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1.
Birth Defects Res A Clin Mol Teratol ; 79(4): 309-16, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17286297

ABSTRACT

BACKGROUND: As part of an effort to validate the General Practice Research Database (GPRD) for future studies of medication use in pregnancy, this study examined whether the rates of all, and specific types of, congenital heart defects obtained from the GPRD are similar to those obtained from UK national systems. METHODS: The prevalence rates of heart defects for 2001-2003 were determined from the GPRD and compared with both the National Congenital Anomaly System (NCAS) and the European Concerted Action of Congenital Anomalies and Twins (EUROCAT). Rate ratios (RRs) and 95% CIs were calculated comparing the prevalence of all congenital heart defects as well as specific types of heart defects in the three data sources. In addition, the effect of the child's age on the frequency of heart defects in the GPRD was determined. RESULTS: The prevalence of heart defects in the GPRD was more than twice as high as in the NCAS and slightly higher than in the EUROCAT. All differences were statistically significant. The prevalence of specific heart defects varied across the GPRD, NCAS, and EUROCAT. The measured prevalence of congenital heart defects in the GPRD was higher if calculated including children up to age 6. CONCLUSIONS: The comparisons of the GPRD prevalence rates to national prevalence estimates demonstrate that the GPRD can serve as a more complete source of background prevalence for the most commonly occurring congenital heart defects, which is essential to properly assess possible associations between maternal exposures and congenital heart defects.


Subject(s)
Databases, Factual/standards , Family Practice , Heart Defects, Congenital/epidemiology , Registries/standards , Child , Child, Preschool , Europe/epidemiology , Humans , Infant , Infant, Newborn , Prevalence , United Kingdom/epidemiology
2.
Pediatr Diabetes ; 7(3): 159-64, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16787523

ABSTRACT

BACKGROUND: Tight glycemic control delays the long-term complications of type 1 diabetes mellitus (T1DM) but increases the risk for hypoglycemia. The continuous glucose-monitoring system (CGMS) provides blood glucose (BG) readings every 5 min, and its accuracy and reliability has been established in adults. However, there are limited data on its efficacy and safety in children. The purpose of this study was to determine if CGMS use improves metabolic control in children with T1DM. METHODS: Twenty-seven children (12 male) with T1DM participated in this single-blind, randomized, controlled trial. Participants (age: 11.4 +/- 3.7 (mean +/- SD) yr, range: 7-17 yr) were randomized to an intervention group (n = 18) or a control group (n = 9). Both groups wore the CGMS for 72-h periods at 0, 2, and 4 months. Adjustments in therapy for the intervention group were based on both CGMS and self-monitoring of BG (SMBG) data, while only SMBG data were used for the control group. Hemoglobin A1c (HbA1c) was determined at 0, 2, 4, and 6 months. The change in HbA1c from 0 to 6 months (HbA1c(Delta1-4)) and mean daily area under the CGMS curve for glucose <70 mg/dL area under the curve (AUC(<70)) were compared between groups. RESULTS: At study entry, HbA1c levels were similar in the intervention and control groups (8.4 +/- 0.98 and 8.8 +/- 0.86%, respectively; p = 0.12) but were significantly lower in the intervention group compared with the control group at study completion (7.8 +/- 0.88 and 8.6 +/- 0.95%, respectively; p = 0.02). The decrease in HbA1c of 0.61 +/- 0.68% in the intervention group was statistically significant (p = 0.03), whereas the decrease in HbA1c of 0.28 +/- 0.78% in the control group was not. Nonetheless, the differences in HbA1c(Delta1-4) between groups did not reach statistical significance (p = 0.13). There was no statistically significant difference in AUC(<70) between study groups (p = 0.18). CONCLUSION: CGMS use may improve metabolic control in children with T1DM without increasing the risk for hypoglycemia.


