Routes to diagnosis and the association with the prognosis in patients with cancer – A nationwide register-based cohort study in Denmark

Background: The prognosis of cancer is related to how the cancer is identified, and where in the healthcare system the patient presents, i.e. routes to diagnosis (RtD). We aimed to describe the RtD for patients diagnosed with cancer in Denmark by using routinely collected register-based data and to investigate the association between RtD and prognosis measured as one-year all-cause mortality. / Methods: We conducted a population-based national cohort study by linking routinely collected Danish registry data. We categorised each patient into one of eight specified RtD based on an algorithm using a stepwise logic decision process. We described the proportions of patients with cancer diagnosed by different RtD. We examined associations between RtD and one-year all-cause mortality using logistic regression models adjusting for sex, age, cancer type, year of diagnosis, region of residence, and comorbidity. / Results: We included 144,635 cancers diagnosed in 139,023 patients in 2014–2017. The most common RtD were cancer patient pathway from primary care (45.9 %), cancer patient pathway from secondary care (20.0 %), unplanned hospital admission (15.8 %), and population-based screening (7.5 %). The one-year mortality ranged from 1.4 % in screened patients to 53.0 % in patients diagnosed through unplanned hospital admission. Patients with an unplanned admission were more likely to die within the first year after diagnosis (OR = 3.38 (95 %CI: 3.24–3.52)) compared to patients diagnosed through the cancer patient pathway from primary care. / Conclusion: The majority of cancer patients were diagnosed through a cancer patient pathway. The RtD were associated with the prognosis, and the prognosis was worst in patients diagnosed through unplanned admission. The study suggests that linking routinely collected registry data could enable a national framework for RtD, which could serve to identify variations across patient-, health-, and system-related and healthcare factors. This information could be used in future research investigating markers for monitoring purposes

Assessing how routes to diagnosis vary by the age of patients with cancer: a nationwide register-based cohort study in Denmark

BACKGROUND: Older patients with cancer have poorer prognosis compared to younger patients. Moreover, prognosis is related to how cancer is identified, and where in the healthcare system patients present, i.e. routes to diagnosis (RtD). We investigated whether RtD varied by patients' age. METHODS: This population-based national cohort study used Danish registry data. Patients were categorized into age groups and eight mutually exclusive RtD. We employed multinomial logistic regressions adjusted for sex, region, diagnosis year, cohabitation, education, income, immigration status and comorbidities. Screened and non-screened patients were analysed separately. RESULTS: The study included 137,876 patients. Both younger and older patients with cancer were less likely to get diagnosed after a cancer patient pathways referral from primary care physician compared to middle-aged patients. Older patients were more likely to get diagnosed via unplanned admission, death certificate only, and outpatient admission compared to younger patients. The patterns were similar across comorbidity levels. CONCLUSIONS: RtD varied by age groups, and middle-aged patients were the most likely to get diagnosed after cancer patient pathways with referral from primary care. Emphasis should be put on raising clinicians' awareness of cancer being the underlying cause of symptoms in both younger patients and in older patients

IgG Antibodies against Measles, Rubella, and Varicella Zoster Virus Predict Conversion to Multiple Sclerosis in Clinically Isolated Syndrome

BACKGROUND:Multiple sclerosis (MS) is characterized by a polyspecific B-cell response to neurotropic viruses such as measles, rubella and varicella zoster, with the corresponding antibodies measurable in CSF as the so-called "MRZ reaction" (MRZR). We aimed to evaluate the relevance of MRZR to predict conversion of patients with clinically isolated syndrome (CIS) to MS, and to compare it to oligoclonal bands (OCB) and MRI. METHODOLOGY/PRINCIPAL FINDINGS:MRZR was determined in a prospective study over 2 years including 40 patients that remained CIS over follow-up (CIS-CIS) and 49 patients that developed MS (CIS-RRMS) using ELISA. Using logistic regression, a score (MRZS) balancing the predictive value of the antibody indices included in MRZR was defined (9 points measles, 8 points rubella, 1 point varicella zoster, cutpoint: sum of scores greater 10). MRZR and MRZS were significantly more frequent in CIS-RRMS as compared to CIS-CIS (p=0.04 and p=0.02). MRZS showed the best positive predictive value (PPV) of all parameters investigated (79%, 95%-CI: 54-94%), which could be further increased by combination with MRI (91%, 95%-CI: 59-99%). CONCLUSIONS/SIGNIFICANCE:Our data indicate the relevance of MRZR to predict conversion to MS. It furthermore shows the importance of weighting the different antibody indices included in MRZR and suggest that patients with positive MRZR are candidates for an early begin of immunomodulatory therapy

GxE Interaction Influences Trajectories of Hand Grip Strength

Age-related decline in grip strength predicts later life disability, frailty, lower well-being and cognitive change. While grip strength is heritable, genetic influence on change in grip strength has been relatively ignored, with non-shared environmental influence identified as the primary contributor in a single longitudinal study. The extent to which gene-environment interplay, particularly gene-environment interactions, contributes to grip trajectories has yet to be examined. We considered longitudinal grip strength measurements in seven twin studies of aging in the Interplay of Genes and Environment across Multiple Studies consortium. Growth curve parameters were estimated for same-sex pairs, aged 34–99 (N = 10,681). Fisher’s test for mixture distribution of within-monozygotic twin-pair differences (N = 1724) was performed on growth curve parameters. We observed significant gene-environment interaction on grip strength trajectories. Finally, we compared the variability of within-pair differences of growth curve parameters by APOE haplotypes. Though not statistically significant, the results suggested that APOE ɛ2ɛ2/ɛ2ɛ3 haplotypes might buffer environmental influences on grip strength trajectories.peerReviewe

Associations between a polymorphism in the pleiotropic GCKR and Age-related phenotypes: the HALCyon programme.

Background: The glucokinase regulatory protein encoded by GCKR plays an important role in glucose metabolism and a single nucleotide polymorphism (SNP) rs1260326 (P446L) in the gene has been associated with several age-related biomarkers, including triglycerides, glucose, insulin and apolipoproteins. However, associations between SNPs in the gene and other ageing phenotypes such as cognitive and physical capability have not been reported. Methods: As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, men and women from five UK cohorts aged between 44 and 90+ years were genotyped for rs1260326. Meta-analysis was used to pool within-study genotypic associations between the SNP and several age-related phenotypes, including body mass index (BMI), blood lipid levels, lung function, and cognitive and physical capability. Results: We confirm the associations between the minor allele of the SNP and higher triglycerides and lower glucose levels. We also observed a triglyceride-independent association between the minor allele and lower BMI (pooled beta on zscore = 20.04, p-value = 0.0001, n = 16,251). Furthermore, there was some evidence for gene-environment interactions, including physical activity attenuating the effects on triglycerides. However, no associations were observed with measures of cognitive and physical capability. Conclusion: Findings from middle-aged to older adults confirm associations between rs1260326 GCKR and triglycerides and glucose, suggest possible gene-environment interactions, but do not provide evidence that its relevance extends to cognitive and physical capability