When estimating the average effect of a binary treatment (or exposure) on an outcome, methods that incorporate propensity scores, the G‐formula, or targeted maximum likelihood estimation (TMLE) are ...preferred over naïve regression approaches, which are biased under misspecification of a parametric outcome model. In contrast propensity score methods require the correct specification of an exposure model. Double‐robust methods only require correct specification of either the outcome or the exposure model. Targeted maximum likelihood estimation is a semiparametric double‐robust method that improves the chances of correct model specification by allowing for flexible estimation using (nonparametric) machine‐learning methods. It therefore requires weaker assumptions than its competitors. We provide a step‐by‐step guided implementation of TMLE and illustrate it in a realistic scenario based on cancer epidemiology where assumptions about correct model specification and positivity (ie, when a study participant had 0 probability of receiving the treatment) are nearly violated. This article provides a concise and reproducible educational introduction to TMLE for a binary outcome and exposure. The reader should gain sufficient understanding of TMLE from this introductory tutorial to be able to apply the method in practice. Extensive R‐code is provided in easy‐to‐read boxes throughout the article for replicability. Stata users will find a testing implementation of TMLE and additional material in the Appendix S1 and at the following GitHub repository: https://github.com/migariane/SIM‐TMLE‐tutorial
Individual and tumour factors only explain part of observed inequalities in colorectal cancer survival in England. This study aims to investigate inequalities in treatment in patients with colorectal ...cancer.
All patients diagnosed with colorectal cancer in England between 2012 and 2016 were followed up from the date of diagnosis (state 1), to treatment (state 2), death (state 3) or censored at 1 year after the diagnosis. A multistate approach with flexible parametric model was used to investigate the effect of income deprivation on the probability of remaining alive and treated in colorectal cancer.
Compared to the least deprived quintile, the most deprived with stage I-IV colorectal cancer had a lower probability of being alive and treated at all the time during follow-up, and a higher probability of being untreated and of dying. The probability differences (most vs. least deprived) of being alive and treated at 6 months ranged between -2.4% (95% CI: -4.3, -1.1) and -7.4% (-9.4, -5.3) for colon; between -2.0% (-3.5, -0.4) and -6.2% (-8.9, -3.5) for rectal cancer.
Persistent inequalities in treatment were observed in patients with colorectal cancer at every stage, due to delayed access to treatment and premature death.
Patients with comorbidities do not receive optimal treatment for their cancer, leading to lower cancer survival. Information on individual comorbidities is not straightforward to derive from ...population-based administrative health datasets. We described the development of a reproducible algorithm to extract the individual Charlson index comorbidities from such data. We illustrated the algorithm with 1,789 laryngeal cancer patients diagnosed in England in 2013. We aimed to clearly set out and advocate the time-related assumptions specified in the algorithm by providing empirical evidence for them.
Comorbidities were assessed from hospital records in the ten years preceding cancer diagnosis and internal reliability of the hospital records was checked. Data were right-truncated 6 or 12 months prior to cancer diagnosis to avoid inclusion of potentially cancer-related comorbidities. We tested for collider bias using Cox regression.
Our administrative data showed weak to moderate internal reliability to identify comorbidities (ICC ranging between 0.1 and 0.6) but a notably high external validity (86.3%). We showed a reverse protective effect of non-cancer related Chronic Obstructive Pulmonary Disease (COPD) when the effect is split into cancer and non-cancer related COPD (Age-adjusted HR: 0.95, 95% CI:0.7-1.28 for non-cancer related comorbidities). Furthermore, we showed that a window of 6 years before diagnosis is an optimal period for the assessment of comorbidities.
To formulate a robust approach for assessing common comorbidities, it is important that assumptions made are explicitly stated and empirically proven. We provide a transparent and consistent approach useful to researchers looking to assess comorbidities for cancer patients using administrative health data.
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.
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).
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.
The presence of comorbidity affects the care of cancer patients, many of whom are living with multiple comorbidities. The prevalence of cancer comorbidity, beyond summary metrics, is not well known. ...This study aims to estimate the prevalence of comorbid conditions among cancer patients in England, and describe the association between cancer comorbidity and socio-economic position, using population-based electronic health records.
