Risk of Several Cancers is Higher in Urban Areas after Adjusting for Socioeconomic Status. Results from a Two-Country Population-Based Study of 18 Common Cancers

Some studies suggest that there are urban-rural variations in cancer incidence but whether these simply reflect urban-rural socioeconomic variation is unclear. We investigated whether there were urban-rural variations in the incidence of 18 cancers, after adjusting for socioeconomic status. Cancers diagnosed between 1995 and 2007 were extracted from the population-based National Cancer Registry Ireland and Northern Ireland Cancer Registry and categorised by urban-rural status, based on population density of area of residence at diagnosis (rural 15 people per hectare). Relative risks (RR) were calculated by negative binomial regression, adjusting for age, country and three area-based markers of socioeconomic status. Risks were significantly higher in both sexes in urban than rural residents with head and neck (males RR urban vs. rural = 1.53, 95 % CI 1.42-1.64; females RR = 1.29, 95 % CI 1.15-1.45), esophageal (males 1.21, 1.11-1.31; females 1.21, 1.08-1.35), stomach (males 1.36, 1.27-1.46; females 1.19, 1.08-1.30), colorectal (males 1.14, 1.09-1.18; females 1.04, 1.00-1.09), lung (males 1.54, 1.47-1.61; females 1.74, 1.65-1.84), non-melanoma skin (males 1.13, 1.10-1.17; females 1.23, 1.19-1.27) and bladder (males 1.30, 1.21-1.39; females 1.31, 1.17-1.46) cancers. Risks of breast, cervical, kidney and brain cancer were significantly higher in females in urban areas. Prostate cancer risk was higher in rural areas (0.94, 0.90-0.97). Other cancers showed no significant urban-rural differences. After adjusting for socioeconomic variation, urban-rural differences were evident for 12 of 18 cancers. Variations in healthcare utilization and known risk factors likely explain some of the observed associations. Explanations for others are unclear and, in the interests of equity, warrant further investigation. © 2014 The New York Academy of Medicine.

Digoxin use after diagnosis of breast cancer and survival: a population-based cohort study

<p>Digoxin has been shown to have an estrogenic effect and is associated with increased risk of gynecomastia and estrogen-sensitive cancers such as breast and uterus cancer. These findings, particularly recent observations of increased breast cancer risk, raise questions about the safety of digoxin use in breast cancer patients. Therefore, we investigated whether digoxin use after breast cancer diagnosis increased the risk of breast cancer-specific mortality in breast cancer patients. A cohort of 17,842 breast cancer patients newly diagnosed from 1998 to 2009 was identified from English cancer registries (from the National Cancer Data Repository). This cohort was linked to the UK Clinical Practice Research Datalink (to provide digoxin and other prescription records) and to the Office of National Statistics mortality data (to identify breast cancer-specific deaths). Using time-dependent Cox regression models, unadjusted and adjusted hazard ratios (HR) and 95 % confidence intervals (CIs) were calculated for the association between post-diagnostic exposure to digoxin and breast cancer-specific and all-cause mortality. In 17,842 breast cancer patients, there were 2219 breast cancer-specific deaths. Digoxin users appeared to have increased breast cancer-specific mortality compared with non-users (HR 1.73; 95 % CI 1.39–2.15) but this association was entirely attenuated after adjustment for potential confounders (adjusted HR 0.91; 95 % CI 0.72–1.14). In this large population-based breast cancer cohort study, there was little evidence of an increase in breast cancer-specific mortality with digoxin use after diagnosis. These results provide some reassurance that digoxin use is safe in breast cancer patients.</p>

Recipient obesity and outcomes after kidney transplantation: a systematic review and meta-analysis

