Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

The effect of comorbidity on the use of adjuvant chemotherapy and survival from colon cancer: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Comorbidity has a well documented detrimental effect on cancer survival. However it is difficult to disentangle the direct effects of comorbidity on survival from indirect effects via the influence of comorbidity on treatment choice. This study aimed to assess the impact of comorbidity on colon cancer patient survival, the effect of comorbidity on treatment choices for these patients, and the impact of this on survival among those with comorbidity.</p> <p>Methods</p> <p>This retrospective cohort study reviewed 589 New Zealanders diagnosed with colon cancer in 1996–2003, followed until the end of 2005. Clinical and outcome data were obtained from clinical records and the national mortality database. Cox proportional hazards and logistic regression models were used to assess the impact of comorbidity on cancer specific and all-cause survival, the effect of comorbidity on chemotherapy recommendations for stage III patients, and the impact of this on survival among those with comorbidity.</p> <p>Results</p> <p>After adjusting for age, sex, ethnicity, area deprivation, smoking, stage, grade and site of disease, higher Charlson comorbidity score was associated with poorer all-cause survival (HR = 2.63 95%CI:1.82–3.81 for Charlson score ≥ 3 compared with 0). Comorbidity count and several individual conditions were significantly related to poorer all-cause survival. A similar, but less marked effect was seen for cancer specific survival. Among patients with stage III colon cancer, those with a Charlson score ≥ 3 compared with 0 were less likely to be offered chemotherapy (19% compared with 84%) despite such therapy being associated with around a 60% reduction in excess mortality for both all-cause and cancer specific survival in these patients.</p> <p>Conclusion</p> <p>Comorbidity impacts on colon cancer survival thorough both physiological burden of disease and its impact on treatment choices. Some patients with comorbidity may forego chemotherapy unnecessarily, increasing avoidable cancer mortality.</p

Genome-wide analysis of genetic loci associated with Alzheimer Disease

Context Genome-wide association studies (GWAS) have recently identified CLU, PICALM, and CR1 as novel genes for late-onset Alzheimer disease (AD). Objectives To identify and strengthen additional loci associated with AD and confirm these in an independent sample and to examine the contribution of recently identified genes to AD risk prediction in a 3-stage analysis of new and previously published GWAS on more than 35 000 persons (8371 AD cases). Design, Setting, and Participants In stage 1, we identified strong genetic associations (P < 10−3) in a sample of 3006 AD cases and 14 642 controls by combining new data from the population-based Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (1367 AD cases [973 incident]) with previously reported results from the Translational Genomics Research Institute and the Mayo AD GWAS. We identified 2708 single-nucleotide polymorphisms (SNPs) with P<10−3. In stage 2, we pooled results for these SNPs with the European AD Initiative (2032 cases and 5328 controls) to identify 38 SNPs (10 loci) with P<10−5. In stage 3, we combined data for these 10 loci with data from the Genetic and Environmental Risk in AD consortium (3333 cases and 6995 controls) to identify 4 SNPs with P<1.7×10−8. These 4 SNPs were replicated in an independent Spanish sample (1140 AD cases and 1209 controls). Genome-wide association analyses were completed in 2007-2008 and the meta-analyses and replication in 2009. Main Outcome Measure Presence of Alzheimer disease. Results Two loci were identified to have genome-wide significance for the first time: rs744373 near BIN1 (odds ratio [OR],1.13; 95% confidence interval [CI],1.06-1.21 per copy of the minor allele; P = 1.59×10−11) and rs597668 near EXOC3L2/BLOC1S3/MARK4 (OR, 1.18; 95% CI, 1.07-1.29; P = 6.45×10−9). Associations of these 2 loci plus the previously identified loci CLU and PICALM with AD were confirmed in the Spanish sample (P < .05). However, although CLU and PICALM were confirmed to be associated with AD in this independent sample, they did not improve the ability of a model that included age, sex, and APOE to predict incident AD (improvement in area under the receiver operating characteristic curve from 0.847 to 0.849 in the Rotterdam Study and 0.702 to 0.705 in the Cardiovascular Health Study). Conclusions Two genetic loci for AD were found for the first time to reach genome-wide statistical significance. These findings were replicated in an independent population. Two recently reported associations were also confirmed. These loci did not improve AD risk prediction. While not clinically useful, they may implicate biological pathways useful for future research