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Confounding by indication is a key challenge for pharmacoepidemiologists. Although self-controlled study designs address time-invariant confounding, indications sometimes vary over time. For example, infection might act as a time-varying confounder in a study of antibiotics and uveitis, because it is time-limited and a direct cause both of receiving antibiotics and uveitis. Methods for incorporating active comparators in self-controlled studies to address such time-varying confounding by indication have only recently been developed. In this paper we formalize these methods, and provide a detailed description for how the active comparator rate ratio can be derived in a self-controlled case series (SCCS): either by explicitly comparing the regression coefficients for a drug of interest and an active comparator under certain circumstances using a simple ratio approach, or through the use of a nested regression model. The approaches are compared in two case studies, one examining the association between thiazolidinediones and fractures, and one examining the association between fluoroquinolones and uveitis using the UK Clinical Practice Research DataLink. Finally, we provide recommendations for the use of these methods, which we hope will support the design, execution and interpretation of SCCS using active comparators and thereby increase the robustness of pharmacoepidemiological studies.
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RATIONALE: Longitudinal epidemiological and clinical data are needed to improve the management of patients with bronchiectasis developing nontuberculous mycobacterial (NTM) pulmonary disease. OBJECTIVES: To describe the epidemiology, patient management, and treatment outcomes of NTM infections in patients with bronchiectasis enrolled in the United States Bronchiectasis and NTM Research Registry (US BRR). METHODS: This was a retrospective cohort study of patients with bronchiectasis and NTM infections enrolled with follow-up in the US BRR in 2008-2019. The study included patients with ≥1 positive NTM respiratory culture in the 24-month baseline period (baseline NTM cohort) and/or during the annual follow-up visits (incident NTM cohort). Incidence, prevalence, baseline patient characteristics, treatment exposure, treatment outcomes, and respiratory clinical outcomes were described in the baseline NTM cohort, incident NTM cohort, and both cohorts combined (prevalent NTM cohort). RESULTS: Between 2008 and 2019, 37.9% (1457/3840) of patients with bronchiectasis in the US BRR met the inclusion criteria for this study and were reported to have Mycobacterium avium complex (MAC) and/or Mycobacterium abscessus complex (MABSC) infections. MAC prevalence increased steadily in the US BRR during 2009-2019; incidence was relatively stable, except for a peak in 2011 followed by a slow decrease. MABSC and mixed MAC/MABSC infections were rare. Most patients with bronchiectasis and NTM infections in the registry were female, White, and aged >65 years. The antibiotics administered most commonly reflected current guidelines. In the prevalent cohort, 44.9% of MAC infections and 37.1% of MABSC infections remained untreated during follow-up, and MAC treatment was initiated with delay (>90 days after positive NTM respiratory culture) twice as frequently as promptly (≤90 days after positive NTM respiratory culture) (68.6% vs 31.4%, respectively). The median time from diagnosis to treatment was shorter for MABSC versus MAC infections (194.0 days [interquartile range (IQR) 8.0, 380.0] vs 296.0 days [IQR 35.0, 705.0], respectively). Among patients with MAC infections who completed treatment, 27.6% were classified as cured and 29.6% as treatment failure during the annual follow-up visit window. For MABSC, these proportions were 25.0% and 28.0%, respectively. CONCLUSIONS: A considerable proportion of MAC and MABSC infections were untreated or treated after initial delay/observation. MABSC infections were more likely to be treated and start treatment sooner than MAC infections. Further longitudinal studies are warranted to evaluate the monitor-with-delay approach and inform clinical guidelines.
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Bronquiectasia , Infecções por Mycobacterium não Tuberculosas , Humanos , Feminino , Masculino , Estudos Retrospectivos , Estudos de Coortes , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas , Complexo Mycobacterium avium , Bronquiectasia/tratamento farmacológico , Bronquiectasia/epidemiologia , Bronquiectasia/microbiologia , Sistema de RegistrosRESUMO
PURPOSE: Prevalent new user (PNU) designs extend the active comparator new user design by allowing for the inclusion of initiators of the study drug who were previously on a comparator treatment. We performed a literature review summarising current practice. METHODS: PubMed was searched for studies applying the PNU design since its proposal in 2017. The review focused on three components. First, we extracted information on the overall study design, including the database used. We summarised information on implementation of the PNU design, including key decisions relating to exposure set definition and estimation of time-conditional propensity scores. Finally, we reviewed the analysis strategy of the matched cohort. RESULTS: Nineteen studies met the criteria for inclusion. Most studies (73%) implemented the PNU design in electronic health record or registry databases, with the remaining using insurance claims databases. Of 15 studies including a class of prevalent users, 40% deviated from the original exposure set definition proposals in favour of a more complex definition. Four studies did not include prevalent new users but used other aspects of the PNU framework. Several studies lacked details on exposure set definition (n = 2), time-conditional propensity score model (n = 2) or integration of complex analytical techniques, such as the high-dimensional propensity score algorithm (n = 3). CONCLUSION: PNU designs have been applied in a range of therapeutic and disease areas. However, to encourage more widespread use of this design and help shape best practice, there is a need for improved accessibility, specifically through the provision of analytical code alongside guidance to support implementation and transparent reporting.