We linked England cancer registry records of patients diagnosed with cancer of the colon, rectum, lung or Hodgkin lymphoma between 2009 and 2013, with hospital admissions records. A comorbidity was any one of fourteen specific conditions, diagnosed during hospital admission up to 6 years prior to cancer diagnosis. We calculated the crude and age-sex adjusted prevalence of each condition, the frequency of multiple comorbidity combinations, and used logistic regression and multinomial logistic regression to estimate the adjusted odds of having each condition and the probability of having each condition as a single or one of multiple comorbidities, respectively, by cancer type.
Comorbidity was most prevalent in patients with lung cancer and least prevalent in Hodgkin lymphoma patients. Up to two-thirds of patients within each of the four cancer patient cohorts we studied had at least one comorbidity, and around half of the comorbid patients had multiple comorbidities. Our study highlighted common comorbid conditions among the cancer patient cohorts. In all four cohorts, the odds of having a comorbidity and the probability of multiple comorbidity were consistently highest in the most deprived cancer patients.
Cancer healthcare guidelines may need to consider prominent comorbid conditions, particularly to benefit the prognosis of the most deprived patients who carry the greater burden of comorbidity. Insight into patterns of cancer comorbidity may inform further research into the influence of specific comorbidities on socio-economic inequalities in receipt of cancer treatment and in short-term mortality.
Primary aldosteronism is recognized as a severe form of renin-independent aldosteronism that results in excessive mineralocorticoid receptor (MR) activation.
To investigate whether a spectrum of ...subclinical renin-independent aldosteronism that increases risk for hypertension exists among normotensive persons.
Cohort study.
National community-based study.
850 untreated normotensive participants in MESA (Multi-Ethnic Study of Atherosclerosis) with measurements of serum aldosterone and plasma renin activity (PRA).
Longitudinal analyses investigated whether aldosterone concentrations, in the context of physiologic PRA phenotypes (suppressed, ≤0.50 µg/L per hour; indeterminate, 0.51 to 0.99 µg/L per hour; unsuppressed, ≥1.0 µg/L per hour), were associated with incident hypertension (defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or initiation of antihypertensive medications). Cross-sectional analyses investigated associations between aldosterone and MR activity, assessed via serum potassium and urinary fractional excretion of potassium.
A suppressed renin phenotype was associated with a higher rate of incident hypertension than other PRA phenotypes (incidence rates per 1000 person-years of follow-up: suppressed renin phenotype, 85.4 events 95% CI, 73.4 to 99.3 events; indeterminate renin phenotype, 53.3 events CI, 42.8 to 66.4 events; unsuppressed renin phenotype, 54.5 events CI, 41.8 to 71.0 events). With renin suppression, higher aldosterone concentrations were independently associated with an increased risk for incident hypertension, whereas no association between aldosterone and hypertension was seen when renin was not suppressed. Higher aldosterone concentrations were associated with lower serum potassium and higher urinary excretion of potassium, but only when renin was suppressed.
Sodium and potassium were measured several years before renin and aldosterone.
Suppression of renin and higher aldosterone concentrations in the context of this renin suppression are associated with an increased risk for hypertension and possibly also with increased MR activity. These findings suggest a clinically relevant spectrum of subclinical primary aldosteronism (renin-independent aldosteronism) in normotension.
National Institutes of Health.
Abstract
The influence of socioeconomic status (SES) on access to standard chemotherapy and/or monoclonal antibody therapy, and associated secular trends, relative survival, and excess mortality, ...among diffuse large B-cell lymphoma (DLBCL) patients is not clear. We conducted a Hong Kong population-based cohort study and identified adult patients with histologically diagnosed DLBCL between 2000 and 2018. We examined the association of SES levels with the odds and the secular trends of receipt of chemotherapy and/or rituximab. Additionally, we estimated the long-term relative survival by SES utilizing Hong Kong life tables. Among 4017 patients with DLBCL, 2363 (58.8%) patients received both chemotherapy and rituximab and 740 (18.4%) patients received chemotherapy alone, while 1612 (40.1%) and 914 (22.8%) patients received no rituximab or chemotherapy, respectively. On multivariable analysis, low SES was associated with lesser use of chemotherapy (odd ratio OR 0.44; 95% CI 0.34–0.57) and rituximab (OR 0.41; 95% CI 0.32–0.52). The socioeconomic disparity for either treatment showed no secular trend of change. Additionally, patients with low SES showed increased excess mortality, with a hazard ratio of 2.34 (95% CI 1.67–3.28). Improving survival outcomes for patients with DLBCL requires provision of best available medical care and securing access to treatment regardless of patients’ SES.