Subject(s)
Blood Glucose Self-Monitoring/methods , Blood Glucose/analysis , Diabetes Mellitus, Type 1/blood , Glycated Hemoglobin/analysis , Hypoglycemia/prevention & control , Adolescent , Area Under Curve , Blood Glucose Self-Monitoring/instrumentation , Child , Diabetes Mellitus, Type 1/diagnosis , Female , Humans , Male , Single-Blind Method
3.
Am J Epidemiol ; 163(9): 838-48, 2006 May 01.
Article in English | MEDLINE | ID: mdl-16554352

ABSTRACT

This study investigated the relation between weekly levels of influenza activity and the risk of acute influenza-like illness episodes among 8,323 healthy pregnant and postpartum women enrolled in a Puget Sound region, Washington, health maintenance organization, Group Health Cooperative, between June 1991 and December 1997. The authors classified weeks between October and May for isolate activity level based on surveillance data for influenza, respiratory syncytial virus, parainfluenza, and adenovirus infection. Influenza-like illness episodes were identified from medical encounters assigned a diagnostic code consistent with a symptomatic influenza infection. The authors compared the occurrence of influenza-like illness episodes within each pregnancy stage for periods with varying levels of influenza isolate detection in the community. Repeated-measures logistic regression methods accounted for time-dependent factors. The adjusted strength of association between influenza exposure and influenza-like illness episodes increased as the pregnancy stage progressed (first trimester odds ratio = 1.12, 95% confidence interval: 0.79, 1.59; second trimester odds ratio = 1.30, 95% confidence interval: 0.97, 1.73; third trimester odds ratio = 1.84, 95% confidence interval: 1.31, 2.59; postpartum period odds ratio = 2.28, 95% confidence interval: 1.42, 3.68). Pregnancy stage modified the association between influenza activity and influenza-like illness episodes. Findings estimate that 20-43 pregnant/postpartum women would need to be vaccinated with an 80% effective vaccine to prevent one influenza-like illness episode.


Subject(s)
Influenza, Human/epidemiology , Postpartum Period , Pregnancy Complications, Infectious/epidemiology , Acute Disease , Female , Humans , Incidence , Influenza, Human/prevention & control , Odds Ratio , Pregnancy , Pregnancy Complications, Infectious/prevention & control , Prognosis , Retrospective Studies , Risk Factors , Vaccination , Washington/epidemiology
4.
Pharmacoepidemiol Drug Saf ; 15(2): 81-92, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16287211

ABSTRACT

For many adverse effects of drugs, the instantaneous risk of an incident event per day of therapy (i.e., the hazard function) varies by duration of therapy and by prior exposure. In cohort studies of adverse drug effects time-varying hazard functions are easily modeled using standard statistical software packages. Tests of the hypothesis of a constant proportional hazard function ratio are also available. In case control studies, the need to consider time-varying hazard functions seems to be somewhat less well-recognized than in cohort studies. When the hazard function ratio for an adverse drug event is not constant over time, an overall single odds ratio (OR) estimated in a case control study not accounting for the time variation in the hazard function is a weighted average of duration-specific ORs with weights reflecting the distribution of exposure time in the study population. The resulting estimate depends not only on the drug but also on the exposure time distribution in the study population. This can lead to misleading conclusions when comparing the risks of two drugs within the same population and when comparing risks of the same drug in different populations. Analytic approaches for addressing time-varying hazard functions in case-control studies have been published but seem to be less used than in cohort studies. This article discusses adverse drug effects with time-varying hazard functions and methods for addressing these in case-control studies during study design, data collection, and analysis.


Subject(s)
Case-Control Studies , Drug-Related Side Effects and Adverse Reactions , Epidemiologic Research Design , Pharmacoepidemiology/methods , Proportional Hazards Models , Time Factors , Data Interpretation, Statistical , Humans , Odds Ratio
5.
Urology ; 66(5): 1038-42, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16286120

ABSTRACT

OBJECTIVES: To estimate the declining benefits of screening for prostate cancer as patient age at screening increases. The benefits of prostate cancer screening decline with age because of the long natural history of prostate cancer and competing causes of death among older men. METHODS: We used a previously described Monte Carlo simulation based on a Markov model of prostate cancer detection in men aged 40 to 90 years and simulated prostate cancer screening in 1000 populations of 1,000,000 men each. The age at the final prostate-specific antigen test in the model was varied to simulate the discontinuation of screening from age 50 to 80 years. The model outputs were the number of men treated, the number of prostate cancer deaths prevented by treatment, and person-years of life saved. RESULTS: The relationship between treatments required to prevent a death was not constant but widened with age. Compared with screening to age 65 years, screening to age 75 and 80 years required twice and three times, respectively, the number of treatments per person-year of life saved. CONCLUSIONS: Our results have helped to quantify the declining treatment benefit as the patient age at screening and treatment for prostate cancer increases. We believe that men older than 70 years should be carefully counseled about the declining benefits of prostate cancer detection with screening.