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Algoritmos , Projetos de Pesquisa , HumanosRESUMO
High body mass index (BMI) is paradoxically associated with better outcome in hemodialysis (HD) patients. Persistent inflammation commonly features in clinical conditions where the obesity paradox is described. We examined the relationship between BMI and mortality in HD patients, accounting for inflammation, in a historic cohort study of 5904 incident HD patients enrolled in 2007-2009 (312 facilities; 15 European countries) with ≥3 months of follow-up. Patients were classified by presence (n=3231) or absence (n=2673) of inflammation (C-reactive protein ≥10 mg/l and/or albumin ≤35 g/l). Patients were divided into quintiles by BMI (Q1-Q5: <21.5, 21.5-24.0, >24.0-26.4, >26.4-29.8, and >29.8 kg/m(2), respectively). Noninflamed patients in BMI Q5 formed the reference group. During a median follow-up period of 36.7 months, 1929 deaths occurred (822 cardiovascular), with 655 patients censored for renal transplantation and 1183 for loss to follow-up. Greater mortality was observed in inflamed patients (P<0.001). In fully adjusted time-dependent analyses, the all-cause mortality risk in noninflamed patients was higher only in the lowest BMI quintile (hazard ratio [HR, 1.80; 95% confidence interval [95% CI], 1.26 to 2.56). No protective effect was associated with higher BMI quintiles in noninflamed patients. Conversely, higher BMI associated with lower all-cause mortality risk in inflamed patients (HR [95% CI] for Q1: 5.63 [4.25 to 7.46]; Q2: 3.88 [2.91 to 5.17]; Q3: 2.89 [2.16 to 3.89]; Q4: 2.14 [1.59 to 2.90]; and Q5: 1.77 [1.30 to 2.40]). Thus, whereas a protective effect of high BMI was observed in inflamed patients, this effect was mitigated in noninflamed patients.
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Índice de Massa Corporal , Inflamação , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Diálise Renal/mortalidade , Causas de Morte , Estudos de Coortes , Humanos , Inflamação/complicações , Falência Renal Crônica/complicações , Obesidade/complicações , RiscoRESUMO
Although mortality risk scores for chronic hemodialysis (HD) patients should have an important role in clinical decision-making, those currently available have limited applicability, robustness, and generalizability. Here we applied a modified Framingham Heart Study approach to derive 1- and 2-year all-cause mortality risk scores using a 11,508 European incident HD patient database (AROii) recruited between 2007 and 2009. This scoring model was validated externally using similar-sized Dialysis Outcomes and Practice Patterns Survey (DOPPS) data. For AROii, the observed 1- and 2-year mortality rates were 13.0 (95% confidence interval (CI; 12.3-13.8)) and 11.2 (10.4-12.1)/100 patient years, respectively. Increasing age, low body mass index, history of cardiovascular disease or cancer, and use of a vascular access catheter during baseline were consistent predictors of mortality. Among baseline laboratory markers, hemoglobin, ferritin, C-reactive protein, serum albumin, and creatinine predicted death within 1 and 2 years. When applied to the DOPPS population, the predictive risk score models were highly discriminatory, and generalizability remained high when restricted by incidence/prevalence and geographic location (C-statistics 0.68-0.79). This new model offers improved predictive power over age/comorbidity-based models and also predicted early mortality (C-statistic 0.71). Our new model delivers a robust and reproducible mortality risk score, based on readily available clinical and laboratory data.
