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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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OBJECTIVE: Cholestatic pruritus in primary biliary cholangitis (PBC) reduces patients' health-related quality of life (HRQoL). Despite this, existing research suggests that pruritus is under-recorded in patients' health records. This study assessed the extent to which pruritus was recorded in medical records of patients with PBC as compared with patient-reported pruritus, and whether patients reporting mild itch were less likely to have pruritus recorded. We also evaluated clinico-demographic characteristics and HRQoL of patients with medical record-documented and patient-reported pruritus. DESIGN: This cross-sectional study used clinical information abstracted from medical records, together with patient-reported (PBC-40) data from patients with PBC in the USA enrolled in the PicnicHealth cohort. Medical record-documented pruritus was classified as 'recent' (at, or within 12 months prior to, enrolment) or 'ever' (at, or any point prior to, enrolment). Patient-reported pruritus (4-week recall) was assessed using the first PBC-40 questionnaire completed on/after enrolment; pruritus severity was classified by itch domain score (any severity: ≥1; clinically significant itch: ≥7). Patient clinico-demographic characteristics and PBC-40 domain scores were described in patients with medical record-documented and patient-reported pruritus; overlap between groups was evaluated. Descriptive statistics were reported. RESULTS: Pruritus of any severity was self-reported by 200/225 (88.9%) patients enrolled; however, only 88/225 (39.1%) had recent medical record-documented pruritus. Clinically significant pruritus was self-reported by 120/225 (53.3%) patients; of these, 64/120 (53.3%) had recent medical record-documented pruritus. Patients reporting clinically significant pruritus appeared to have higher mean scores across PBC-40 domains (indicating reduced HRQoL), versus patients with no/mild patient-reported pruritus or medical-record documented pruritus. CONCLUSION: Compared with patient-reported measures, pruritus in PBC is under-recorded in medical records and is associated with lower HRQoL. Research based only on medical records underestimates the true burden of pruritus, meaning physicians may be unaware of the extent and impact of pruritus, leading to potential undertreatment.
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Cirrose Hepática Biliar , Humanos , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/epidemiologia , Qualidade de Vida , Estudos Transversais , Prontuários Médicos , Prurido/epidemiologia , Prurido/complicações , Prurido/tratamento farmacológicoRESUMO
OBJECTIVES: Report the prevalence of eosinophilic granulomatosis with polyangiitis (EGPA) and describe oral corticosteroid (OCS) use and disease burden before and after mepolizumab approval in 2018 for EGPA in Japan. METHODS: Two retrospective studies (GSK IDs: 218083; 218084) used two databases: 1) the JMDC insurer database (Japanese health insurer claims) was used to report annual EGPA prevalence and OCS use in mepolizumab-treated patients; 2) Medical Data Vision database was used to report annual treatment use, OCS dose, relapses, and healthcare resource utilization (HCRU) in patients with EGPA. RESULTS: EGPA prevalence (95% confidence interval) increased from 4.2 (0.1, 23.4) in 2005 to 58.6 (53.2, 64.5) per 1,000,000 in 2020. Median OCS dose (mg/day) decreased from a range of 4.8-7.7 during 2010-2017 to 4.5-4.8 during 2018-2020 (lowest dose in 2020). The proportion of patients with prednisolone-equivalent daily OCS dose >10 mg decreased from 2017 (11.9%) to 2020 (10.3%), while the median dose halved. The proportion of patients with EGPA relapses (64.3% to 41.6%) and hospitalisation (27.8% to 23.6%) decreased from 2010 to 2020. CONCLUSIONS: EGPA prevalence increased between 2005 and 2020. With the introduction of mepolizumab for EGPA in 2018, real-world OCS use, relapses and HCRU decreased.