Subject(s)
Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/therapy , Age Factors , Aged, 80 and over , History, 18th Century , Humans , Male , Mass Screening , Middle Aged , Monte Carlo Method , Prostatic Neoplasms/diagnosis
6.
J Infect Dis ; 191(9): 1427-34, 2005 May 01.
Article in English | MEDLINE | ID: mdl-15809900

ABSTRACT

BACKGROUND: The genetic diversity of human immunodeficiency virus type 1 (HIV-1) raises the question of whether vaccines that include a component to elicit antiviral T cell immunity based on a single viral genetic clade could provide cellular immune protection against divergent HIV-1 clades. Therefore, we quantified the cross-clade reactivity, among unvaccinated individuals, of anti-HIV-1 T cell responses to the infecting HIV-1 clade relative to other major circulating clades. METHODS: Cellular immune responses to HIV-1 clades A, B, and C were compared by standardized interferon- gamma enzyme-linked immunospot assays among 250 unvaccinated individuals, infected with diverse HIV-1 clades, from Brazil, Malawi, South Africa, Thailand, and the United States. Cross-clade reactivity was evaluated by use of the ratio of responses to heterologous versus homologous (infecting) clades of HIV-1. RESULTS: Cellular immune responses were predominantly focused on viral Gag and Nef proteins. Cross-clade reactivity of cellular immune responses to HIV-1 clade A, B, and C proteins was substantial for Nef proteins (ratio, 0.97 [95% confidence interval, 0.89-1.05]) and lower for Gag proteins (ratio, 0.67 [95% confidence interval, 0.62-0.73]). The difference in cross-clade reactivity to Nef and Gag proteins was significant (P<.0001). CONCLUSIONS: Cross-clade reactivity of cellular immune responses can be substantial but varies by viral protein.


Subject(s)
HIV Seropositivity/immunology , HIV-1/immunology , Immunity, Cellular , T-Lymphocytes/immunology , Adult , Consensus Sequence , Cross Reactions , Female , Gene Products, nef/chemistry , Gene Products, nef/genetics , Geography , HIV-1/classification , Humans , Male , Middle Aged , nef Gene Products, Human Immunodeficiency Virus
7.
J Pain ; 5(6): 344-56, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15336639

ABSTRACT

UNLABELLED: In preparation for clinical trials of a vaccine against herpes zoster (HZ), we conducted a prospective, observational study to evaluate (1) the Zoster Brief Pain Inventory (ZBPI), an HZ-specific questionnaire to quantify HZ pain and discomfort, (2) an operational definition of postherpetic neuralgia (PHN), and (3) a severity-duration measure of the burden of illness caused by HZ. HZ patients aged 60 years or older (n = 121) were enrolled within 14 days of rash onset and completed ZBPI, McGill Pain Questionnaire Present Pain Intensity (PPI), quality of life (QoL), and activities of daily living (ADL) questionnaires on a predetermined schedule. Reliability, measured by intraclass correlation coefficients within 14 days of rash onset, ranged between 0.63 and 0.78. ZBPI pain scores were strongly correlated with other pain measures, interference with ADL, and worsening QoL. The operational definition of PHN, a ZBPI pain score of 3 or greater occurring 90 or more days after rash onset, had high agreement with pain worse than mild on the PPI (kappa = 0.72). The ZBPI pain severity-duration measure had high correlations with severity-duration measures of ADL interference, worsening QoL, and other pain scales. These findings support the validity and utility of the ZBPI, the definition of PHN, and the severity-duration measure of the burden of HZ illness. PERSPECTIVE: Herpes zoster pain, as measured by the ZBPI severity-duration measure, is associated with impairment in daily living activities and quality of life. The ZBPI measure appears useful for quantifying herpes zoster pain, postherpetic neuralgia, and impairment in daily living activities for clinical trials of herpes zoster prevention.