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Falência Renal Crônica/mortalidade , Diálise Renal/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de RiscoRESUMO
Early mortality is high in hemodialysis (HD) patients, but little is known about early cardiovascular event (CVE) rates after HD initiation. To study this we analyzed data in the AROii cohort of incident HD patients from over 300 European Fresenius Medical Care dialysis centers. Weekly rates of a composite of CVEs during the first year and monthly rates of the composite and its constituents (coronary artery, cerebrovascular, peripheral arterial, congestive heart failure, and sudden cardiac death) during the first 2 years after HD initiation were assessed. Of 6308 patients that started dialysis within 7 days, 1449 patients experienced 2405 CVEs over the next 2 years. The first-year CVE rate (30.2/100 person-years; 95% CI, 28.7-31.7) greatly exceeded the second-year rate (19.4/100; 95% CI, 18.1-20.8). Composite CVEs were highest during the first week with increased risk compared with the second year, persisting until the fifth month. Except for sudden cardiac death, temporal patterns of rates for all CVE categories were very similar, with highest rates during the first month and a high-risk period extending to 4 months. Higher or lower cumulative weekly dialysis dose, lower blood flow, and lower net ultrafiltration during dialysis were associated with CVE during the high-risk period, but not during the post high-risk period. Thus, the incidence of CVE in the first weeks after HD initiation is much higher than during subsequent periods which raises concerns that HD initiation may trigger CVEs.
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Doenças Cardiovasculares/epidemiologia , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/terapia , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/etiologia , Doença das Coronárias/epidemiologia , Morte Súbita Cardíaca/epidemiologia , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/epidemiologia , Insuficiência Renal Crônica/complicações , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Fatores de TempoRESUMO
PURPOSE: Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is clinically and economically important in the treatment of anaemia in chronic kidney disease (CKD) patients. Previous studies focused on baseline predictors of ESA hyporesponsiveness, rather than factors associated with the transition to this state. Reversibility of ESA hyporesponsiveness has also not been studied previously. METHODS: Case-crossover methodology was applied to a cohort of 6645 European CKD patients undergoing haemodialysis and prescribed ESAs. Ninety-day ESA exposure periods were defined, haemoglobin (Hb) response was calculated using the last 30 days of one period and the first 30 days of the next, and periods were classified based on a median ESA dose (80.8 IU/kg/week) and a 10 g/dL Hb threshold. Clinical, dialysis and laboratory data from patients' first hyporesponsive 'case' period was compared with the preceding responsive 'control' period using conditional logistic regression. A similar approach was applied to hyporesponsiveness reversal. RESULTS: Of the patients, 672 experienced hyporesponsiveness periods with preceding responsive periods; 711 reversed to normality from hyporesponsiveness periods. Transition to hyporesponsiveness was associated with hospitalization, vascular access changes or worsening inflammation, with these factors accounting for over two-thirds of transitions. Findings were largely insensitive to alternative ESA doses and Hb thresholds. Continued hospitalization, catheter insertion and uncontrolled secondary hyperparathyroidism were associated with a lack of regain of responsiveness. CONCLUSIONS: Transition to hyporesponsiveness is linked to the development of conditions such as hospitalization events, vascular access issues or episodes of systemic inflammation. However, a third of hyporesponsive episodes remain unexplained.
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Anemia/tratamento farmacológico , Hematínicos/uso terapêutico , Diálise Renal , Estudos de Coortes , Estudos Cross-Over , Relação Dose-Resposta a Droga , Europa (Continente) , Humanos , Modelos Logísticos , Análise Multivariada , Fatores de RiscoRESUMO
PURPOSE: The generalisability of randomised controlled trials (RCTs) may be limited by restrictive entry criteria or by their experimental nature. Observational research can provide complementary findings but is prone to bias. Employing propensity score matching, to reduce such bias, we compared the real-life effect of cinacalcet use on all-cause mortality (ACM) with findings from the Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE) RCT in chronic haemodialysis patients. METHODS: Incident adult haemodialysis patients receiving cinacalcet, recruited in a prospective observational cohort from 2007-2009 (AROii; n = 10,488), were matched to non-exposed patients regardless of future exposure status. The effect of treatment crossover was investigated with inverse probability of censoring weighted and lag-censored analyses. EVOLVE ACM data were analysed largely as described for the primary composite endpoint. RESULTS: AROii patients receiving cinacalcet (n = 532) were matched to 1790 non-exposed patients. The treatment effect of cinacalcet on ACM in the main AROii analysis (hazard ratio 1.03 [95% confidence interval (CI) 0.78-1.35]) was closer to the null than for the Intention to Treat (ITT) analysis of EVOLVE (0.94 [95%CI 0.85-1.04]). Adjusting for non-persistence by 0- and 6-month lag-censoring and by inverse probability of censoring weight, the hazard ratios in AROii (0.76 [95%CI 0.51-1.15], 0.84 [95%CI 0.60-1.18] and 0.79 [95%CI 0.56-1.11], respectively) were comparable with those of EVOLVE (0.82 [95%CI 0.67-1.01], 0.83 [95%CI 0.73-0.96] and 0.87 [95%CI 0.71-1.06], respectively). CONCLUSIONS: Correcting for treatment crossover, we observed results in the 'real-life' setting of the AROii observational cohort that closely mirrored the results of the EVOLVE RCT. Persistence-corrected analyses revealed a trend towards reduced ACM in haemodialysis patients receiving cinacalcet therapy.
