Monitoring inosine monophosphate dehydrogenase (IMPDH) activity as a biomarker of mycophenolic acid (MPA)–induced immunosuppression may serve as a novel approach in pharmacokinetics (PK)/pharmacodynamics (PD)–guided therapy. The authors prospectively studied MPA pharmacokinetics and IMPDH inhibition in 28 pediatric de novo kidney transplant recipients. Pretransplant IMPDH activity and full PK/PD profiles were obtained at 3 different occasions: 1 to 3 days, 4 to 9 days, and approximately 6 months after transplant. Large intra- and interpatient variability was noted in MPA pharmacokinetics and exposure and IMPDH inhibition. MPA exposure (AUC0-12 h) was low early posttransplant and increased over time and stabilized at months 3 to 6. Mean pretransplant IMPDH activity (6.4 ± 4.6 nmol/h/mg protein) was lower than previously reported in adults. In most of the patients, IMPDH enzyme activity decreased with increasing MPA plasma concentration, with maximum inhibition coinciding with maximum MPA concentration. The overall relationship between MPA concentration and IMPDH activity was described by a direct inhibitory Emax model (EC50 = 0.97 mg/L). This study suggests the importance of early PK/PD monitoring to improve drug exposure. Because IMPDH inhibition is well correlated to MPA concentration, pre-transplant IMPDH activity may serve as an early marker to guide the initial level of MPA exposure required in a pediatric population.
Cancer stage at diagnosis is the most important prognostic factor for survival. We conducted a nationwide, population-based cohort study to investigate cancer stage distribution in immigrants compared to the host population of Norway. All patients recorded in the Cancer Registry of Norway in 1990-2014 were included (17,709 immigrants and 431,936 Norwegians). Individual level sociodemographic data was obtained from Statistics Norway. Ordered logistic regression was used to estimate if immigrants were diagnosed with cancer at a more advanced stage than Norwegians. Seven cancer sites were analyzed (breast, cervix, colorectal, liver, lung and trachea, prostate and stomach). With exception of breast cancer, we did not observe a clear pattern of more advanced cancer stage distribution in immigrants compared to Norwegians. Odds ratios and corresponding 95% confidence intervals for being diagnosed with a more advanced stage of breast cancer for non-Western immigrant groups compared to Norwegians were: Eastern Europe: 1.41 (1.20-1.65), Middle East: 1.58 (1.19-2.10), sub-Saharan Africa: 1.44 (0.99-2.08), South Asia: 1.40 (1.07-1.83) and East Asia: 0.90 (0.72-1.13). Sub-analyses showed that late detection of breast cancer in young non-Western immigrants might be of particular concern. Young (<50 years) non-Western immigrants had an odds ratio of 1.40 (1.21-1.62) for more advanced stage breast cancer compared to young Norwegians.
Cancer survival is an important indicator for quality of cancer care. We sought to determine if there are differences in cancer survival between immigrants and the host population in Norway. We performed a nationwide registry-based study comprising subjects diagnosed with cancer between 1990 and 2014, and followed until the end of 2016. Survival was estimated for 13 cancer sites with cause-specific survival. Adjustments were made for common confounders (age, sex, year of diagnosis and place of residence) and defined mediators (stage at diagnosis, comorbidity and socioeconomic factors). A total of 500,255 subjects were available for analysis, of which 11,252 were Western and 8,701 non-Western immigrants. We did not find differences in cancer survival between Western immigrants and Norwegians, while non-Western immigrants, with some exceptions, had similar or better survival. Better lung cancer survival in non-Western immigrants than Norwegians was notable (hazard ratio (95% confidence interval): 0.78 (0.71-0.85)), and not explained by defined mediators. Immigrants from Eastern Europe and Balkan with melanoma (hazard ratio: 1.54 (1.12-2.12)) and prostate cancer (hazard ratio: 1.34 (1.08-1.67)), and possibly from sub-Saharan Africa with breast cancer (hazard ratio: 1.41 (0.94-2.12)) had worse survival than Norwegians. The results suggest that immigrants in Norway have good cancer survival relative to the host population. Poor survival in immigrants from Eastern Europe and Balkan with melanoma and prostate cancer, and sub-Saharan Africa with breast cancer might be a concern.
Background: There are concerns about timely access to appropriate cancer treatment for the growing immigrant population in Norway. This study aims to compare waiting times between cancer diagnosis and start of cancer treatment, as well as treatment patterns between immigrants in Norway and the host population. Material and methods: We performed a nationwide, registry-based study with individual-level data, including 213,320 Norwegians and 8324 immigrants diagnosed with breast, colorectal, lung or prostate cancer in 1990-2014. Differences in time from diagnosis to treatment and in treatment patterns were described for the selected cancer sites. The Cox and logistic regressions were used to adjust for patient and tumour characteristics. Results: After adjustment for covariates, hazard ratios for time from diagnosis to treatment for non-Western immigrants compared to Norwegians were 0.88 (95% confidence interval (CI): 0.82-0.95) for breast cancer and 0.84 (95% CI: 0.75-0.95) for lung cancer, indicating longer waiting times. Treatment patterns in the four major cancer sites were similar among immigrants and the Norwegian host population, except for breast cancer, where women from East and South Asia received less breast-conserving surgery than the Norwegian host population (adjusted odds ratios 0.65 (95% CI: 0.46-0.93) for East Asians and 0.75 (95% CI: 0.50-1.13) for South Asians). Conclusions: The present study reports delayed treatment for lung and breast cancer among immigrants from non-Western countries in Norway. Systematic differences in cancer treatment were not detected. However, less breast-conserving surgery among breast cancer patients from Asia compared to Norwegians was observed.
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