The Charlson comorbidity index in registry-based research : which version to use?

Background: Comorbidities may have an important impact on survival, and comorbidity scores are often implemented in studies assessing prognosis. The Charlson Comorbidity index is most widely used, yet several adaptations have been published, all using slightly different conversions of the International Classification of Diseases (ICD) coding. Objective: To evaluate which coding should be used to assess and quantify comorbidity for the Charlson Comorbidity Index for registry-based research, in particular if older ICD versions will be used. Methods: A systematic literature search was used to identify adaptations and modifications of the ICD-coding of the Charlson Comorbidity Index for general purpose in adults, published in English. Back-translation to ICD version 8 and version 9 was conducted by means of the ICD-code converter of Statistics Sweden. Results: In total, 16 studies were identified reporting ICD-adaptations of the Charlson Comorbidity Index. The Royal College of Surgeons in them United Kingdom combined 5 versions into, an adapted and updated version which appeared appropriate for research purposes. Their ICD-10 codes were back-translated into ICD-9 and ICD-8 according to their Proposed adaptations, and verified with previous versions of the Charlson Comorbidity Index. Conclusion: Many versions of the Charlson Comorbidity Index are used in parallel, so clear reporting of the version, exact ICD-coding and weighting is necessary to obtain transparency and reproducibility in research. Yet, the version of the Royal College of Surgeons is up-to-date and easy-to-use, and therefore an acceptable co-morbidity score to be used in registry-based research especially for surgical patients

Weekday of oesophageal cancer surgery in relation to early postoperative outcomes in a nationwide Swedish cohort study

Objectives: Later weekday of surgery for oesophageal cancer seems to increases 5-year mortality, but the mechanisms are unclear. We hypothesised that early postoperative reoperations and mortality might explain this association, since reoperation after oesophagectomy decreases long-term prognosis and later weekday of elective surgery increases 30-day mortality. Design: This was a population-based cohort study during the study period 1987-2014. Setting: All Swedish hospitals conducting elective surgery for oesophageal cancer in Sweden. Participants: Included were 1,748 patients, representing almost all (98%) patients who underwent elective surgery for oesophageal cancer in Sweden during 1987-2010, with follow-up until 2014. Primary and secondary outcome measures: The risk of reoperation or mortality within 30 days of oesophageal cancer surgery was assessed in relation to weekday of surgery by calculating odds ratios (ORs) with 95% confidence intervals (CIs) using multivariable logistic regression. ORs were adjusted for age, co-morbidity, tumour stage, histology, neoadjuvant therapy, and surgeon volume. Results: Surgery Wednesday-Friday did not increase the risk of reoperation or mortality compared to surgery Monday-Tuesday (OR=0.99, 95% CI 0.75-1.31). A decreased point estimate of reoperation (OR=0.88, 95% CI 0.64-1.21) was counteracted by an increased point estimate of mortality (OR=1.28, 95% CI 0.83-1.99). ORs did not increase from Monday to Friday when each weekday was analysed separately. There was no association between weekday of surgery and reoperation specifically for anastomotic leak, laparotomy, or wound infection. Stratification for surgeon volume did not reveal any clear associations between weekday of surgery and risk of 30-day reoperation or mortality. Conclusions: Weekday of oesophageal cancer surgery does not seem to influence the risk of reoperation or mortality within 30 days of surgery, and thus cannot explain the association between weekday of surgery and long-term prognosis.The Swedish Research CouncilThe Swedish Cancer SocietyAccepte

The male predominance in esophageal adenocarcinoma

The incidence of esophageal adenocarcinoma (EAC) has increased rapidly during the past four decades in many Western populations, including North America and Europe. The established etiological factors for EAC include gastro-esophageal reflux and obesity, Helicobacter pylori infection, tobacco smoking, and consumption of fruit and vegetables. There is a marked male predominance of EAC with a male-to-female ratio in incidence of up to 9-to-1. This review evaluates the available literature on the reasons for the male predominance, particularly an update on epidemiologic evidence from human studies during the past decade. The striking sex difference does not seem to be explained by established risk factors, given that the prevalence of the etiological factors and the strengths of associations between these factors and EAC risk are similar between the sexes. Sex hormonal factors may play a role in the development of EAC; estrogenic exposures may prevent such development, while androgens might increase the risk of EAC. However, continuing research efforts are still in need to fully understand the reasons for the male predominance of EAC.Swedish Research CouncilSwedish Cancer SocietyAccepte

