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Simple Summary: There are inequalities in cancer survival between patients with or without comorbidities. The healthcare pathway (i.e., diagnostic route) of a patient is thought to explain some of these inequalities. We explore how much of the effect of comorbidity on survival of patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) is explained by the diagnostic route (i.e., emergency diagnosis). We used mediation analysis to separate the effect of comorbidity on survival from its effect through diagnostic route. We found that, for DLBCL and FL, emergency diagnosis accounted for 24% and 16% of the inequalities in survival between comorbidity groups within 12 months since cancer diagnosis. This proportion reduced over time and was small after 5 years of follow up. Comorbidities can complicate the diagnosis and management of patients with DLBCL or FL. Our results show that greater research is needed to ensure patients with comorbidities have a timely diagnosis and will help to reduce the inequalities in cancer survival. Background: Socioeconomic inequalities in survival from non-Hodgkin lymphoma persist. Comorbidities are more prevalent amongst those in more deprived areas and are associated with diagnostic delay (emergency diagnostic route), which is also associated with poorer survival probability. We aimed to describe the effect of comorbidity on the probability of death mediated by diagnostic route (emergency vs. elective route) amongst patients with diffuse large B-cell (DLBCL) or follicular lymphoma (FL). Methods: We linked the English population-based cancer registry and hospital admission records (2005–2013) of patients aged 45–99 years. We decomposed the effect of comorbidity on survival into an indirect effect acting through diagnostic route and a direct effect not mediated by diagnostic route. Furthermore, we estimated the proportion of the comorbidity effect on survival mediated by diagnostic route. Results: For both DLBCL (n = 27,379) and FL (n = 14,043), those with any comorbidity, or living in more deprived areas, were more likely to experience diagnostic delay and poorer survival. The indirect effect of comorbidity on mortality through diagnostic route was highest at 12 months since diagnosis (DLBCL: Odds Ratio 1.10 [95% CI 1.07–1.13], FL: OR 1.09 [95% CI 1.04–1.14]). Within the first 12 months since diagnosis, emergency diagnostic route accounted for 24% (95% CI 17.5–29.5) and 16% (95% CI 6.0–25.6) of the comorbidity effect on mortality, for DLBCL and FL, respectively. Conclusion: Efforts to reduce diagnostic delay (emergency diagnosis) amongst patients with comorbidity would reduce inequalities in DLBCL and FL survival by 24% and 16%, respectively. Further public health programs and interventions are needed to reduce diagnostic delay amongst lymphoma patients with comorbidities. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency during pregnancy has been associated with increased risk of complications and adverse perinatal outcomes. We evaluated seasonal variation of 25-hydroxyvitamin D [25(OH)D] among pregnant women, focusing on patterns and determinants of variation.Methods: Data came from three cohort studies in the US that included 2583 non-Hispanic Black and White women having prenatal 25(OH)D concentrations determined. Fourier time series and generalised linear models were used to estimate the magnitude of 25(OH)D seasonality. We modelled seasonal variability using a stationary cosinor model to estimate the phase shift, peak-trough difference, and annual mean of 25(OH)D.Results: We observed a peak for 25(OH)D in summer, a nadir in winter, and a phase of 8 months, which resulted from fluctuations in 25(OH)D3 rather than 25(OH)D2. After adjustment for covariates, the annual mean concentrations and estimated peak-trough difference of 25(OH)D among Black women were 19.8 ng/mL [95% confidence interval (CI) 18.9, 20.5] and 5.8 ng/mL [95% CI 4.7, 6.7], and for non-Hispanic White women were 33.0 ng/mL [95% CI 32.6, 33.4] and 7.4 ng/mL [95% CI 6.0, 8.9].Conclusions: Non-Hispanic Black women had lower average 25(OH)D concentrations throughout the year and smaller seasonal variation levels than non-Hispanic White women. This study's confirmation of 25(OH)D seasonality over a calendar year has the potential to enhance public health interventions targeted to improve maternal and perinatal outcomes. [ABSTRACT FROM AUTHOR]

