk to healthcare workers has fallen. Indeed, recent cohort data question routine annual tuberculosis screening in this context. We compared the cost-effectiveness of three potential strategies for ongoing screening of North American healthcare workers at risk of exposure. The analysis did not evaluate the cost-effectiveness of screening at hiring, and considered only workers with negative baseline tests. METHODS: A decision analysis model simulated a hypothetical cohort of 1000 workers following negative baseline tests, considering duties, tuberculosis exposure, testing and treatment. Two tests were modelled, the tuberculin skin test (TST) and QuantiFERON®-TB-Gold In-Tube (QFT). Three screening strategies were compared: (1) annual screening, where workers were tested yearly; (2) targeted screening, where workers with high-risk duties (e.g. respiratory therapy) were tested yearly and other workers only after recognised exposure; and (3) post exposure-only screening, where all workers were tested only after recognised exposure. Workers with high-risk duties had 1% annual risk of infection, while workers with standard patient care duties had 0.3%. In an alternate higher-risk scenario, the corresponding annual risks of infection were 3% and 1%, respectively. We projected costs, morbidity, quality-adjusted survival and mortality over 20 years after hiring. The analysis used the healthcare system perspective and a 3% annual discount rate. RESULTS: Over 20 years, annual screening with TST yielded an expected 2.68 active tuberculosis cases/1000 workers, versus 2.83 for targeted screening and 3.03 for post-exposure screening only. In all cases, annual screening was associated with poorer quality-adjusted survival, i.e. lost quality-adjusted life years, compared to targeted or post-exposure screening only. The annual TST screening strategy yielded an incremental cost estimate of $1,717,539 per additional case prevented versus targeted TST screening, which in turn cost an incremental $426,678 per additional case prevented versus post-exposure TST screening only. With the alternate "higher-risk" scenario, the annual TST strategy cost an estimated $426,678 per additional case prevented versus the targeted TST strategy, which cost an estimated $52,552 per additional case prevented versus post-exposure TST screening only. In all cases, QFT was more expensive than TST, with no or limited added benefit. Sensitivity analysis suggested that, even with limited exposure recognition, annual screening was poorly cost-effective. CONCLUSIONS: For most North American healthcare workers, annual tuberculosis screening appears poorly cost-effective. Reconsideration of screening practices is warranted.


Assuntos
Pessoal de Saúde , Tuberculose Latente/diagnóstico , Adulto , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Feminino , Humanos , Incidência , Tuberculose Latente/economia , Tuberculose Latente/epidemiologia , Masculino , Programas de Rastreamento/economia , Anos de Vida Ajustados por Qualidade de Vida , Teste Tuberculínico
18.
BMC Infect Dis ; 16(1): 679, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27846812

RESUMO

BACKGROUND: Hospitalization is the most costly health system component of tuberculosis (TB) control programs. Our objectives were to identify how frequently patients are hospitalized, and the factors associated with hospitalizations and length-of-stay (LOS) of TB patients in a large Canadian city. METHODS: We extracted data from the Montreal TB Resource database, a retrospective cohort of all active TB cases reported to the Montreal Public Health Department between January 1996 and May 2007. Data included patient demographics, clinical characteristics, and dates of treatment and hospitalization. Predictors of hospitalization and LOS were estimated using logistic regression and Cox proportional hazards regression, respectively. RESULTS: There were 1852 active TB patients. Of these, 51% were hospitalized initially during the period of diagnosis and/or treatment initiation (median LOS 17.5 days), and 9.0% hospitalized later during treatment (median LOS 13 days). In adjusted models, patients were more likely to be hospitalized initially if they were children, had co-morbidities, smear-positive symptomatic pulmonary TB, cavitary or miliary TB, and multi- or poly-TB drug resistance. Factors predictive of longer initial LOS included having HIV, renal disease, symptomatic pulmonary smear-positive TB, multi- or poly-TB drug resistance, and being in a teaching hospital. CONCLUSIONS: We found a high hospitalization rate during diagnosis and treatment of patients with TB. Diagnostic delay due to low index of suspicion may result in patients presenting with more severe disease at the time of diagnosis. Earlier identification and treatment, through interventions to increase TB awareness and more targeted prevention programs, might reduce costly TB-related hospital use.