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Calcimiméticos/uso terapêutico , Cinacalcete/uso terapêutico , Hiperparatireoidismo/tratamento farmacológico , Falência Renal Crônica/mortalidade , Estudos Observacionais como Assunto/estatística & dados numéricos , Diálise Renal/efeitos adversos , Adulto , Idoso , Viés , Calcimiméticos/administração & dosagem , Cálcio/sangue , Cinacalcete/administração & dosagem , Feminino , Humanos , Hiperparatireoidismo/etiologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Fósforo/sangue , Pontuação de PropensãoRESUMO
Chronic hepatitis B (CHB) infection affects approximately 90 million people in China, where there are profoundly unmet clinical and public health needs. This study evaluated patient demographics, disease progression, and treatment management using national administrative claims data. This retrospective, observational study used anonymized data from the China Health Insurance Research Association claims database (January 1-December 31, 2016); data that could not be validated, or from duplicate entries, were excluded. Patients were identified using the International Classification of Diseases, 10th Revision diagnostic code for CHB (B18.0 and B18.1), using keyword searches for "CHB or HBV" and free-text descriptions of CHB treatments including nucleos(t)ide analogues. Primary objectives included evaluation of: demographics and clinical characteristics of patients with CHB, overall and by presence or absence of cirrhosis and hospital tier; proportion of patients prescribed CHB treatment; and healthcare costs and utilization overall and by presence or absence of cirrhosis and hospital tier. Most identified patients with CHB were male, aged 25 to 65 years, resided in East China, and had employee health insurance. Cirrhosis was common (16.20%) and associated with male preponderance, older age, hepatitis C virus coinfection, and higher hospital care demands and costs. The most frequently visited hospitals were Tier III; patients visiting Tier III generally required more hospital care compared with those visiting Tier I/II hospitals. Only two-thirds of patients were prescribed antiviral therapy for CHB (most commonly nucleos(t)ide analogues). Results from this study highlight a substantial need to improve access to appropriate CHB treatment in China.
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Antivirais , Hepatite B Crônica , Humanos , Masculino , Feminino , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/complicações , Estudos Retrospectivos , Custos de Cuidados de Saúde , Cirrose Hepática/complicações , Vírus da Hepatite BRESUMO
Background and Aims: Functional cure, which requires sustained hepatitis B surface antigen (HBsAg) loss after treatment cessation, is currently the optimal treatment endpoint for chronic hepatitis B virus infection. We performed a systematic literature review (SLR) and meta-analyses to assess the association between HBsAg loss and long-term clinical outcomes. Methods: We performed a SLR of scientific literature published in Medline and Embase reporting the incidence of cirrhosis, hepatic decompensation (HD), hepatocellular carcinoma (HCC), liver-related mortality (LRM), and all-cause mortality (ACM) in relation to HBsAg status. Bayesian hierarchical commensurate prior meta-analyses synthesized evidence on the association between HBsAg loss and each outcome. Results: Thirty-eight studies, comprising 50,354 patients with 350,734 patient-years of follow-up, were included in the meta-analyses, reporting on cirrhosis (n = 12), HD (n = 12), HCC (n = 36), LRM (n = 12), and ACM (n = 16). Pooled incidence rate ratios (IRRs; vs HBsAg persistence) and respective credible intervals (Crls) were 0.28 (0.060-1.070) for cirrhosis, 0.13 (0.013-0.38) for HD, 0.27 (0.11-0.53) for HCC, 0.17 (0.028-0.61) for LRM, and 0.64 (0.24-1.17) for ACM. Single-predictor-adjusted IRRs remained consistent with those from the primary analyses for all outcomes except cirrhosis and LRM. Outcome incidence rates were modified by selected study, patient and infection characteristics, but trended in the same direction of reduced risk after loss. Conclusion: Overall, HBsAg loss was associated with a reduced risk of most clinically relevant outcomes. While the magnitude of the effect differed across subgroups, the direction of the association remained similar. Our results validate the need to develop new strategies to achieve HBsAg loss.