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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
INTRODUCTION: Data on the burden of hypereosinophilic syndrome (HES) are limited. This study investigated the incidence and prevalence of HES using real-world data from patients in the United Kingdom. METHODS: Primary care data from the Clinical Practice Research Datalink were analyzed. The patients of interest were identified using medical codes specific for HES. Annual incidence rates and prevalence were estimated for the years 2010-2018 (inclusive) using patients observed for a minimum period of one year. RESULTS: Between 2010 and 2018, 93 patients were identified with HES. During the study period the incidence of HES ranged from less than 0.04, 95% confidence interval (CI) (0.01-0.07) to 0.17, 95% CI (0.10-0.26) per 100,000 person-years and the prevalence ranged from 0.15, 95% CI (0.10-0.25) to 0.89, 95% CI (0.74-1.09) cases per 100,000 persons. Sensitivity analyses varying the minimum observation period required to identify HES patients gave similar results. CONCLUSION: These results provide estimates of the burden of HES in the United Kingdom and indicate that whilst HES is a very rare disease, there is evidence that is increasingly being recorded in UK primary care.
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Síndrome Hipereosinofílica , Bases de Dados Factuais , Humanos , Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/epidemiologia , Incidência , Prevalência , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Population-based and clinical case reports of hyperhidrosis (HH) provide prevalence estimates that vary widely across reported studies because of differences in case ascertainment. OBJECTIVE: In this study, we specify diagnostic, symptom, and prescription codes for HH to estimate incidence and prevalence for the United Kingdom and the United States. METHODS: Data from UK and US health care databases were analyzed to ascertain HH cases and estimate incidence and prevalence from health care records during calendar years 2011 through 2013. RESULTS: On the basis of 2013 data for the United States and United Kingdom, between 1.0% and 1.6% of these populations have health care records indicating diagnosis or treatment of HH. Women accounted for approximately 60% of incident and prevalent cases in both databases. LIMITATIONS: Because the case ascertainment methods rely on available data for those seeking health care, we may have underestimated the number of HH cases in both countries. CONCLUSIONS: The findings represent a plausible estimate for incidence and prevalence of HH among persons seeking medical care for excessive sweating. Improved practices for identifying HH in clinical settings may increase the sensitivity and specificity of future studies and improve characterization and quantification of the population burden of this significant disease.
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Hiperidrose/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Prevalência , Reino Unido/epidemiologia , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: The burden of respiratory syncytial virus (RSV) illness is not well characterised in primary care. We estimated the burden of disease attributable to RSV in children in the UK between 1995 and 2009. DESIGN: Time-series regression modelling. SETTING: A multiple linear regression model based on weekly viral surveillance (RSV and influenza, Public Health England), and controlled for non-specific seasonal drivers of disease, estimated the proportion of general practitioner (GP) episodes of care (counted as first visit in a series within 28â days; Clinical Practice Research Datalink, CPRD), hospitalisations (Hospital Episode Statistics, HES) and deaths (Office of National Statistics, ONS) attributable to RSV each season. PARTICIPANTS: Children 0-17â years registered with a GP in CPRD, or with a respiratory disease outcome in the HES or ONS databases. PRIMARY OUTCOME MEASURES: RSV-attributable burden of GP episodes, hospitalisations and deaths due to respiratory disease by age. RSV-attributable burden associated with selected antibiotic prescriptions. RESULTS: RSV-attributable respiratory disease in the UK resulted in an estimated 450â 158 GP episodes, 29â 160 hospitalisations and 83 deaths per average season in children and adolescents, with the highest proportions in children <6â months of age (14â 441/100â 000 population, 4184/100â 000 and 6/100â 000, respectively). In an average season, there were an estimated 125â 478 GP episodes for otitis media and 416â 133 prescriptions for antibiotics attributable to RSV. More GP episodes, hospitalisations and deaths from respiratory disease were attributable to RSV than to influenza in children under 5â years. CONCLUSIONS: The burden of RSV in children in the UK exceeds that of influenza. RSV in children and adolescents contributes substantially to GP office visits for a diverse range of illnesses, and was associated with an average 416â 133 prescribed antibiotic courses per season. Effective antiviral treatments and preventive vaccines are urgently needed for the management of RSV infection in children. TRIAL REGISTRATION NUMBER: NCT01706302.