A global assessment of the male predominance in esophageal adenocarcinoma

Background: Esophageal adenocarcinoma (EAC) is characterized by a male predominance. However, variations in the sex difference across populations and over time have not previously been thoroughly investigated. Results: The male-to-female ratio in EAC incidence varied greatly across continents, ranging from 1.03 in Africa to 7.64 in Northern America during 2003– 2007. The ratio was high in Europe (6.04) and Oceania (6.24), and lower in Asia (4.37) and Latin America and the Caribbean (3.94). The sex ratio remained relatively stable over time in most populations. In absolute terms, the sex difference in EAC incidence increased over time in populations of higher incidence, while it remained stable or slightly decreased in low-incidence populations. Materials and Methods: We used data from the Cancer Incidence in Five Continents series to compute sex-specific age-standardized rates of EAC by population. The sex difference in incidence was evaluated on both absolute and relative scales, measured by the absolute difference and ratio between sexes, respectively. Conclusions: This first global assessment of the sex ratio in EAC shows that the male predominance is particularly strong in developed countries. The underlying reasons remain to be identified, but the emerging EAC burden in men merits consideration for targeted prevention and early detection.Swedish Research Council (SIMSAM)Swedish Cancer SocietyPublishe

A model for predicting individuals' absolute risk of esophageal adenocarcinoma : moving toward tailored screening and prevention

Esophageal adenocarcinoma (EAC) is characterized by rapidly increasing incidence and poor prognosis, stressing the need for preventive and early detection strategies. We used data from a nationwide population-based case-control study, which included 189 incident cases of EAC and 820 age- and sex-matched control participants, from 1995 through 1997 in Sweden. We developed risk prediction models based on unconditional logistic regression. Candidate predictors included established and readily identifiable risk factors for EAC. The performance of model was assessed by the area under receiver operating characteristic curve (AUC) with cross-validation. The final model could explain 94% of all case patients with EAC (94% population attributable risk) and included terms for gastro-esophageal reflux symptoms or use of antireflux medication, body mass index (BMI), tobacco smoking, duration of living with a partner, previous diagnoses of esophagitis and diaphragmatic hernia and previous surgery for esophagitis, diaphragmatic hernia or severe reflux or gastric or duodenal ulcer. The AUC was 0.84 (95% confidence interval [CI] 0.81-0.87) and slightly lower after cross-validation. A simpler model, based only on reflux symptoms or use of antireflux medication, BMI and tobacco smoking could explain 91% of the case patients with EAC and had an AUC of 0.82 (95% CI 0.78-0.85). These EAC prediction models showed good discriminative accuracy, but need to be validated in other populations. These models have the potential for future use in identifying individuals with high absolute risk of EAC in the population, who may be considered for endoscopic screening and targeted prevention.Swedish Research Council, D0547801Swedish Cancer Society, 14 0322Accepte

Using the Lorenz curve to assess the feasibility of targeted screening for esophageal adenocarcinoma

Swedish Research CouncilSwedish Cancer SocietyAccepte

Weekday of esophageal cancer surgery and its relation to prognosis

Objective: To assess whether weekday of surgery influences long-term survival in esophageal cancer. Summary Background Data: Increased 30-day mortality rates have been reported in patients undergoing elective surgery later compared to earlier in the week Methods: This population-based cohort study included 98% of all esophageal cancer patients who underwent elective surgery in Sweden in 1987-2010, with follow-up until 2014. The association between weekday of surgery and 5-year all-cause and disease-specific mortality was analyzed using a multivariable Cox proportional hazards model, providing hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for age, co-morbidity, tumor stage, histology, neoadjuvant therapy, and surgeon volume. Results: Among 1,748 included patients, surgery conducted Wednesday-Friday entailed 13% increased all-cause 5-year mortality compared to surgery Monday-Tuesday (HR=1.13, 95% CI 1.01-1.26). The corresponding association was strong for early tumor stages (0-I) (HR=1.59, 95% CI 1.17-2.16), moderate for intermediate tumor stage (II) (HR=1.28, 95% CI 1.07-1.53), and absent in advanced tumor stages (III-IV) (HR=0.93, 95%CI 0.79-1.09). The increase in 5-year mortality for each later weekday (discrete variable) was 7% for all tumor stages (HR=1.07, 95% CI 1.02-1.12), 24% for early tumor stages (HR=1.24, 95% CI 1.09-1.41), 13% for intermediate stage (HR=1.13, 95% CI 1.05-1.22), while no increase was found for advanced stages (HR=0.98, 95% CI 0.92-1.05). The disease-specific 5-year mortality was similar to the all-cause mortality. Conclusions: The increased 5-year mortality of potentially curable esophageal cancer following surgery later in the week suggests that this surgery is better performed earlier in the week.Swedish Research CouncilSwedish Cancer SocietyAccepte