Subject(s)
Herpes Zoster/epidemiology , Neuralgia/epidemiology , Pain Measurement , Ambulatory Care/methods , Ambulatory Care/psychology , Clinical Trials as Topic/methods , Female , Herpes Zoster/prevention & control , Herpes Zoster/psychology , Humans , Longitudinal Studies , Male , Neuralgia/prevention & control , Neuralgia/psychology , Pain Measurement/psychology , Pain Measurement/statistics & numerical data , Prospective Studies , Statistics, Nonparametric
8.
Am J Epidemiol ; 159(8): 721-31, 2004 Apr 15.
Article in English | MEDLINE | ID: mdl-15051581

ABSTRACT

The association between a mother's use of specific medications during pregnancy and lactation and neuroblastoma in her offspring was evaluated in a case-control study. Newly diagnosed cases of neuroblastoma (n=504) in the United States and Canada were identified between 1992 and 1994 at 139 hospitals affiliated with the Pediatric Oncology Group or the Children's Cancer Group clinical trial programs. One age-matched control was sampled from the community of each case by means of random digit dialing. Exposure information was ascertained retrospectively from mothers in a structured telephone interview. Odds ratios were estimated using conditional logistic regression, with adjustment for maternal sociodemographic factors. The results did not support an association between neuroblastoma and maternal exposure to diuretic agents, antiinfective agents, estrogens, progestins, sedatives, anticonvulsant drugs, or drugs that may form N-nitroso derivatives. Mothers of cases were more likely to report using medications containing opioid agonists while they were pregnant or nursing than were mothers of controls (odds ratio=2.4, 95% confidence interval: 1.3, 4.3). Specifically, more mothers of cases reported using medications containing codeine while pregnant or nursing than did mothers of controls (odds ratio=3.4, 95% confidence interval: 1.4, 8.4). This preliminary finding may be due to bias, confounding, or chance, and additional studies are needed for confirmation.


Subject(s)
Neuroblastoma/chemically induced , Prenatal Exposure Delayed Effects , Adult , Canada/epidemiology , Case-Control Studies , Child, Preschool , Codeine/adverse effects , Female , Humans , Infant , Infant, Newborn , Interviews as Topic , Logistic Models , Narcotics/adverse effects , Neuroblastoma/epidemiology , Pregnancy , Retrospective Studies , Risk Factors , United States/epidemiology
9.
Pharmacoepidemiol Drug Saf ; 12(5): 361-9, 2003.
Article in English | MEDLINE | ID: mdl-12899109

ABSTRACT

OBJECTIVES: Metabolic abnormalities including hyperlipidemia have developed in patients infected with the human immunodeficiency virus (HIV) after treatment with protease inhibitor drugs. It is unclear whether the deleterious effects on plasma triglyceride concentrations observed in patients receiving highly active antiretroviral therapy are a class effect of protease inhibitors. Hypertriglyceridemia may constitute a risk factor for cardiovascular disease. The purpose of this retrospective analysis of HIV-infected patients enrolled in three randomized, double-blind trials of indinavir therapy was to determine whether indinavir use was associated with a larger increase in triglyceride levels than treatment without a protease inhibitor. METHODS: Using a mixed-effects model, we compared average changes in nonfasting plasma triglyceride levels among randomized treatment groups for each protocol separately. RESULTS: The median increase in triglyceride levels during the 1st year of antiretroviral monotherapy was less with indinavir than with either zidovudine or stavudine. The combination of indinavir and nucleoside-analogue reverse-transcriptase inhibitors (NRTI) resulted in smaller increments in triglyceride levels than NRTI monotherapy. Indinavir also augmented the reduction in triglyceride levels observed with combination therapy using zidovudine and lamivudine in persons with far advanced HIV-infection. However, up to 7% of patients receiving a NRTI and indinavir experienced elevations of nonfasting triglyceride levels in excess of 750 mg/dl. CONCLUSIONS: On average, the combination of indinavir and NRTI therapy was not associated with a greater elevation of non-fasting triglyceride levels in HIV-infected men with at least moderately advanced immunosuppression than treatment with NRTI drugs alone.