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Prescrições de Medicamentos/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Otite Média/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Estações do Ano , Adolescente , Distribuição por Idade , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Bases de Dados Factuais , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Modelos Lineares , Masculino , Atenção Primária à Saúde , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Reino Unido/epidemiologiaRESUMO
Recent studies on the epidemiology of the inner-ear disorder Ménière's disease (MD) use disparate methods for sample selection, case identification and length of observation. Prevalence estimates vary geographically from 17 to 513 cases per 100,000 people. We explored the impact of case detection strategies and observation periods in estimating the prevalence of MD in the USA, using data from a large insurance claims database. Using case detection strategies of ≥1, ≥2 and ≥3 ICD-9 claim codes for MD within a 1-year period, the 2012 prevalence estimates were 66, 27 and 14 cases per 100,000 people, respectively. For ≥1, ≥2 and ≥3 insurance claims within a 3-year observation period, the prevalence estimates were 200, 104 and 66 cases per 100,000 people, respectively. Estimates based on a single claim are likely to overestimate prevalence; this conclusion is aligned with the American Academy of Otolaryngology-Head and Neck Foundation criteria requiring ≥2 definitive episodes for a definite diagnosis, and it has implications for future epidemiologic research. We believe estimates for ≥2 claims may be a more conservative estimate of the prevalence of MD, and multiyear estimates may be needed to allow for adequate follow-up time.
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Doença de Meniere/epidemiologia , Adolescente , Adulto , Idoso , Criança , Bases de Dados Factuais , Feminino , Humanos , Classificação Internacional de Doenças , Masculino , Informática Médica , Pessoa de Meia-Idade , Prevalência , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Annual seasonal influenza vaccination is recommended for transplant recipients. No formal pharmacoepidemiology study has been published on the association between solid organ transplant (SOT) rejection and vaccination with seasonal trivalent inactivated influenza vaccines (TIIVs). METHODS: The risk of SOT (liver, kidney, lung, heart or pancreas) rejection after TIIV vaccination was assessed using a self-controlled case-series method (NCT01715792). SOT recipients in England with transplant rejection were selected from the Clinical Practice Research Datalink and linked Hospital Episode Statistics inpatient data. The study period (September 2006 to August 2009) encompassed three consecutive influenza seasons. We calculated the relative incidence (RI) of SOT rejection between the 30- and 60-day post-vaccination risk periods and the control periods (any follow-up period excluding risk periods), using a Poisson regression model. RESULTS: In seasons 2006/07, 2007/08, 2008/09 and pooled seasons, 132, 136, 168 and 375 subjects, respectively, experienced at least one transplant rejection; approximately half (45%-51%) of these subjects had received a TIIV. For season 2006/07, the RI of rejection of any organ, adjusted for time since transplantation, was 0.74 (95% CI: 0.24-2.28) and 0.58 (95% CI: 0.24-1.38) during the 30-day and 60-day risk periods, respectively. Corresponding RIs for season 2007/08 were 1.21 (95% CI: 0.55-2.64) and 1.31 (95% CI: 0.69-2.48); for season 2008/09, 0.99 (95% CI: 0.43-2.28) and 0.64 (95% CI: 0.31-1.33); and for pooled seasons 1.01 (95% CI: 0.58-1.76) and 0.88 (95% CI: 0.56-1.38). The results of a separate analysis of kidney rejections and analyses that took into account additional potential confounders were consistent with those of the main analyses, with 95% CIs including 1 and upper limits below 3. CONCLUSION: This study provides reassuring evidence of the safety profile of TIIVs in SOT recipients, thus supporting current recommendations to vaccinate this risk group annually.