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INTRODUCTION: The prevalence of chronic hepatitis B virus (HBV) infection is high in many countries; however, robust, real-world epidemiological data are lacking. This study describes the prevalence, characteristics, treatment patterns, and long-term clinical outcomes of patients with chronic HBV infection in the US, Germany, and Taiwan. METHODS: This was a retrospective cohort analysis of three healthcare/insurance claims databases. Individuals were identified as patients with chronic HBV infection if their records contained HBV diagnostic codes from 1 January 2010 to 31 December 2012 (Germany and Taiwan) or 1 January 2013 (USA). Included patients were indexed on 1 January 2013. Patients' demographics, clinical characteristics, and healthcare utilisation were described. Treatment patterns and long-term clinical outcomes over follow-up (to 31 December 2016 or loss to follow-up) were estimated. RESULTS: The prevalence of chronic HBV infection was 0.10%, 0.17%, and 2.39% in the US, Germany, and Taiwan respectively. Prevalence was very low in children, increased rapidly in adulthood, and peaked in 50- < 65 year olds before declining in the elderly. More US (16.6%) and German (15.4%) patients were HIV ± HCV coinfected than in Taiwan (4.1%). Baseline clinical characteristics and healthcare utilisation were broadly similar between countries. In total, 19.2%, 11.1%, and 5.9% of non-coinfected adult patients received treatment at index in the US, Germany, and Taiwan, respectively; most frequently with nucleos(t)ide analogue monotherapy (94.4%, 97.2%, 99.8% of treated patients, respectively) and rarely with interferons (0.27%, 1.63%, and 0.06%, respectively). Untreated Taiwanese patients were more likely to remain untreated than elsewhere, and treated Taiwanese patients were less likely to persist with therapy. Generally, the cumulative incidence of long-term clinical outcomes was lowest in Germany. CONCLUSION: This study provides a contemporary, real-world, intercontinental snapshot of chronic HBV infection. Long-term sequelae occurred in all populations, and treatment levels were low, suggesting an unmet need for (or access to) effective treatments.
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Hepatite B Crônica , Adulto , Criança , Humanos , Idoso , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Estudos Retrospectivos , Antivirais/uso terapêutico , Estudos de Coortes , Resultado do Tratamento , Vírus da Hepatite BRESUMO
INTRODUCTION: Chronic hepatitis B virus (HBV) infection is associated with significant global morbidity and mortality. Low treatment rates are observed in patients living with HBV; the reasons for this are unclear. This study sought to describe patients' demographic, clinical and biochemical characteristics across three continents and their associated treatment need. METHODS: This retrospective cross-sectional post hoc analysis of real-world data used four large electronic databases from the United States, United Kingdom and China (specifically Hong Kong and Fuzhou). Patients were identified by first evidence of chronic HBV infection in a given year (their index date) and characterized. An algorithm was designed and applied, wherein patients were categorized as treated, untreated but indicated for treatment and untreated and not indicated for treatment based on treatment status and demographic, clinical, biochemical and virological characteristics (age; evidence of fibrosis/cirrhosis; alanine aminotransferase [ALT] levels, HCV/HIV coinfection and HBV virology markers). RESULTS: In total, 12,614 US patients, 503 UK patients, 34,135 patients from Hong Kong and 21,614 from Fuzhou were included. Adults (99.4%) and males (59.0%) predominated. Overall, 34.5% of patients were treated at index (range 15.9-49.6%), with nucleos(t)ide analogue monotherapy most commonly prescribed. The proportion of untreated-but-indicated patients ranged from 12.9% in Hong Kong to 18.2% in the UK; almost two-thirds of these patients (range 61.3-66.7%) had evidence of fibrosis/cirrhosis. A quarter (25.3%) of untreated-but-indicated patients were aged ≥ 65 years. CONCLUSION: This large real-world dataset demonstrates that chronic hepatitis B infection remains a global health concern; despite the availability of effective suppressive therapy, a considerable proportion of predominantly adult patients apparently indicated for treatment are currently untreated, including many patients with fibrosis/cirrhosis. Causes of disparity in treatment status warrant further investigation.
