Joan Fortuny

Burden of illness of diabetic macular edema: literature review.

Abstract Objective: To provide an overview of the literature on the burden of diabetic macular edema (DME) in the United States and selected European countries. Research design and methods: Computerized searches of English-language literature were conducted in PubMed/MEDLINE (1980–2009). The searches were supplemented with electronic and manual searches of relevant society/association proceedings and bibliographies of electronically identified sources. Abstracts were reviewed for relevance to any of the following topics: epidemiology, including prevalence and incidence; health outcomes; resource use and treatment patterns; and economic and humanistic burden associated with DME. Relevant full text articles were retrieved and major findings were synthesized and compared within and across countries. Results: A total of 400 citations were included in the initial review. After abstract screening, 47 articles were deemed pertinent and summarized in this review. The prevalence of DME among diabetic patients ranged from 0.85% to 12.3% across the countries studied. The prevalence and incidence of DME vary depending on type of diabetes (1 vs. 2), insulin- vs. non-insulin-dependence, and duration of disease (years since diagnosis). Although literature findings are limited and indicate a need for further investigation, a synthesis of the available results indicates that DME has a negative impact on patients’ health-related quality of life. In addition, patients with DME consume significantly more healthcare resources and incur higher costs compared to diabetic patients without retinal complications. Conclusions: There remains a need for consistent data capture and assessment within and between countries included in this analysis. Despite the limited evidence, DME appears to be a costly disease that has a negative impact on patients’ quality of life.

Risk of Endometrial Cancer in Relation to Medical Conditions and Medication Use

We studied the relation of medical conditions related to obesity and medications used for these conditions with endometrial cancer. We also investigated the association of other medical conditions and medications with risk. This U.S. population-based case-control study included 469 endometrial cancer cases and 467 controls. Information on putative risk factors for endometrial cancer was collected through personal interviews. We asked women about their medical history and medications used for six months or longer and the number of years each medication was taken. Risk was strongly associated with increasing obesity (P for trend < 0.001). Among the conditions related to obesity, and after adjustment for age, body mass index, and other risk factors and conditions, uterine fibroids were independently related to an increased cancer risk [adjusted odds ratio (OR), 1.8; 95% confidence interval (95% CI), 1.2-2.5]. Although hypertension was not significantly related to endometrial cancer after adjustment for age and body mass index, the use of thiazide diuretics was independently associated with increased risk (OR, 1.8; 95% CI, 1.1-3.0). Anemia was associated with decreased risk (OR, 0.6; 95% CI, 0.5-0.9). Use of nonsteroidal anti-inflammatory drugs was related to a decreased risk (OR, 0.7; 95% CI, 0.5-0.97). To our knowledge, the observation about thiazide diuretics is novel and requires confirmation in other studies and populations. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1448–56)

Glucocorticoid therapy and risk of bladder cancer.

Background:Use of immunosuppressive drugs post organ transplantation, and prolonged use of glucorticoids for other conditions have been associated with subsequent risk of certain malignancies, that is, skin cancers and lymphoma. There is evidence that the incidence of bladder cancer is also elevated among organ transplant recipients, however, it is unknown whether other groups of patients, that is, those taking oral glucocorticoids, likewise are at an increased risk.Methods:In a population-based case–control study in New Hampshire, USA, we compared the use of glucocorticoids in 786 bladder cancer cases and in 1083 controls. We used unconditional logistic regression analysis to compute adjusted odds ratios (ORs) associated with oral glucocorticoid use.Results:In our analysis, the risk of bladder cancer was related to a history of prolonged oral glucocorticoid use (OR=1.85, 95% CI=1.24–2.76, adjusted for age, gender and smoking). Associations with oral glucocorticoid use were stronger for invasive tumours (OR=2.12, 95% CI=1.17–3.85) and tumours with high (3+) p53 staining intensity (OR=2.35, 95% CI=1.26–4.36).Conclusion:Our results raise the possibility of an increased risk of bladder cancer from systemic use of glucocorticoids, and a potential role of immune surveillance in bladder cancer aetiology.

Use of Analgesics and Nonsteroidal Anti-inflammatory Drugs, Genetic Predisposition, and Bladder Cancer Risk in Spain

Background: We assessed use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAID), aspirin, paracetamol (acetaminophen), phenacetin, and metamizol (dipyrone) and risk of bladder cancer and their interaction with polymorphisms in drug-metabolizing genes. Methods: We analyzed personal interview data from 958 incident bladder cancer cases and 1,029 hospital controls from a multicenter case-control study in Spain. A drug matrix was developed to estimate cumulative lifetime dose of active ingredients. Polymorphisms in GSTP1, SULT1A1, CYP2E1, CYP2C9, and NAT2 were examined. Results: A significant reduction in bladder cancer risk [adjusted odds ratio (OR), 0.4; 95% confidence interval (95% CI), 0.2-0.9] was observed for regular users of nonaspirin NSAIDs compared with never users. Regular users of aspirin experienced no reduction in risk (OR, 1.0; 95% CI, 0.7-1.5). Regular users of paracetamol had no overall increased risk of bladder cancer (OR, 0.8; 95% CI, 0.4-1.3), but our data suggested a qualitative interaction with the GSTP1 I105V genotype. Subjects with at least one copy of the 359L or 144C variant alleles in the NSAID-metabolizing gene CYP2C9 had a slightly decreased risk of bladder cancer (OR, 0.8; 95% CI, 0.7-1.0; P = 0.037); however, having at least one copy of the 359L or 144C variant alleles did not significantly modify the protective effect of nonaspirin NSAID use. Conclusion: Regular use of nonaspirin NSAIDs was associated with a reduced risk of bladder cancer, which was not modified by polymorphisms in the NSAID-metabolizing gene CYP2C9. We found no evidence of an overall effect for paracetamol or aspirin use. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1696–703)