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Rejeição de Enxerto/epidemiologia , Vacinas contra Influenza/administração & dosagem , Transplantados , Vacinação/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Inglaterra , Feminino , Humanos , Lactente , Vacinas contra Influenza/efeitos adversos , Influenza Humana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Vigilância de Produtos Comercializados , Estudos Retrospectivos , Medição de Risco , Adulto JovemRESUMO
PURPOSE: Results from observational studies on the same exposure-outcome association may be inconsistent because of variations in methodological factors, clinical factors or health care systems. We evaluated the consistency of results assessing the association between antidepressant use and the risk of hip/femur fractures in three European primary care databases using two different study designs. METHODS: Cohort and nested case control studies were conducted in three European primary care databases (Spanish BIFAP, Dutch Mondriaan and UK THIN) to assess the association between use of antidepressants and hip/femur fracture. A common protocol and statistical analysis plan was applied to harmonize study design and conduct between data sources. RESULTS: Current use of antidepressants was consistently associated with a 1.5 to 2.5-fold increased risk of hip/femur fractures in all data sources with both designs, with estimates for SSRIs generally higher than those for TCAs. In general, risk estimates in Mondriaan, the smallest data source, were higher compared to the other data sources. This difference may be partially explained by an interaction between SSRI and age in Mondriaan. Adjustment for GP-recorded lifestyle factors and matching on general practice had negligible impact on adjusted relative risk estimates. CONCLUSION: We found a consistent increased risk of hip/femur fracture with current use of antidepressants across different databases and different designs. Applying similar pharmacoepidemiological study methods resulted in similar risks for TCA use and some variation for SSRI use. Some of these differences may express real (or natural) variance in the exposure-outcome co-occurrences.
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Antidepressivos/efeitos adversos , Fraturas do Quadril/etiologia , Farmacoepidemiologia/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Fêmur/lesões , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Farmacoepidemiologia/estatística & dados numéricos , Fatores de RiscoRESUMO
OBJECTIVE: To assess the risk of solid organ transplant (SOT) rejection after vaccination with the adjuvanted (AS03) A/H1N1 2009 pandemic influenza vaccine Pandemrix. DESIGN: Self-controlled case series (SCCS) in the UK Clinical Practice Research Datalink (CPRD) and its linked component of the Hospital Episodes Statistics (HES) inpatient database. Analyses were conducted using the SCCS method for censored, perturbed or curtailed post-event exposure. PARTICIPANTS: Of the 184 transplant recipients having experienced at least one SOT rejection (liver, kidney, lung, heart or pancreas) during the study period from 1 October 2009 to 31 October 2010, 91 participants were included in the main analysis, of which 71 had been exposed to Pandemrix. MAIN OUTCOME MEASURES: Occurrence of SOT rejection during risk (30 and 60 days after any Pandemrix dose) and control periods. Covariates in the CPRD included time since transplantation, seasonal influenza vaccination, bacterial and viral infections, previous SOT rejections and malignancies. RESULTS: The relative incidence (RI) of rejection of any one of the five transplanted organs, adjusted for time since transplantation, was 1.05 (95% CI 0.52 to 2.14) and 0.80 (95% CI 0.42 to 1.50) within 30 and 60 days after vaccination, respectively. Similar estimates were observed for rejection of a kidney only, the most commonly transplanted organ (RI within 30 days after vaccination: 0.85 (95% CI 0.38 to 1.90)). Across various models and sensitivity analyses, RI estimates remained stable and within a consistent range around 1.0. CONCLUSIONS: These results suggest a reassuring safety profile for Pandemrix with regard to the risk of rejection in SOT recipients in England and contribute to inform the benefit-risk of AS03-adjuvanted pandemic influenza vaccines in transplanted patients in the event of future pandemics. TRIAL REGISTRATION NUMBER: NCT01715792.