<p>BACKGROUND: The prevalence of obesity is increasing globally and is associated with chronic kidney disease and premature mortality. However, the impact of recipient obesity on kidney transplant outcomes remains unclear. This study aimed to investigate the association between recipient obesity and mortality, death-censored graft loss and delayed graft function (DGF) following kidney transplantation.</p><p>METHODS: A systematic review and meta-analysis was conducted using Medline, Embase and the Cochrane Library. Observational studies or randomized controlled trials investigating the association between recipient obesity at transplantation and mortality, death-censored graft loss and DGF were included. Obesity was defined as a body mass index (BMI) of ≥30 kg/m(2). Obese recipients were compared with those with a normal BMI (18.5-24.9 kg/m(2)). Pooled estimates of hazard ratios (HRs) for patient mortality or death-censored graft loss and odds ratios (ORs) for DGF were calculated.</p><p>RESULTS: Seventeen studies including 138 081 patients were analysed. After adjustment, there was no significant difference in mortality risk in obese recipients [HR = 1.24, 95% confidence interval (CI) = 0.90-1.70, studies = 5, n = 83 416]. However, obesity was associated with an increased risk of death-censored graft loss (HR = 1.06, 95% CI = 1.01-1.12, studies = 5, n = 83 416) and an increased likelihood of DGF (OR = 1.68, 95% CI = 1.39-2.03, studies = 4, n = 28 847).</p><p>CONCLUSIONS: Despite having a much higher likelihood of DGF, obese transplant recipients have only a slightly increased risk of graft loss and experience similar survival to recipients with normal BMI.</p>

Metformin use and survival after colorectal cancer: A population-based cohort study.

Preclinical evidence suggests that metformin could delay cancer progression. Previous epidemiological studies however have been limited by small sample sizes and certain time-related biases. This study aimed to investigate whether colorectal cancer patients with type 2 diabetes who were exposed to metformin had reduced cancer-specific mortality. We conducted a retrospective cohort study of 1,197 colorectal cancer patients newly diagnosed from 1998 to 2009 (identified from English cancer registries) with type 2 diabetes (based upon Clinical Practice Research Datalink, CPRD, prescription and diagnosis records). In this cohort 382 colorectal cancer-specific deaths occurred up to 2012 from the Office of National Statistics (ONS) mortality data. Metformin use was identified from CPRD prescription records. Using time-dependent Cox regression models, unadjusted and adjusted hazard ratios (HR) and 95% CIs were calculated for the association between post-diagnostic exposure to metformin and colorectal cancer-specific mortality. Overall, there was no evidence of an association between metformin use and cancer-specific death before or after adjustment for potential confounders (adjusted HR 1.06, 95% CI 0.80, 1.40). In addition, after adjustment for confounders, there was also no evidence of associations between other diabetic medications and cancer-specific mortality including sulfonylureas (HR 1.14, 95% CI 0.86, 1.51), insulin use (HR 1.35, 95% CI 0.95, 1.93) or other anti-diabetic medications including thiazolidinediones (HR 0.73, 95% CI 0.46, 1.14). Similar associations were observed by duration of use and for all-cause mortality. This population-based study, the largest to date, does not support a protective association between metformin and survival in colorectal cancer patients.

A HuGE Review and Meta-Analyses of Genetic Associations in New Onset Diabetes after Kidney Transplantation

<p>PURPOSE: New onset diabetes after transplantation (NODAT) is a serious complication following solid organ transplantation. There is a genetic contribution to NODAT and we have conducted comprehensive meta-analysis of available genetic data in kidney transplant populations.</p><p>METHODS: Relevant articles investigating the association between genetic markers and NODAT were identified by searching PubMed, Web of Science and Google Scholar. SNPs described in a minimum of three studies were included for analysis using a random effects model. The association between identified variants and NODAT was calculated at the per-study level to generate overall significance values and effect sizes.</p><p>RESULTS: Searching the literature returned 4,147 citations. Within the 36 eligible articles identified, 18 genetic variants from 12 genes were considered for analysis. Of these, three were significantly associated with NODAT by meta-analysis at the 5% level of significance; CDKAL1 rs10946398 p = 0.006 OR = 1.43, 95% CI = 1.11-1.85 (n = 696 individuals), KCNQ1 rs2237892 p = 0.007 OR = 1.43, 95% CI = 1.10-1.86 (n = 1,270 individuals), and TCF7L2 rs7903146 p = 0.01 OR = 1.41, 95% CI = 1.07-1.85 (n = 2,967 individuals).</p><p>CONCLUSION: Evaluating cumulative evidence for SNPs associated with NODAT in kidney transplant recipients has revealed three SNPs associated with NODAT. An adequately powered, dense genome-wide association study will provide more information using a carefully defined NODAT phenotype.</p>

A pilot study to develop an assessment tool for sheep welfare after long journey transport