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Case-control studies are important in infectious disease epidemiology for rapidly identifying and controlling risks, but challenges, including the need for speed, can place practical restrictions on control selection and recruitment. The biased comparisons that result can hamper or, worse, mislead investigators. Following a 2009 outbreak of Shiga-like toxin-producing Escherichia coli O157 infection associated with a petting farm in southeast England, it was hypothesized that case behavior alone could be used to identify risks. Case-patients' exposures were randomized on a case-by-case basis, and the resulting permuted data were compared with the actual events preceding illness by conditional logistic regression analysis. There was good agreement between the risks identified by using our new method and the risks elicited in the original outbreak case-control studies. This was also the case in analysis of 2 further historical outbreaks. These initial findings suggest that the technique, which we have called the "case-chaos" technique, appeared to be useful in this setting. Analysis of simulated data supports this view. Circumventing the need for traditional control data has the potential to reduce outbreak investigation lead times, leading to earlier interventions and reduced morbidity and mortality. However, further validation is necessary, coupled with an awareness of limitations of the method.
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Estudos de Casos e Controles , Projetos de Pesquisa Epidemiológica , Medição de Risco/métodos , Viés , Simulação por Computador , Interpretação Estatística de Dados , Surtos de Doenças , Inglaterra/epidemiologia , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/etiologia , Escherichia coli O157 , Humanos , Modelos Logísticos , Razão de Chances , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Fatores de TempoRESUMO
The epidemiology of listeriosis in England and Wales changed during 2001-2008; more patients ≥60 years of age had bacteremia than in previous years. To investigate these changes, we calculated risk for listeriosis by concurrent condition for non-pregnancy-associated listeriosis cases reported to the national surveillance system in England during 1999-2009. Conditions occurring with L. monocytogenes infection were coded according to the International Classification of Diseases, 10th Revision, and compared with appropriate hospital episode statistics inpatient denominator data to calculate incidence rates/million consultations. Malignancies (especially of the blood), kidney disease, liver disease, diabetes, alcoholism, and age ≥60 years were associated with an increased risk for listeriosis. Physicians should consider a diagnosis of listeriosis when treating patients who have concurrent conditions. Providing cancer patients, who accounted for one third of cases, with food safety information might help limit additional cases.
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Listeria monocytogenes , Listeriose/complicações , Listeriose/epidemiologia , Neoplasias/complicações , Vigilância da População/métodos , Idoso , Bacteriemia/complicações , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Inglaterra/epidemiologia , Feminino , Humanos , Classificação Internacional de Doenças , Listeriose/microbiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , País de Gales/epidemiologiaRESUMO
A retrospective case-control study of listeriosis in patients in England aged over 60 years is described. The incidence of listeriosis in patients aged ≥60 years in England has doubled since 2001; hence, the investigation of risk factors for infection in this group is important to inform on prevention and control. Standardized epidemiological information has been sought on cases since 2005, but the value of the data accrued is limited without some perception of exposure prevalence in the population at risk of listeriosis. The exposures of listeriosis cases aged ≥60 years reported in England from 2005 to 2008 were compared to those of market research panel members representing the same population (i.e., residents of England aged ≥60 years) and time period. Exposures were grouped to facilitate comparison. Odds ratios and 95% confidence intervals were calculated. Cases were more likely than panel members to report the consumption of cooked meats (beef and ham/pork, but not poultry), cooked fish (specifically smoked salmon) and shellfish (prawns), dairy products (most noticeably milk but also certain cheeses), and mixed salads. They were less likely to report the consumption of other forms of seafood, dairy spread, other forms of dairy, sandwiches, and fresh vegetables. The diversity of high-risk food exposures reflects the ubiquity of the microorganism in the environment and/or the susceptibility of those at risk, and suggests that a wider variety of foods can give rise to listeriosis. Food safety advice on avoiding listeriosis should be adapted accordingly. While not inexpensive, the application of market research data to infectious disease epidemiology can add value to routine surveillance data.