Abstract Objective To evaluate the independent and combined associations of maternal self-reported poor sleep quality and antepartum depression with suicidal ideation during the third trimester ...Methods A cross-sectional study was conducted among 1,298 pregnant women (between 24 and 28 gestational weeks) attending prenatal clinics in Lima, Peru. Antepartum depression and suicidal ideation were assessed using the Patient Health Questionnaire-9 (PHQ-9). The Pittsburgh Sleep Quality Index (PSQI) questionnaire was used to assess sleep quality. Multivariate logistical regression procedures were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) after adjusting for putative confounders. Results Approximately, 17% of women were classified as having poor sleep quality (defined using the recommended criteria of PSQI global score of >5 vs. ≤5). Further, the prevalence of antepartum depression and suicidal ideation were 10.3% and 8.5%, respectively in this cohort. After adjusting for confounders including depression, poor sleep quality was associated with a 2.81-fold increased odds of suicidal ideation (OR=2.81; 95% CI 1.78–4.45). When assessed as a continuous variable, each 1-unit increase in the global PSQI score resulted in a 28% increase in odds for suicidal ideation, even after adjusting for depression (OR=1.28; 95% CI 1.15–1.41). The odds of suicidal ideation was particularly high among depressed women with poor sleep quality (OR=13.56 95% CI 7.53–24.41) as compared with women without either risk factor. Limitations This cross-sectional study utilized self-reported data. Causality cannot be inferred, and results may not be fully generalizable. Conclusion Poor sleep quality, even after adjusting for depression, is associated with antepartum suicidal ideation. Our findings support the need to explore sleep-focused interventions for pregnant women.
Survival data analysis results are usually communicated through the overall survival probability. Alternative measures provide additional insights and may help in communicating the results to a wider ...audience. We describe these alternative measures in two data settings, the overall survival setting and the relative survival setting, the latter corresponding to the particular competing risk setting in which the cause of death is unavailable or unreliable. In the overall survival setting, we describe the overall survival probability, the conditional survival probability and the restricted mean survival time (restricted to a prespecified time window). In the relative survival setting, we describe the net survival probability, the conditional net survival probability, the restricted mean net survival time, the crude probability of death due to each cause and the number of life years lost due to each cause over a prespecified time window. These measures describe survival data either on a probability scale or on a timescale. The clinical or population health purpose of each measure is detailed, and their advantages and drawbacks are discussed. We then illustrate their use analyzing England population-based registry data of men 15-80 years old diagnosed with colon cancer in 2001-2003, aiming to describe the deprivation disparities in survival. We believe that both the provision of a detailed example of the interpretation of each measure and the software implementation will help in generalizing their use.
Diagnostic delay is associated with lower chances of cancer survival. Underlying comorbidities are known to affect the timely diagnosis of cancer. Diffuse large B-cell (DLBCL) and follicular ...lymphomas (FL) are primarily diagnosed amongst older patients, who are more likely to have comorbidities. Characteristics of clinical commissioning groups (CCG) are also known to impact diagnostic delay. We assess the association between comorbidities and diagnostic delay amongst patients with DLBCL or FL in England during 2005-2013.
Multivariable generalised linear mixed-effect models were used to assess the main association. Empirical Bayes estimates of the random effects were used to explore between-cluster variation. The latent normal joint modelling multiple imputation approach was used to account for partially observed variables.
We included 30,078 and 15,551 patients diagnosed with DLBCL or FL, respectively. Amongst patients from the same CCG, having multimorbidity was strongly associated with the emergency route to diagnosis (DLBCL: odds ratio 1.56, CI 1.40-1.73; FL: odds ratio 1.80, CI 1.45-2.23). Amongst DLBCL patients, the diagnostic delay was possibly correlated with CCGs that had higher population densities.
Underlying comorbidity is associated with diagnostic delay amongst patients with DLBCL or FL. Results suggest a possible correlation between CCGs with higher population densities and diagnostic delay of aggressive lymphomas.
PDF