<p>Sheep transport within Europe involves 9.5 million animals yearly, 63% of which travel over longjourneys (&gt; 8 h). Livestock transport, particularly over long journeys, gives rise to concern about the welfare of transported animals. The European Commission stimulates the development of market-oriented animal welfare standards for all phases of livestock production, providing an alternative to the 'regulatory approach'. This study aimed to develop and test a new sheep welfare assessment protocol to be used following transport, irrespective of the journey purpose. The protocol included outcome (animal-based measures) and input variables (resource-based and management-based measures), being welfare-relevant aspects of both transport and unloading procedures. Weighted Cohen's Kappa and Heiss' Kappa index of agreement were calculated to evaluate the raters accuracy and the inter-observer reliability.Overall, good agreement levels were found. The protocol was tested on 40 commercial transports arriving at previously selected assembly centres and slaughterhouses in Italy and Greece. The protocol was found to be feasible when applied to commercial transports, allowing for a comprehensive and quick sheep welfare assessment during unloading, without impairing stockman work. Univariate analysis was carried out to evaluate associations between outcome and input variables. In this study, significant association between outcome measures and risk factors were identified when associated to unloading procedures but not to travel conditions. In collaboration with the relevant stakeholders, this protocol might be developed into a tool for routine checks for certification purposes and could provide direct feedback to all professionals involved in animal transportation on the weaknesses and strengths of their work.</p>

Visual symptoms and retinal straylight after laser peripheral iridotomy: the Zhongshan Angle-Closure Prevention Trial.

OBJECTIVE: To assess the impact of laser peripheral iridotomy (LPI) on forward-scatter of light and subjective visual symptoms and to identify LPI parameters influencing these phenomena. DESIGN: Cohort study derived from a randomized trial, using an external control group. PARTICIPANTS: Chinese subjects initially aged 50 or older and 70 years or younger with bilateral narrow angles undergoing LPI in 1 eye selected at random, and age- and gender-matched controls. METHODS: Eighteen months after laser, LPI-treated subjects underwent digital iris photography and photogrammetry to characterize the size and location of the LPI, Lens Opacity Classification System III cataract grading, and measurement of retinal straylight (C-Quant; OCULUS, Wetzlar, Germany) in the treated and untreated eyes and completed a visual symptoms questionnaire. Controls answered the questionnaire and underwent straylight measurement and (in a random one-sixth sample) cataract grading. MAIN OUTCOME MEASURES: Retinal straylight levels and subjective visual symptoms. RESULTS: Among 230 LPI-treated subjects (121 [58.8%] with LPI totally covered by the lid, 43 [19.8%] with LPI partly covered by the lid, 53 [24.4%] with LPI uncovered by the lid), 217 (94.3%) completed all testing, as did 250 (93.3%) of 268 controls. Age, gender, and prevalence of visual symptoms did not differ between treated subjects and controls, although nuclear (P&lt;0.01) and cortical (P = 0.03) cataract were less common among controls. Neither presenting visual acuity nor straylight score differed between the treated and untreated eyes among all treated persons, nor among those (n = 96) with LPI partially or totally uncovered. Prevalence of subjective glare did not differ significantly between participants with totally covered LPI (6.61%; 95% confidence interval [CI], 3.39%-12.5%), partially covered LPI (11.6%; 95% CI, 5.07%-24.5%), or totally uncovered LPI (9.43%; 95% CI, 4.10%-10.3%). In regression models, only worse cortical cataract grade (P = 0.01) was associated significantly with straylight score, and no predictors were associated with subjective glare. None of the LPI size or location parameters were associated with straylight or subjective symptoms. CONCLUSIONS: These results suggests that LPI is safe regarding measures of straylight and visual symptoms. This randomized design provides strong evidence that treatment programs for narrow angles would be unlikely to result in important medium-term visual disability.

Effect of technique on intraocular pressure after combined cataract and glaucoma surgery: An evidence-based review.