Analgesic and anti-inflammatory drug use and risk of bladder cancer: a population based case control study

BackgroundUse of phenacetin and other analgesic and non-steroidal anti-inflammatory drugs (NSAIDs) potentially influences bladder cancer incidence, but epidemiologic evidence is limited.MethodsWe analyzed data from 376 incident bladder cancer cases and 463 controls from a population-based case-control study in New Hampshire on whom regular use of analgesic drugs and NSAIDs was obtained. Odds ratios and 95% confidence intervals were computed using logistic regression with adjustment for potentially confounding factors. Separate models by tumor stage, grade and TP53 status were conducted.ResultsWe found an elevated odds ratio (OR) associated with reported use of phenacetin-containing medications, especially with longer duration of use (OR >8 years = 3.00, 95% confidence interval (CI) = 1.4–6.5). In contrast, use of paracetamol did not relate overall to risk of bladder cancer. We also found that regular use of any NSAID was associated with a statistically significant decrease in bladder cancer risk (OR = 0.6, 95% CI = 0.4–0.9), and specifically use of aspirin. Further, the association with NSAID use was largely among invasive, high grade and TP53 positive tumors.ConclusionWhile these agents have been investigated in several studies, a number of questions remain regarding the effects of analgesic and NSAID use on risk of bladder cancer.

Acetaminophen use in pregnancy and neurodevelopment: attention function and autism spectrum symptoms

Background Acetaminophen is extensively used during pregnancy. But there is a lack of population-representative cohort studies evaluating its effects on a range of neuropsychological and behavioural endpoints. We aimed to assess whether prenatal exposure to acetaminophen is adversely associated with neurodevelopmental outcomes at 1 and 5 years of age. Methods This Spanish birth cohort study included 2644 mother-child pairs recruited during pregnancy. The proportion of liveborn participants evaluated at 1 and 5 years was 88.8% and 79.9%, respectively. Use of acetaminophen was evaluated prospectively in two structured interviews. Ever/never use and frequency of use (never, sporadic, persistent) were measured. Main neurodevelopment outcomes were assessed using Childhood Autism Spectrum Test (CAST), Conners Kiddie Continuous Performance Test (K-CPT) and ADHD-DSM-IV form list. Regression models were adjusted for social determinants and co-morbidities. Results Over 40% of mothers reported using acetaminophen. Ever-exposed offspring had higher risks of presenting more hyperactivity/impulsivity symptoms [incidence rate ratio (IRR) = 1.41, 95% confidence interval (CI) 1.01-1.98), K-CPT commission errors (IRR = 1.10, 1.03-1.17), and lower detectability scores (coefficient β = -0.75, -0.13--0.02). CAST scores were increased in ever-exposed males (β = 0.63, 0.09-1.18). Increased effect sizes of risks by frequency of use were observed for hyperactivity/impulsivity symptoms (IRR = 2.01, 0.95-4.24) in all children, K-CPT commission errors (IRR = 1.32, 1.05-1.66) and detectability (β = -0.18, -0.36-0.00) in females, and CAST scores in males (β = 1.91, 0.44-3.38). Conclusions Prenatal acetaminophen exposure was associated with a greater number of autism spectrum symptoms in males and showed adverse effects on attention-related outcomes for both genders. These associations seem to be dependent on the frequency of exposure.

Incidence of retinal complications in a cohort of newly diagnosed diabetic patients.

Purpose We aimed at estimating the incidence of diabetic retinopathy (DR) and maculopathy (DMP) among newly diagnosed type 1 (t1DM) and type 2 diabetic patients (t2DM) in the United Kingdom primary care system. The incidence of DMP among patients with DR was also estimated. Method We conducted a cohort study using The Health Improvement Network database. The cohort included 64,983 incident diabetic patients (97.3% were t2DM) aged 1–84 years diagnosed between 2000 and 2007. This cohort was followed from the date of diabetes diagnosis until recording of DR or DMP in two separate follow-ups. Follow-up was censored at 85 years of age, death, or end of 2008. An additional follow-up was conducted from DR to DMP diagnosis using similar censoring reasons. DR and DMP cumulative incidences were calculated as well as incidence rates (IR; cases per 1,000 person-years) per calendar period (2000–2001 and 2006–2007). Results Follow-up for DR: 9 years after diabetes diagnosis, 28% of t2DM and 24% of t1DM patients had developed DR (7,899 incident DR cases). During the first 2 years with diabetes, the IR was almost 2 times higher in patients diagnosed with diabetes in 2006–2007 (47.7) than among those diagnosed in 2000–2001 (24.5). Follow-up for DMP: 9 years after diabetes diagnosis, 3.6% of t2DM and 4.4% of t2DM patients had developed DMP (912 incident DMP cases). During the first 2 years with diabetes, the IR was three times higher in patients diagnosed with diabetes in 2006–2007 (5.8) than among those diagnosed in 2000–2001 (1.8). Macular oedema occurred in 0.8% of patients. Conclusions In a cohort of incident diabetes, 28% of patients developed retinopathy and 4% maculopathy within the first 9 years. The 2-year IRs of DR and DMP were higher in patients diagnosed with diabetes during the period 2006–2007 than in those diagnosed during the 2000–2001 period.