Subject(s)
Antiretroviral Therapy, Highly Active/adverse effects , Immunocompromised Host/drug effects , Indinavir/pharmacology , Indinavir/therapeutic use , Reverse Transcriptase Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/therapeutic use , Triglycerides/adverse effects , Triglycerides/blood , Zidovudine/therapeutic use , Double-Blind Method , Drug Therapy, Combination , Humans , Male , Retrospective Studies , Risk Factors , Time Factors
10.
J Rheumatol ; 30(6): 1196-202, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12784389

ABSTRACT

OBJECTIVE: To compare all-cause mortality rates and the incidence of major vascular events among patients with rheumatoid arthritis (RA), osteoarthritis (OA) without RA, or no arthritis using the UK General Practice Research Database (GPRD) while adjusting for age and sex. Clinic-based studies have found that patients with RA have higher all-cause and cardiovascular (CV) mortality than those without RA, after adjusting for age and sex. Much smaller elevations in risk have been found in the few community-based studies that have addressed this question. METHODS: After excluding patients with a history of myocardial infarction or cerebrovascular events, we followed a retrospective cohort of patients 40 years and older from GPRD practices until the earliest of death, disenrollment, or the occurrence of an incident vascular event. Using Poisson regression we compared age and gender adjusted incidence rates for RA, OA, or no arthritis. RESULTS: Five hundred and ninety-four practices contributed 2.37 million patients (1.11 million men and 1.26 million women) to the analysis. Over a mean duration of followup of almost 5 years, age and gender adjusted all-cause mortality rates were 60 to 70% higher in patients with RA compared to patients with OA and those with no arthritis. For the various vascular endpoints, the age and gender adjusted incidence rates were 30 to 60% higher in patients with RA compared to both patients with OA and those with no arthritis during the study period. The rates in patients with OA and those with no arthritis were essentially the same. CONCLUSION: Compared to patients with OA and those with no arthritis, patients with RA had a higher age and gender adjusted incidence of all-cause mortality and of major vascular events during almost 5 years of followup.


Subject(s)
Arthritis, Rheumatoid/mortality , Cardiovascular Diseases/mortality , Osteoarthritis/mortality , Adult , Age Distribution , Aged , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Sex Distribution , United Kingdom/epidemiology
11.
Arch Intern Med ; 162(10): 1105-10, 2002 May 27.
Article in English | MEDLINE | ID: mdl-12020179

ABSTRACT

BACKGROUND: Naproxen strongly inhibits platelet aggregation. OBJECTIVE: To examine the risk of acute thromboembolic cardiovascular events (TCEs) (myocardial infarction, sudden death, and stroke) with current naproxen use among patients with rheumatoid arthritis. METHODS: We studied patients aged 40 to 79 years with rheumatoid arthritis in the British General Practice Research Database, excluding those with a prior TCE and potentially confounding conditions. We matched up to 4 controls by sex, age, and site of medical practice to cases with first incident TCEs. The case diagnosis date was designated as the index date for each case and his or her controls. We categorized naproxen according to the most recent prescription prior to the index date as being current (< or =30 days), past (> 30 days but < 365 days), or none (> or =365 days before index date). Using conditional logistic regression, we conducted a matched case-control analysis with adjustment for potential confounders. RESULTS: We identified 809 cases. Current naproxen use was more common among controls (5.7%) than cases (3.2%). Adjusting for calendar year of treatment start, systemic corticosteroid use, diabetes, and comorbidity, we found that the odds ratio (95% confidence interval) for current naproxen use was 0.61 (0.39-0.94) while that for past use was 0.87 (0.65-1.16). Secondary and sensitivity analyses supported these results. CONCLUSIONS: In this case-control study, patients with rheumatoid arthritis and a current prescription for naproxen had a reduced risk of acute major TCEs relative to those with no naproxen prescription in the past year. These results are consistent with the ability of naproxen to inhibit platelet aggregation.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Myocardial Infarction/epidemiology , Naproxen/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Thromboembolism/epidemiology , Adult , Aged , Arthritis, Rheumatoid/complications , Case-Control Studies , England/epidemiology , Humans , Matched-Pair Analysis , Middle Aged , Multivariate Analysis , Myocardial Infarction/mortality , Myocardial Infarction/prevention & control , Regression Analysis , Risk , Survival Analysis , Thromboembolism/mortality , Thromboembolism/prevention & control , Wales/epidemiology
12.
Arch Intern Med ; 162(8): 936-42, 2002 Apr 22.
Article in English | MEDLINE | ID: mdl-11966346