TOPIC: <br/><br/>To analyze the literature pertaining to the techniques used in combined cataract and glaucoma surgery, including the technique of cataract extraction, the timing of the surgery (staged procedure versus combined procedure), the anatomic location of the operation, and the use of antifibrosis agents.<br/><br/>CLINICAL RELEVANCE: <br/><br/>Cataract and glaucoma are both common conditions and are often present in the same patient. There is no agreement concerning the optimal surgical management of these disorders when they coexist.<br/><br/>METHODS/LITERATURE REVIEWED: <br/><br/>Electronic searches of English language articles published since 1964 were conducted in Pub MED and CENTRAL, the Cochrane Collaboration's database. These were augmented by a hand search of six ophthalmology journals and the reference lists of a sample of studies included in the literature review. Evidence grades (A, strong; B, moderate; C, weak; I, insufficient) were assigned to the evidence that involved a direct comparison of alternative techniques.<br/><br/>RESULTS: <br/><br/>The preponderance of evidence from the literature suggests a small (2-4 mmHg) benefit from the use of mitomycin-C (MMC), but not 5-fluorouracil (5-FU), in combined cataract and glaucoma surgery (evidence grade B). Two-site surgery provides slightly lower (1-3 mmHg) intraocular pressure (IOP) than one-site surgery (evidence grade C), and IOP is lowered more (1-3 mmHg) by phacoemulsification than by nuclear expression in combined procedures (evidence grade C). There is insufficient evidence to conclude either that staged or combined procedures give better results or that alternative glaucoma procedures are superior to trabeculectomy in combined procedures.<br/><br/>CONCLUSIONS: <br/><br/>In the literature on surgical techniques and adjuvants used in the management of coexisting cataract and glaucoma, the strongest evidence of efficacy exists for using MMC, separating the incisions for cataract and glaucoma surgery, and removing the nucleus by phacoemulsification.<br/>

Cataract after glaucoma filtration surgery.

PURPOSE: <br/><br/>We reviewed the evidence regarding cataract incidence and progression after glaucoma surgery.<br/><br/>DESIGN: <br/><br/>Evidence-based review of available literature.<br/><br/>METHODS: <br/><br/>We performed a systematic review of relevant studies published in English.<br/><br/>RESULTS: <br/><br/>Reports of visually significant cataract after glaucoma surgery are supported by data from randomized clinical trials and large case series.<br/><br/>CONCLUSIONS: <br/><br/>Patients undergoing glaucoma surgery are at increased risk for the development and progression of cataract.<br/>

Determinants and heritability of intraocular pressure and cup-to-disc ratio in a defined older population.

PURPOSE: <br/><br/>To investigate the heritability of intraocular pressure (IOP) and cup-to-disc ratio (CDR) in an older well-defined population.<br/><br/>DESIGN: <br/><br/>Family-based cohort study.<br/><br/>PARTICIPANTS: <br/><br/>Through the population-based Salisbury Eye Evaluation study, we recruited 726 siblings (mean age, 74.7 years) in 284 sibships.<br/><br/>METHODS: <br/><br/>Intraocular pressure and CDR were measured bilaterally for all participants. The presence or absence of glaucoma was determined by a glaucoma specialist for all probands on the basis of visual field, optic nerve appearance, and history. The heritability of IOP was calculated as twice the residual between-sibling correlation of IOP using linear regression and generalized estimating equations after adjusting for age, gender, mean arterial pressure, race, self-reported diabetes status, and history of systemic steroid use. The heritability of CDR was calculated using the same model and adjustments as above, while also adjusting for IOP.<br/><br/>MAIN OUTCOME MEASURES: <br/><br/>Heritability and determinants of IOP and CDR, and impact of siblings' glaucoma status on IOP and CDR.<br/><br/>RESULTS: <br/><br/>We estimated the heritability to be 0.29 (95% confidence interval [CI], 0.12-0.46) for IOP and 0.56 (95% CI, 0.35-0.76) for CDR in this population. Mean IOP in siblings of glaucomatous probands was statistically significantly higher than in siblings of normal probands (mean difference, 1.02 mmHg; P = 0.017). The mean CDR in siblings of glaucomatous probands was 0.07 (or 19%) larger than in siblings of glaucoma suspect referrals (P = 0.045) and siblings of normal probands (P = 0.004).<br/><br/>CONCLUSIONS: <br/><br/>In this elderly population, we found CDR to be highly heritable and IOP to be moderately heritable. On average, siblings of glaucoma patients had higher IOPs and larger CDRs than siblings of nonglaucomatous probands.<br/>