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Rejeição de Enxerto , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Medição de Risco , Vacinação , Humanos , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Reino Unido , Vacinação/efeitos adversosRESUMO
BACKGROUND: The case-crossover (CXO) and self-controlled case series (SCCS) designs are increasingly used in pharmacoepidemiology. In both, relative risk estimates are obtained within persons, implicitly controlling for time-fixed confounding variables. OBJECTIVES: To examine the consistency of relative risk estimates of hip/femur fractures (HFF) associated with the use of benzodiazepines (BZD) across case-only designs in two databases (DBs), when a common protocol was applied. METHODS: CXO and SCCS studies were conducted in BIFAP (Spain) and CPRD (UK). Exposure to BZD was divided into non-use, current, recent and past use. For CXO, odds ratios (OR; 95%CI) of current use versus non-use/past were estimated using conditional logistic regression adjusted for co-medications (AOR). For the SCCS, conditional Poisson regression was used to estimate incidence rate ratios (IRR; 95%CI) of current use versus non/past-use, adjusted for age. To investigate possible event-exposure dependence the relative risk in the 30 days prior to first BZD exposure was also evaluated. RESULTS: In the CXO current use of BZD was associated with an increased risk of HFF in both DBs, AORBIFAP = 1.47 (1.29-1.67) and AORCPRD = 1.55 (1.41-1.70). In the SCCS, IRRs for current exposure was 0.79 (0.72-0.86) in BIFAP and 1.21 (1.13-1.30) in CPRD. However, when we considered separately the 30-day pre-exposure period, the IRR for current period was 1.43 (1.31-1.57) in BIFAP and 1.37 (1.27-1.47) in CPRD. CONCLUSIONS: CXO designs yielded consistent results across DBs, while initial SCCS analyses did not. Accounting for event-exposure dependence, estimates derived from SCCS were more consistent across DBs and designs.
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Benzodiazepinas/efeitos adversos , Bases de Dados Factuais/normas , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Projetos de PesquisaRESUMO
BACKGROUND: Results from observational studies may be inconsistent because of variations in methodological and clinical factors that may be intrinsically related to the database (DB) where the study is performed. OBJECTIVES: The objectives of this paper were to evaluate the impact of applying a common study protocol to study benzodiazepines (BZDs) (anxiolytics, hypnotics, and related drugs) and the risk of hip/femur fracture (HFF) across three European primary care DBs and to investigate any resulting discrepancies. METHODS: To measure the risk of HFF among adult users of BZDs during 2001-2009, three cohort and nested case control (NCC) studies were performed in Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) (Spain), Clinical Practice Research Datalink (CPRD) (UK), and Mondriaan (The Netherlands). Four different models (A-D) with increasing levels of adjustment were analyzed. The risk according to duration and type of BZD was also explored. Adjusted hazard ratios (cohort), odds ratios (NCC), and their 95% confidence intervals were estimated. RESULTS: Adjusted hazard ratios (Model C) were 1.34 (1.23-1.47) in BIFAP, 1.66 (1.54-1.78) in CPRD, and 2.22 (1.55-3.29) in Mondriaan in cohort studies. Adjusted odds ratios (Model C) were 1.28 (1.16-1.42) in BIFAP, 1.60 (1.49-1.72) in CPRD, and 1.48 (0.89-2.48) in Mondriaan in NCC studies. A short-term effect was suggested in Mondriaan, but not in CPRD or BIFAP. All DBs showed an increased risk with the concomitant use of anxiolytic and hypnotic drugs. CONCLUSIONS: Applying similar study methods to different populations and DBs showed an increased risk of HFF in BZDs users but differed in the magnitude of the risk, which may be because of inherent differences between DBs.