Prognosis following cancer surgery during holiday periods

Swedish Research Council for Health, Working Life and Welfare (Forte)Accepte

Weekday of cancer surgery in relation to prognosis

BACKGROUND: Later weekday of surgery seems to affect the prognosis adversely in oesophageal cancer, whereas any such influence on other cancer sites is unknown. This study aimed to test whether weekday of surgery influenced prognosis following commonly performed cancer operations. METHODS: This nationwide Swedish population-based cohort study from 1997 to 2014 analysed weekday of elective surgery for ten major cancers in relation to disease-specific and all-cause mortality. Cox regression provided hazard ratios with 95 per cent confidence intervals, adjusted for the co-variables age, sex, co-morbidity, hospital volume, calendar year and tumour stage. RESULTS: A total of 228 927 patients were included. Later weekday of surgery (Thursdays and, even more so, Fridays) was associated with increased mortality rates for gastrointestinal cancers. Adjusted hazard ratios for disease-specific mortality, comparing surgery on Friday with that on Monday, were 1·57 (95 per cent c.i. 1·31 to 1·88) for oesophagogastric cancer, 1·49 (1·17 to 1·88) for liver/pancreatic/biliary cancer and 1·53 (1·44 to 1·63) for colorectal cancer. Excluding mortality during the initial 90 days of surgery made little difference to these findings, and all-cause mortality was similar to disease-specific mortality. The associations were similar in analyses stratified for co-variables. No consistent associations were found between weekday of surgery and prognosis for cancer of the head and neck, lung, thyroid, breast, kidney/bladder, prostate or ovary/uterus.the Swedish Research Councilthe Swedish Cancer SocietyKarolinska Institutet Distinguished Professor Award to Professor Jesper LagergrenAccepte

Maintenance therapy with proton pump inhibitors and risk of gastric cancer : a nationwide population-based cohort study in Sweden

Objective: Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs. Concerns have been raised about a potentially increased risk of gastric cancer following long-term use. Our aim is to assess the risk of gastric cancer associated with PPI use, taking into account underlying indications. Design: This is a population-based cohort study. Standardised incidence ratios (SIRs) and 95% CIs were calculated to compare the risk of gastric cancer among long-term PPI users with the corresponding background population, while taking confounding by indication into account. Setting: Population-based study in Sweden (2005-2012). Participants: This study included virtually all adults residing in Sweden exposed to maintenance therapy with PPIs. Exposure/Intervention: Maintenance use of PPIs, defined as at least 180 days during the study period. Maintenance use of histamine 2 receptor antagonist was evaluated for comparison reasons. Outcome measures: Gastric cancer (cardia and non-cardia), and subgroup analysis for gastric adenocarcinoma, as defined by the Swedish Cancer Registry. Results: Among 797 067 individuals on maintenance PPI therapy, the SIR of gastric cancer was over threefold increased (SIR=3.38, 95% CI 3.23 to 3.53). Increased SIRs were found in both sexes and all age groups, but were especially increased among PPI users younger than 40 years (SIR=22.76, 95% CI 15.94 to 31.52). Increased SIRs were found for each indication studied, including those without an association with gastric cancer, for example, gastro-oesophageal reflux (SIR=3.04, 95% CI 2.80 to 3.31), and those with a supposedly decreased risk, for example, aspirin users (SIR=1.93, 95% CI 1.70 to 2.18). The association was similar for cardia and non-cardia gastric cancer. Analyses restricted to adenocarcinoma showed similar results to those for all gastric cancers. Long-term users of histamine 2 receptor antagonists, which have the same indications as PPIs, were not at any increased risk. Conclusions: Long-term PPI use might be an independent risk factor for gastric cancer. This challenges broad maintenance PPI therapy, particularly if the indication is weak