Statin use after diagnosis of breast cancer and survival: a population-based cohort study

<p>BACKGROUND: Preclinical studies have shown that statins, particularly simvastatin, can prevent growth in breast cancer cell lines and animal models. We investigated whether statins used after breast cancer diagnosis reduced the risk of breast cancer-specific, or all-cause, mortality in a large cohort of breast cancer patients.</p><p>METHODS: A cohort of 17,880 breast cancer patients, newly diagnosed between 1998 and 2009, was identified from English cancer registries (from the National Cancer Data Repository). This cohort was linked to the UK Clinical Practice Research Datalink, providing prescription records, and to the Office of National Statistics mortality data (up to 2013), identifying 3694 deaths, including 1469 deaths attributable to breast cancer. Unadjusted and adjusted hazard ratios (HRs) for breast cancer-specific, and all-cause, mortality in statin users after breast cancer diagnosis were calculated using time-dependent Cox regression models. Sensitivity analyses were conducted using multiple imputation methods, propensity score methods and a case-control approach.</p><p>RESULTS: There was some evidence that statin use after a diagnosis of breast cancer had reduced mortality due to breast cancer and all causes (fully adjusted HR = 0.84 [95% confidence interval = 0.68-1.04] and 0.84 [0.72-0.97], respectively). These associations were more marked for simvastatin 0.79 (0.63-1.00) and 0.81 (0.70-0.95), respectively.</p><p>CONCLUSIONS: In this large population-based breast cancer cohort, there was some evidence of reduced mortality in statin users after breast cancer diagnosis. However, these associations were weak in magnitude and were attenuated in some sensitivity analyses.</p>

Digoxin use after diagnosis of colorectal cancer and survival: a population-based cohort study.

BACKGROUND: <br/><br/>Digoxin has been shown to affect a number of pathways that are of relevance to cancer, and its use has been associated with increased risks of breast and uterus cancer and, more recently, a 40% increase in colorectal cancer risk. These findings raise questions about the safety of digoxin use in colorectal cancer patients, and, therefore, we investigated whether digoxin use after colorectal cancer diagnosis increased the risk of colorectal cancer-specific mortality.<br/><br/>METHODS: <br/><br/>A cohort of 10,357 colorectal cancer patients newly diagnosed from 1998 to 2009 was identified from English cancer registries and linked to the UK Clinical Practice Research Datalink (to provide digoxin and other prescription records) and to the Office of National Statistics mortality data (to identify 2,724 colorectal cancer-specific deaths). Using time-dependent Cox regression models, unadjusted and adjusted HRs and 95% confidence intervals (CI) were calculated for the association between postdiagnostic exposure to digoxin and colorectal cancer-specific mortality.<br/><br/>RESULTS: <br/><br/>Overall, 682 (6%) colorectal cancer patients used digoxin after diagnosis. Digoxin use was associated with a small increase in colorectal cancer-specific mortality before adjustment (HR, 1.25; 95% CI, 1.07-1.46), but after adjustment for confounders, the association was attenuated (adjusted HR, 1.10; 95% CI, 0.91-1.34) and there was no evidence of a dose response.<br/><br/>CONCLUSIONS: <br/><br/>In this large population-based colorectal cancer cohort, there was little evidence of an increase in colorectal cancer-specific mortality with digoxin use after diagnosis.<br/><br/>IMPACT: <br/><br/>These results provide some reassurance that digoxin use is safe in colorectal cancer patients.<br/>

Health systems efficiency after the crisis in the OECD

This work evaluates the efficiency position of the health system of each OECD country. It identifies whether, or not, health systems changed in terms of quality and performance after the financial crisis. The health systems performance was calculated by fixed-effects estimator and by stochastic frontier analysis. The results suggest that many of those countries that the crisis affected the most are more efficient than the OECD average. In addition, some of those countries even managed to reach the top decile in the efficiency ranking. Finally, we analyze the stochastic frontier efficiency scores together with other health indicators to evaluate the health systems’ overall adjustments derived from the crisis.