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Benzodiazepinas/efeitos adversos , Bases de Dados Factuais/normas , Fraturas do Quadril/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiolíticos/efeitos adversos , Estudos de Casos e Controles , Estudos de Coortes , União Europeia , Feminino , Humanos , Hipnóticos e Sedativos/efeitos adversos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Our main aim was to assess the level of persistence and adherence to therapy with glucagon-like peptide-1 (GLP-1) receptor agonists in type 2 diabetes mellitus (T2DM) patients in the United Kingdom (UK) and Germany, also by comparing once- (OD) with twice-a-day (BID) therapy. METHODS: We used two large retrospective datasets: a German claims dataset and the UK General Practitioner (GP)-based Clinical Practice Research Datalink (CPRD) dataset (2010-2012). All continuously insured T2DM patients with at least one outpatient/inpatient T2DM diagnosis were observed starting with the first prescription of a GLP-1 receptor agonist. Non-persistence (NP) was defined as treatment gap >90 days. Non-adherence (NA) was defined as medication possession ratio <80%, calculated during a period in which a patient continued therapy (no treatment gap >90 days) only. RESULTS: In the UK sample, 1905 T2DM patients started a treatment with GLP-1 receptor agonists (mean age: 55.5 years, 47.2% female). In the German sample, 1627 T2DM patients started a treatment with GLP-1 receptor agonists (mean age: 56.6 years, 51.4% female). Percentage of NP patients after 12 months was 29.5% in the UK and 36.4% in the German sample. In both countries, a BID treatment was associated with a higher probability to discontinue a treatment with GLP-1 receptor agonists earlier than an OD treatment (hazard ratio [HR] = 1.431 in UK and HR = 1.314 in Germany). The percentages of patients considered NA were 20.2%/20.0%/20.5% (all/OD/BID) for the UK sample, and 19.9%/19.2%/21.8% (all/OD/BID) for the German sample. CONCLUSION: NP and NA to treatment with GLP-1 receptor agonists in both UK and Germany appear to be similar. Persistence to OD treatment is higher than to BID treatment in both the UK and Germany.
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BACKGROUND: Growing evidence suggests respiratory syncytial virus (RSV) is an important cause of respiratory disease in adults. However, the adult burden remains largely uncharacterized as most RSV studies focus on children, and population-based studies with laboratory-confirmation of infection are difficult to implement. Indirect modelling methods, long used for influenza, can further our understanding of RSV burden by circumventing some limitations of traditional surveillance studies that rely on direct linkage of individual-level exposure and outcome data. METHODS: Multiple linear time-series regression was used to estimate RSV burden in the United Kingdom (UK) between 1995 and 2009 among the total population and adults in terms of general practice (GP) episodes (counted as first consultation ≥28 days following any previous consultation for same diagnosis/diagnostic group), hospitalisations, and deaths for respiratory disease, using data from Public Health England weekly influenza/RSV surveillance, Clinical Practice Research Datalink, Hospital Episode Statistics, and Office of National Statistics. The main outcome considered all ICD-listed respiratory diseases and, for GP episodes, related symptoms. Estimates were adjusted for non-specific seasonal drivers of disease using secular cyclical terms and stratified by age and risk group (according to chronic conditions indicating severe influenza risk as per UK recommendations for influenza vaccination). Trial registration NCT01706302 . Registered 11 October 2012. RESULTS: Among adults aged 18+ years an estimated 487,247 GP episodes, 17,799 hospitalisations, and 8,482 deaths were attributable to RSV per average season. Of these, 175,070 GP episodes (36 %), 14,039 hospitalisations (79 %) and 7,915 deaths (93 %) were in persons aged 65+ years. High- versus low-risk elderly were two-fold more likely to have a RSV-related GP episode or death and four-fold more likely be hospitalised for RSV. In most seasons since 2001, more GP episodes, hospitalisations and deaths were attributable to RSV in adults than to influenza. CONCLUSION: RSV is associated with a substantial disease burden in adults comparable to influenza, with most of the hospitalisation and mortality burden in the elderly. Treatment options and measures to prevent RSV could have a major impact on the burden of RSV respiratory disease in adults, especially the elderly.