Assuntos
Hospitalização/estatística & dados numéricos , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Comorbidade , Diagnóstico Tardio , Feminino , Humanos , Lactente , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Quebeque/epidemiologia , Quebeque/etnologia , Estudos Retrospectivos , Tuberculose/epidemiologia , Tuberculose Miliar/diagnóstico , Tuberculose Miliar/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Adulto Jovem
19.
PLoS One ; 11(5): e0154825, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27149116

RESUMO

BACKGROUND: In countries with low tuberculosis (TB) incidence, immigrants from higher incidence countries represent the major pool of individuals with latent TB infection (LTBI). The antenatal period represents an opportunity for immigrant women to access the medical system, and hence for potential screening and treatment of LTBI. However, such screening and treatment during pregnancy remains controversial. OBJECTIVES: In order to further understand the prevalence, natural history, screening and management of LTBI in pregnancy, we conducted a systematic literature review addressing the screening and treatment of LTBI, in pregnant women without known HIV infection. METHODS: A systematic review of 4 databases (Embase, Embase Classic, Medline, Cochrane Library) covering articles published from January 1st 1980 to April 30th 2014. Articles in English, French or Spanish with relevant information on prevalence, natural history, screening tools, screening strategies and treatment of LTBI during pregnancy were eligible for inclusion. Articles were excluded if (1) Full text was not available (2) they were case series or case studies (3) they focused exclusively on prevalence, diagnosis and treatment of active TB (4) the study population was exclusively HIV-infected. RESULTS: Of 4,193 titles initially identified, 208 abstracts were eligible for review. Of these, 30 articles qualified for full text review and 22 were retained: 3 cohort studies, 2 case-control studies, and 17 cross-sectional studies. In the USA, the estimated prevalence of LTBI ranged from 14 to 48% in women tested, and tuberculin skin test (TST) positivity was associated with ethnicity. One study suggested that incidence of active TB was significantly increased during the 180 days postpartum (Incidence rate ratio, 1.95 (95% CI 1.24-3.07). There was a high level of adherence with both skin testing (between 90-100%) and chest radiography (93-100%.). In three studies from low incidence settings, concordance between TST and an interferon-gamma release assay was 77, 88 and 91% with kappa values ranging from 0.26 to 0.45. In low incidence settings, an IGRA may be more specific and less sensitive than TST, and results do not appear to be altered by pregnancy. The proportion of women who attended follow-up visits after positive tuberculin tests varied from 14 to 69%, while 5 to 42% of those who attended follow-up visits completed a minimum of 6 months of isoniazid treatment. One study raised the possibility of an association of pregnancy/post-partum state with INH hepatitis (risk ratio 2,5, 95% CI 0.8-8.2) and fatal hepatotoxicity (rate ratio 4.0, 95% CI 0.2-258). One study deemed INH safe during breastfeeding based on peak concentrations in plasma and breast milk after INH administration. CONCLUSION: Pregnancy is an opportunity to screen for LTBI. Interferon-gamma release assays are likely comparable to tuberculin skin tests and may be used during pregnancy. Efforts should be made to improve adherence with follow-up and treatment post-partum. Further data are needed with respect to safety and feasibility of antepartum INH therapy, and with respect to alternative treatment regimens.


Assuntos
Tuberculose Latente/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Antituberculosos/uso terapêutico , Feminino , Humanos , Tuberculose Latente/complicações , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Prevalência
20.
Thorax ; 71(8): 719-25, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27084956

RESUMO

OBJECTIVE: It is unclear whether objectively measured maternal sleep-disordered breathing (SDB) leads to poor fetal outcomes. In this study, we prospectively assessed whether polysomnography-based diagnosis of SDB in the third trimester is associated with the delivery of small for gestational age (SGA) infants. STUDY DESIGN: Participants were recruited from a multicentre pregnancy cohort study. Eligible participants were evaluated for SDB based on symptoms (snoring and/or witnessed apnoeas assessed using the Pittsburgh Sleep Quality Index questionnaire) and in-home complete polysomnography in the third trimester. SGA was defined as <10th centile using customised birthweight centiles adjusted for maternal parity, prepregnancy body mass index (BMI), ethnicity, gestational age and infant sex. RESULTS: Of the 234 pregnant participants who completed a sleep study, 82% were Caucasian, with mean (SD) age of 31 (4.3) years and a prepregnancy BMI of 23 (4) kg/m(2). The delivery of SGA infants occurred in 27 (12%) of the study participants. The symptoms of SDB had poor overall sensitivity and specificity for diagnosing SDB identified by polysomnography. Symptoms of SDB in the third trimester demonstrated a potential association with delivering an SGA infant, however this did not reach statistical significance (OR 2.36 (95% CI 0.85 to 6.54, p=0.10)). However, the odds of delivering an SGA infant were significantly increased with polysomnography-based diagnosis of maternal SDB (using apnoea-hypopnoea index cut-off of 10, OR 2.65 (95% CI 1.15 to 6.10, p=0.02)). CONCLUSIONS: Objectively measured SDB in the third trimester is significantly associated with the delivery of SGA infants.


Assuntos
Recém-Nascido Pequeno para a Idade Gestacional , Adulto , Peso ao Nascer , Índice de Massa Corporal , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Ontário , Polissonografia , Valor Preditivo dos Testes , Gravidez , Complicações na Gravidez/epidemiologia , Terceiro Trimestre da Gravidez , Estudos Prospectivos , Quebeque , Fatores de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/diagnóstico , Inquéritos e Questionários
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