Y-90-Ibritumomab Tiuxetan (Zevalin (R)) Consolidation of First Remission In Advanced-Stage Follicular Non-Hodgkin's Lymphoma: Updated Results After a Median Follow-up of 66.2 Months From the International, Randomized, Phase III First-Line Indolent Trial (FIT) In 414 Patients

The FIT trial was conducted to evaluate the safety and efficacy of 90Y-ibritumomab tiuxetan (0.4 mCi/kg; maximum dose 32 mCi) when used as consolidation of first complete or partial remission in patients with previously untreated, advanced-stage follicular lymphoma (FL). Patients were randomly assigned to either 90Y-ibritumomab treatment (n = 207) or observation (n = 202) within 3 months (mo) of completing initial induction therapy (chemotherapy only: 86%; rituximab in combination with chemotherapy: 14%). Response status prior to randomization did not differ between the groups: 52% complete response (CR)/CR unconfirmed (CRu) to induction therapy and 48% partial response (PR) in the 90Y-ibritumomab arm vs 53% CR/CRu and 44% PR in the control arm. The primary endpoint was progression-free survival (PFS) of the intent-to-treat (ITT) population. Results from the first extended follow-up after a median of 3.5 years revealed a significant improvement in PFS from the time of randomization with 90Y-ibritumomab consolidation compared with control (36.5 vs 13.3 mo, respectively; P &lt; 0.0001; Morschhauser et al. JCO. 2008; 26:5156-5164). Here we report a median follow-up of 66.2 mo (5.5 years). Five-year PFS was 47% in the 90Y-ibritumomab group and 29% in the control group (hazard ratio (HR) = 0.51, 95% CI 0.39-0.65; P &lt; 0.0001). Median PFS in the 90Y-ibritumomab group was 49 mo vs 14 mo in the control group. In patients achieving a CR/CRu after induction, 5-year PFS was 57% in the 90Y-ibritumomab group, and the median had not yet been reached at 92 months, compared with a 43% 5-year PFS in the control group and a median of 31 mo (HR = 0.61, 95% CI 0.42-0.89). For patients in PR after induction, the 5-year PFS was 38% in the 90Y-ibritumomab group with a median PFS of 30 mo vs 14% in the control group with a median PFS of 6 mo (HR = 0.38, 95% CI 0.27-0.53). Patients who had received rituximab as part of induction treatment had a 5-year PFS of 64% in the 90Y-ibritumomab group and 48% in the control group (HR = 0.66, 95% CI 0.30-1.47). For all patients, time to next treatment (as calculated from the date of randomization) differed significantly between both groups; median not reached at 99 mo in the 90Y-ibritumomab group vs 35 mo in the control group (P &lt; 0.0001). The majority of patients received rituximab-containing regimens when treated after progression (63/82 [77%] in the 90Y-ibritumomab group and 102/122 [84%] in the control group). Overall response rate to second-line treatment was 79% in the 90Y-ibritumomab group (57% CR/CRu and 22% PR) vs 78% in the control arm (59% CR/CRu, 19% PR). Five-year overall survival was not significantly different between the groups; 93% and 89% in the 90Y-ibritumomab and control groups, respectively (P = 0.561). To date, 40 patients have died; 18 in the 90Y-ibritumomab group and 22 in the control group. Secondary malignancies were diagnosed in 16 patients in the 90Y-ibritumomab arm vs 9 patients in the control arm (P = 0.19). There were 6 (3%) cases of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) in the 90Y-ibritumomab arm vs 1 MDS in the control arm (P = 0.063). In conclusion, this extended follow-up of the FIT trial confirms the benefit of 90Y-ibritumomab consolidation with a nearly 3 year advantage in median PFS. A significant 5-year PFS improvement was confirmed for patients with a CR/CRu or a PR after induction. Effective rescue treatment with rituximab-containing regimens may explain the observed no difference in overall survival between both patient groups who were - for the greater part - rituximab-naïve.

Protección miocárdica con custodiol y trastornos de la osmolalidad

En análisis retrospectivo evaluamos 91 pacientes llevados a cirugía cardiaca entre 2013 y 2014 en la Fundación Cardioinfantil, en quienes se administro Custodiol, analizando los niveles de sodio y osmolalidad plasmática efectiva antes, durante y después del procedimiento quirúrgico. Nosotros evaluamos la relación entre administración de Custodiol y cambios en el sodio y osmolalidad plasmática del paciente llevado a cirugía cardiaca.