ABSTRACT

BACKGROUND: Isolated case reports of gastric ulcers after alendronate sodium use raised concern about the gastroduodenal safety of daily alendronate. This study was conducted to estimate the excess risk of hospitalizations for gastric or duodenal perforations, ulcers, and bleeding associated with alendronate use. PARTICIPANTS AND METHODS: Study subjects were 6432 men and women, 35 years or older. The subjects were members of 8 health maintenance organizations who were dispensed alendronate from October 1995 through September 1997. There was also a group of 33 176 age-, sex-, and health maintenance organization-matched unexposed persons. Because of concerns that osteoporosis might confound the association between alendronate use and perforation, ulcer, or bleeding, a second comparison group of 9776 women, 60 years or older, who had osteoporotic fractures was assembled. Hospitalizations for gastroduodenal events were identified by discharge diagnosis codes in automated claims records, and confirmed by manual record review. RESULTS: Based on the 14 confirmed events in the alendronate group and 35 in the unexposed group, the crude incidence rate ratio of gastroduodenal perforation, ulcer, or bleeding for the alendronate cohort was 3.0. The incidence rate ratio was 1.8 (95% confidence interval, 0.8-3.9) after control for prior hospitalizations, comorbidity, and recent exposure to prescription nonsteroidal anti-inflammatory drugs and oral corticosteroids. The crude incidence ratio rate for the age, sex, and health maintenance organizations-restricted cohort of alendronate users relative to the fracture cohort was 1.1 and the adjusted incidence rate ratio was 1.1 (95% confidence interval, 0.6-2.2). CONCLUSIONS: Osteoporosis and related factors appear to play an important role in the relationship between alendronate use and confirmed gastroduodenal perforation, ulcer, or bleeding; a substantial fraction of the increased risk we observed for alendronate users in the unadjusted analysis was the result of confounding.


Subject(s)
Alendronate/administration & dosage , Alendronate/adverse effects , Duodenal Diseases/chemically induced , Duodenal Ulcer/chemically induced , Gastrointestinal Hemorrhage/chemically induced , Hospitalization , Intestinal Perforation/chemically induced , Stomach Ulcer/chemically induced , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Assessment
13.
J Clin Epidemiol ; 55(3): 279-84, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11864799

ABSTRACT

The objective of this article was to evaluate adult prescription recipients' choices among vaccine providers. The study setting was a cluster sample from 24 community pharmacies based on prescription records that suggested need for pneumococcal and influenza vaccines. Vaccination status, choice of vaccine provider, and opinions regarding vaccine providers were retrospectively surveyed by mail in spring 1999. Overall, 52% of survey recipients responded; 89% of respondents reported returning to the same type of vaccine provider in consecutive years. Two key factors affected choice of provider: convenience and provider experience. Convenience was a stronger factor for people younger than 65 taking chronic medications and those not vaccinated in the previous year. Most adult recipients of influenza vaccine returned to sites where they were vaccinated the previous year. Convenience was a major factor in vaccination decisions of adult prescription recipients.


Subject(s)
Attitude , Community Pharmacy Services/statistics & numerical data , Decision Making , Influenza Vaccines/administration & dosage , Pneumococcal Vaccines/administration & dosage , Adult , Aged , Factor Analysis, Statistical , Female , Humans , Male , Middle Aged , Oregon , Retrospective Studies
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