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Listeriose/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Laticínios/microbiologia , Inglaterra/epidemiologia , Feminino , Doenças Transmitidas por Alimentos/etiologia , Doenças Transmitidas por Alimentos/microbiologia , Humanos , Lactuca/microbiologia , Listeria monocytogenes/isolamento & purificação , Masculino , Carne/microbiologia , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Alimentos Marinhos/microbiologia , Inquéritos e QuestionáriosRESUMO
Human listeriosis is a rare but serious foodborne disease, with high morbidity and mortality in vulnerable populations (e.g., pregnant women, the elderly, and the immunocompromised). The disease is predominantly caused by the consumption of contaminated ready-to-eat foods. Since 2001, an increase in the number of listeriosis cases has been observed in several European Union countries, including England and Wales, predominantly in the over-60s population. The cause of this selective increased incidence is unknown. The Hald Salmonella Bayesian source attribution model was adapted to determine the potential of this approach to quantify the contribution of different food sources to the burden of human listeriosis in England and Wales from 2004 to 2007. The most important food sources for the overall population were multicomponent foods (sandwiches and prepacked mixed salad vegetables) (23.1%), finfish (16.8%), and beef (15.3%). Attribution of major sources of infection was similar for the elderly population (>or=60 years old, multicomponent foods [22.0%], finfish [14.7%], and beef [13.6%]). For pregnancy-associated cases, beef (12.3%), milk and milk products (11.8%), and finfish (11.2%) were more important sources of infection. The adapted model also showed that the serotype 4b was associated with relatively more human infections than that of other serotypes; further, the subtype 4b amplified fragment-length polymorphism V was associated with more pregnancy-associated cases than other subtypes of 4b. This approach of quantifying the contribution of various food sources to human listeriosis provides a useful tool in food safety risk analysis, and underlines the need for further emphasis to be given to the reduction of Listeria monocytogenes in high-risk foods, such as multicomponent foods, which are consumed without any further treatment. The need for targeted dietary advice for the elderly population is also highlighted.
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Fast Foods/microbiologia , Microbiologia de Alimentos , Listeria monocytogenes , Listeriose/transmissão , Modelos Biológicos , Medição de Risco/métodos , Distribuição por Idade , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Teorema de Bayes , Dieta , Inglaterra/epidemiologia , Doenças Transmitidas por Alimentos/epidemiologia , Doenças Transmitidas por Alimentos/prevenção & controle , Prioridades em Saúde/tendências , Humanos , Listeria monocytogenes/classificação , Listeria monocytogenes/isolamento & purificação , Listeria monocytogenes/patogenicidade , Listeriose/epidemiologia , Listeriose/microbiologia , Listeriose/prevenção & controle , Vigilância da População , Fatores de Risco , Sorotipagem , País de Gales/epidemiologiaRESUMO
Characterization of immune responses is currently hampered by the lack of systems enabling quantitative and dynamic phenotypic characterization of individual cells and, in particular, analysis of secreted proteins such as cytokines and antibodies. We recently developed a simple and robust microfluidic platform, DropMap, to measure simultaneously the kinetics of secretion and other cellular characteristics, including endocytosis activity, viability and expression of cell-surface markers, from tens of thousands of single immune cells. Single cells are compartmentalized in 50-pL droplets and analyzed using fluorescence microscopy combined with an immunoassay based on fluorescence relocation to paramagnetic nanoparticles aligned to form beadlines in a magnetic field. The protocol typically takes 8-10 h after preparation of microfluidic chips and chambers, which can be done in advance. By contrast, enzyme-linked immunospot (ELISPOT), flow cytometry, time-of-flight mass cytometry (CyTOF), and single-cell sequencing enable only end-point measurements and do not enable direct, quantitative measurement of secreted proteins. We illustrate how this system can be used to profile downregulation of tumor necrosis factor-α (TNF-α) secretion by single monocytes in septic shock patients, to study immune responses by measuring rates of cytokine secretion from single T cells, and to measure affinity of antibodies secreted by single B cells.
Assuntos
Sistema Imunitário/citologia , Dispositivos Lab-On-A-Chip , Fenótipo , Análise de Célula Única/instrumentação , Animais , Linfócitos B/citologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Camundongos , Microscopia de FluorescênciaRESUMO
To explore hypotheses for age-related changes in the incidence of Campylobacter infections in England and Wales during 1990-2007, we analyzed electronic laboratory data. Disease incidence was reduced among children, and the greatest increase in risk was for those >/=60 years of age. Risk factors for campylobacteriosis in the elderly population should be identified.