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Infecções por Vírus Respiratório Sincicial/epidemiologia , Adolescente , Adulto , Idoso , Doença Crônica , Bases de Dados Factuais , Feminino , Hospitalização , Humanos , Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Infecções por Vírus Respiratório Sincicial/mortalidade , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/isolamento & purificação , Estações do Ano , Reino Unido/epidemiologia , Adulto JovemRESUMO
PURPOSE: Considerations for using administrative claims data in research have not been well-described. To increase awareness of how enrollment factors and insurance benefit use may contribute to prevalence estimates, we evaluated how differences in operational definitions of the cohort impact observed estimates. METHODS: We conducted a cross-sectional study estimating the prevalence of five gastrointestinal conditions using MarketScan claims data for 73.1 million enrollees. We extracted data obtained from 2009 to 2012 to identify cohorts meeting various enrollment, prescription drug benefit, or health care utilization characteristics. Next, we identified patients meeting the case definition for each of the diseases of interest. We compared the estimates obtained to evaluate the influence of enrollment period, drug benefit, and insurance usage. RESULTS: As the criteria for inclusion in the cohort became increasingly restrictive the estimated prevalence increased, as much as 45% to 77% depending on the disease condition and the definition for inclusion. Requiring use of the insurance benefit and a longer period of enrollment had the greatest influence on the estimates observed. CONCLUSIONS: Individuals meeting case definition were more likely to meet the more stringent definition for inclusion in the study cohort. This may be considered a form of selection bias, where overly restrictive inclusion criteria definitions may result in selection of a source population that may no longer represent the population from which cases arose.
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Viés , Gastroenteropatias/epidemiologia , Revisão da Utilização de Seguros/estatística & dados numéricos , Seguro Saúde/estatística & dados numéricos , Seleção de Pacientes , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Serviços de Saúde/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Seguro de Serviços Farmacêuticos/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prevalência , Estados Unidos/epidemiologia , Adulto JovemRESUMO
INTRODUCTION: Retapamulin, a topical pleuromutilin that selectively inhibits bacterial protein synthesis, is approved for treatment of impetigo and secondarily infected traumatic lesions in adults and in children older than 9 months of age. OBJECTIVE: A 5-year study was conducted to monitor prescription use in children younger than 9 months of age. METHODS: Annual prescription events were monitored in the UK Clinical Practice Research Datalink (CPRD) and the Clinformatics™ DataMart Multiplan (IMPACT), a product of OptumInsight Life Sciences, Inc. (Eden Prairie, MN, USA), from the USA. RESULTS: In the CPRD, of 148 prescriptions, three (2 %) were identified in children aged less than 9 months between years 2008 and 2011. In IMPACT, of 59,210 claims for retapamulin in children, 1,951 (3.3 %) were categorized as definitive, or uncertain for, less than 9 months of age between 2007 and 2011. CONCLUSION: Retapamulin prescription events in children aged less than 9 months were relatively low compared with other recent estimations of off-label pediatric medicines. Our report provides a framework for future investigations and discussions that may facilitate off-label reporting schemes and promote pediatric drug safety.
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Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Impetigo/tratamento farmacológico , Uso Off-Label , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Diterpenos , Humanos , Lactente , Pessoa de Meia-IdadeRESUMO
PURPOSE: High doses of gabapentin were associated with pancreatic acinar cell tumors in male Wistar rats, but there is little published epidemiological data regarding gabapentin and carcinogenicity. We explored the association between gabapentin and cancer in a US medical care program and followed up nominally significant associations in a UK primary care database. METHODS: In the US Kaiser Permanente Northern California (KPNC) health system, we performed nested case-control analyses of gabapentin and 55 cancer sites and all cancers combined using conditional logistic regression. Up to 10 controls were matched to each case on year of birth, sex, and year of cohort entry. No other covariates were included in models. Only dispensings for gabapentin 2 years or more before index date were considered. Nominally significant associations with an OR > 1.00 and p < 0.05 for three or more dispensings versus no dispensings were followed up by similar nested case-control analyses in the UK General Practice Research Database (GPRD), adjusting for potential indications for gabapentin and risk factors for the specific cancers. RESULTS: The following analyses had OR > 1.00 and p < 0.05 for three or more dispensings of gabapentin versus no dispensing (2-year lag) in KPNC and were also examined in the GPRD: all cancers, breast, lung and bronchus, urinary bladder, kidney/renal pelvis, stomach, anus/anal canal/anorectum, penis, and other nervous system. These cancers were not statistically significantly associated with gabapentin in the GPRD case-control studies (2-year lag). The GPRD and KPNC studies did not identify a statistically significant increased risk of pancreatic cancer with more than two prescriptions of gabapentin in the 2-year lagged analyses. CONCLUSIONS: The epidemiological data in a US cohort with up to 12 years of follow-up and a UK cohort with up to 15 years of follow-up do not support a carcinogenic effect of gabapentin use. However, the confidence intervals for some analyses were wide, and an important effect cannot be confidently excluded.