Background: Innovative models of care are required to cope with the ever-increasing number of patients on antiretroviral therapy in the most affected countries. This study, in Khayelitsha, South Africa, evaluates the effectiveness of a group-based model of care run predominantly by non-clinical staff in retaining patients in care and maintaining adherence. Methods and Findings: Participation in “adherence clubs” was offered to adults who had been on ART for at least 18 months, had a current CD4 count >200 cells/ml and were virologically suppressed. Embedded in an ongoing cohort study, we compared loss to care and virologic rebound in patients receiving the intervention with patients attending routine nurse-led care from November 2007 to February 2011. We used inverse probability weighting to estimate the intention-to-treat effect of adherence club participation, adjusted for measured baseline and time-varying confounders. The principal outcome was the combination of death or loss to follow-up. The secondary outcome was virologic rebound in patients who were virologically suppressed at study entry. Of 2829 patients on ART for >18 months with a CD4 count above 200 cells/µl, 502 accepted club participation. At the end of the study, 97% of club patients remained in care compared with 85% of other patients. In adjusted analyses club participation reduced loss-to-care by 57% (hazard ratio [HR] 0.43, 95% CI = 0.21–0.91) and virologic rebound in patients who were initially suppressed by 67% (HR 0.33, 95% CI = 0.16–0.67). Discussion: Patient adherence groups were found to be an effective model for improving retention and documented virologic suppression for stable patients in long term ART care. Out-of-clinic group-based models facilitated by non-clinical staff are a promising approach to assist in the long-term management of people on ART in high burden low or middle-income settings. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite political efforts across the world and Europe, social inequalities in cancer incidence are persistent. We studied the association between socioeconomic status (SES) and cancer incidence in nine Spanish provinces. Lower SES was associated with an increased risk of lung cancer among males. Higher SES was associated with an increased risk of breast cancer among females in Spain. Understanding the reasons behind the association between cancer incidence and SES could help develop appropriate public health programs to promote health and reduce socioeconomic inequalities in cancer incidence in Spain. Socioeconomic inequalities in cancer incidence are not well documented in southern Europe. We aim to study the association between socioeconomic status (SES) and colorectal, lung, and breast cancer incidence in Spain. We conducted a multilevel study using data from Spanish population-based cancer registries, including incident cases diagnosed for the period 2010–2013 in nine Spanish provinces. We used Poisson mixed-effects models, including the census tract as a random intercept, to derive cancer incidence rate ratios by SES, adjusted for age and calendar year. Male adults with the lowest SES, compared to those with the highest SES, showed weak evidence of being at increased risk of lung cancer (risk ratio (RR): 1.18, 95% CI: 0.94–1.46) but showed moderate evidence of being at reduced risk of colorectal cancer (RR: 0.84, 95% CI: 0.74–0.97). Female adults with the lowest SES, compared to those with the highest SES, showed strong evidence of lower breast cancer incidence with 24% decreased risk (RR: 0.76, 95% CI: 0.68–0.85). Among females, we did not find evidence of an association between SES and lung or colorectal cancer. The associations found between SES and cancer incidence in Spain are consistent with those obtained in other European countries. [ABSTRACT FROM AUTHOR]

Simple Summary: There is limited evidence regarding the influence of socioeconomic factors on COVID-19 transmission, severity and outcomes in the overall population. Furthermore, there is an urgent need to identify and explore the most important socioeconomic risk factors associated with the COVID-19 disease among incident cancer patients, one of the most vulnerable groups of the population. Findings from this study provide invaluable evidence needed for risk classification and stratification among incident cancer patients, based on the information from the first pandemic wave in the UK. We identified the clinical and socio-demographic profile of cancer patients at increased risk of COVID-19 infection. The results from the study added knowledge on impact of the pandemic on the most vulnerable cancer patients in the UK, and can shed light on possible treatment and prevention strategies for COVID-19, including future vaccination prioritisation policy. We explored the role of socioeconomic inequalities in COVID-19 incidence among cancer patients during the first wave of the pandemic. We conducted a case-control study within the UK Biobank cohort linked to the COVID-19 tests results available from 16 March 2020 until 23 August 2020. The main exposure variable was socioeconomic status, assessed using the Townsend Deprivation Index. Among 18,917 participants with an incident malignancy in the UK Biobank cohort, 89 tested positive for COVID-19. The overall COVID-19 incidence was 4.7 cases per 1000 incident cancer patients (95%CI 3.8–5.8). Compared with the least deprived cancer patients, those living in the most deprived areas had an almost three times higher risk of testing positive (RR 2.6, 95%CI 1.1–5.8). Other independent risk factors were ethnic minority background, obesity, unemployment, smoking, and being diagnosed with a haematological cancer for less than five years. A consistent pattern of socioeconomic inequalities in COVID-19 among incident cancer patients in the UK highlights the need to prioritise the cancer patients living in the most deprived areas in vaccination planning. This socio-demographic profiling of vulnerable cancer patients at increased risk of infection can inform prevention strategies and policy improvements for the coming pandemic waves. [ABSTRACT FROM AUTHOR]

The targeted maximum likelihood estimation (TMLE) statistical data analysis framework integrates machine learning, statistical theory, and statistical inference to provide a least biased, efficient, and robust strategy for estimation and inference of a variety of statistical and causal parameters. We describe and evaluate the epidemiological applications that have benefited from recent methodological developments. We conducted a systematic literature review in PubMed for articles that applied any form of TMLE in observational studies. We summarized the epidemiological discipline, geographical location, expertize of the authors, and TMLE methods over time. We used the Roadmap of Targeted Learning and Causal Inference to extract key methodological aspects of the publications. We showcase the contributions to the literature of these TMLE results. Of the 89 publications included, 33% originated from the University of California at Berkeley, where the framework was first developed by Professor Mark van der Laan. By 2022, 59% of the publications originated from outside the United States and explored up to seven different epidemiological disciplines in 2021–2022. Double-robustness, bias reduction, and model misspecification were the main motivations that drew researchers toward the TMLE framework. Through time, a wide variety of methodological, tutorial, and software-specific articles were cited, owing to the constant growth of methodological developments around TMLE. There is a clear dissemination trend of the TMLE framework to various epidemiological disciplines and to increasing numbers of geographical areas. The availability of R packages, publication of tutorial papers, and involvement of methodological experts in applied publications have contributed to an exponential increase in the number of studies that understood the benefits and adoption of TMLE. [ABSTRACT FROM AUTHOR]