Validation of Diabetic Retinopathy and Maculopathy Diagnoses Recorded in a U.K. Primary Care Database

OBJECTIVE To describe the validity of recorded diabetic retinopathy (DR) and diabetic maculopathy (DMP) diagnoses, including edema (DMO) in The Health Improvement Network (THIN) database. RESEARCH DESIGN AND METHODS In two independent computer searches, we detected 20,838 patients with diabetes aged 1–84 years with a first DR computer Read entry in 2000–2008 and 4,064 with a first DMP entry. A two-step strategy was used to validate both outcomes as follows: 1) review of patient profiles including free-text comments from primary care practitioners (PCPs) (containing referral information and test results) of a random sample of 500 DR and all DMP computer-detected patients. We classified them in probable, possible, and noncase according to the diagnosis plausibility based on the manual review of the computerized information; and 2) review of questionnaires sent by PCPs and medical records in a random sample (N = 200 for each outcome including 36 diabetic macular edema [DMO]). Gold standard was PCPs’ confirmation. RESULTS After profiles review, we categorized 418 as probable/possible DR. In addition, 3,676 DMP were categorized as probable/possible (including 711 DMO). After review of information sent by PCPs, confirmation rates were 87.3 and 87.2%, respectively (90.3% for DMO). When we applied them to the whole sample of computer-detected patients, the weighted confirmation rate was 78.0% for DR and 78.8% for DMP (86.2% for DMO). CONCLUSIONS Read codes for DR, DM, and DMO are moderately accurate in identifying incident case subjects of these ophthalmologic complications. The validity improved when incorporating PCPs’ text comments to the patient’s profile. THIN database proved to be a valuable resource to study ophthalmological diabetes complications.

Urinary pH, cigarette smoking and bladder cancer risk

Glucuronide conjugates of 4-aminobiphenyl and its N-hydroxy metabolite can be rapidly hydrolyzed in acidic urine to undergo further metabolic activation and form DNA adducts in the urothelium. We conducted a large multicenter case-control study in Spain to explore the etiology of bladder cancer and evaluated the association between urine pH and bladder cancer risk, alone and in combination with cigarette smoking. In total, 712 incident urothelial cell carcinoma cases and 611 hospital controls directly measured their urine pH with dipsticks twice a day (first void in the morning and early in the evening) during four consecutive days 2 weeks after hospital discharge. We found that a consistently acidic urine pH ≤6.0 was associated with an increased risk of bladder cancer [odds ratio (OR) = 1.5, 95% confidence interval (CI): 1.2-1.9] compared with all other subjects. Furthermore, risk estimates for smoking intensity and risk of bladder cancer among current smokers tended to be higher for those with a consistently acidic urine (OR = 8.8, 11.5 and 23.8) compared with those without (OR = 4.3, 7.7 and 5.8, respectively, for 1-19, 20-29 and 30+ cigarettes per day; P(interaction) for 30+ cigarettes per day = 0.024). These results suggest that urine pH, which is determined primarily by diet and body surface area, may be an important modifier of smoking and risk of bladder cancer.

Uso de analgésicos y ácido acetilsalicílico en un estudio multicéntrico en España

Objetivo: Evaluar el consumo de paracetamol, metamizol y acido acetilsalicilico (AAS) en un estudio multicentrico. Pacientes y metodo: Se analizaron los controles de un estudio de casos y controles hospitalarios (n = 1.029) sobre cancer vesical mediante la aplicacion de una matriz de medicamentos y principios activos. El motivo de ingreso de los controles no se asociaba con el uso cronico de analgesicos. Se utilizo un modelo de regresion logistica. Resultados: El uso cronico de AAS fue del 8%, el de paracetamol, del 5% y el de metamizol, del 2%. El AAS fue mas usado por personas con educacion secundaria o superior (odds ratio [OR] = 2,0, intervalo de confianza [IC] del 95%, 1,52-2,93). Las mujeres usaron mas paracetamol (OR = 1,91; IC del 95%, 1,30-2,80) y metamizol (OR = 2,80; IC del 95%, 1,49-4,47). Los menores de 65 anos usaron mas metamizol. Conclusion: El uso cronico de AAS y paracetamol es bajo comparado con el de Estados Unidos o el norte de Europa, aunque es parecido al del sur de Europa. Hay diferencias en el uso de analgesicos en funcion de las variables sociodemograficas.