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Aminas/efeitos adversos , Anticonvulsivantes/efeitos adversos , Ácidos Cicloexanocarboxílicos/efeitos adversos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Neoplasias/etiologia , Ácido gama-Aminobutírico/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , California/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Seguimentos , Gabapentina , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/patologia , Risco , Reino Unido/epidemiologia , Estados Unidos/epidemiologiaRESUMO
INTRODUCTION: Data regarding the prevalence of immune thrombocytopenia (ITP) is limited, and is derived from North American population-based analyses. Therefore, the authors conducted the first study outside the United States (US) using the United Kingdom (UK) General Practice Research Database (GPRD) to estimate the adult prevalence of ITP in the UK. METHODS: This study estimated the diagnosed prevalence of ITP in the adult population in UK using the GPRD from January 1, 1992 to December 31, 2009. RESULTS: The unadjusted, overall 18-year period prevalence was 50.29/100,000 (95% CI: 48.51, 52.06). The age- and gender-adjusted, overall 18-year period prevalence was 50.00/100,000 (95% CI: 49.20, 50.90). ITP prevalence was lower in adults aged 18-49 years of age (30.09/100,000, 95% CI: 28.27, 31.90) than in older adults aged 50-64 years of age (58.22/100,000, 95% CI: 53.88, 62.57) or ≥65 years of age (93.80/100,000, 95% CI: 88.76, 98.85). Prevalence was higher among females (59.32/100,000, 95% CI: 56.63, 62.01) than in males (40.66/100,000, 95% CI: 38.36, 42.96). Prevalence in the GPRD increased over time (1992 [16.33/100,000, 95% CI: 13.70, 19.00], 2000 [36.93/100,000, 95% CI: 34.50, 39.30], and 2009 [58.49/100,000, 95% CI: 55.80, 61.20]). CONCLUSION: This new analysis of general practice in the UK provides robust prevalence estimates of diagnosed ITP among adults in Europe. ITP prevalence is higher in women and increases with age and over time.
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Púrpura Trombocitopênica Idiopática/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Púrpura Trombocitopênica Idiopática/diagnóstico , Estudos Retrospectivos , Distribuição por Sexo , Fatores de Tempo , Reino Unido/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The risk of thromboembolic events in adults with primary immune thrombocytopenia has been little investigated despite findings of increased susceptibility in other thrombocytopenic autoimmune conditions. The objective of this study was to evaluate the risk of thromboembolic events among adult patients with and without primary immune thrombocytopenia in the UK General Practice Research Database. DESIGN AND METHODS: Using the General Practice Research Database, 1,070 adults (>or=18 years) with coded records for primary immune thrombocytopenia first referenced between January 1(st) 1992 and November 30(th) 2007, and having at least one year pre-diagnosis and three months post-diagnosis medical history were matched (1:4 ratio) with 4,280 primary immune thrombocytopenia disease free patients by age, gender, primary care practice, and pre-diagnosis observation time. The baseline prevalence and incidence rate of thromboembolic events were quantified, with comparative risk modelled by Cox's proportional hazards regression. RESULTS: Over a median 47.6 months of follow-up (range: 3.0-192.5 months), adjusted hazard ratios of 1.58 (95% CI, 1.01-2.48), 1.37 (95% CI, 0.94-2.00), and 1.41 (95% CI, 1.04-1.91) were found for venous, arterial, and combined (arterial and venous) thromboembolic events, respectively, when comparing the primary immune thrombocytopenia cohort with the primary immune thrombocytopenia disease free cohort. Further event categorization revealed an elevated incidence rate for each occurring venous thromboembolic subtype among the adult patients with primary immune thrombocytopenia. CONCLUSIONS: Patients with primary immune thrombocytopenia are at increased risk for venous thromboembolic events compared with patients without primary immune thrombocytopenia.