Effects of neoadjuvant therapy on health-related quality of life for patients with gastroesophageal cancer.

BACKGROUND: Neoadjuvant therapy in combination with surgery increases survival in gastroesophageal cancer; however, little is known about its impact on health-related quality of life. This study compared the impact of neoadjuvant therapy with that of surgery alone on the health-related quality of life in patients treated for gastroesophageal cancer. METHODS: A single-centre cohort study with prospectively collected data from patients undergoing curative intended treatment for gastroesophageal cancer between 2013 and 2020 was performed. Health-related quality of life was assessed prior to surgery and patients stratified according to neoadjuvant therapy or surgery alone. The primary endpoint was self-assessed health-related quality of life, evaluated using validated cancer-specific questionnaires. A pre-specified multivariable model adjusted for age, ASA score, and clinical T- and N-stage was used. RESULTS: A total of 361 patients were included, of whom 239 (61%) were treated with neoadjuvant therapy. Patients treated with neoadjuvant therapy reported less difficulties with eating restrictions (-11.9, p = 0.005), pain (-10.9, p = 0.004), and insomnia (-12.6, p = 0.004) than patients treated with surgery alone. Patients with oesophageal cancer and neoadjuvant therapy reported less dysphagia (-16.6, p < 0.001), eating restrictions (-23.2, p < 0.001), and odynophagia (-18.0, p = 0.002) than those who underwent surgery alone. CONCLUSION: Neoadjuvant therapy was associated with a significant reduction in symptoms affecting malnutrition and improved health-related quality of life in patients with gastroesophageal cancer. These results indicates that more patients might be available for neoadjuvant therapy, despite the baseline burden of gastroesophageal cancer.

Nutritional jejunostomy in esophagectomy for cancer, a national register-based cohort study of associations with postoperative outcomes and survival.

PURPOSE: Insertion of a nutritional jejunostomy in conjunction with esophagectomy is performed with the intention to decrease the risk for postoperative malnutrition and improve recovery without adding significant catheter-related complications. However, previous research has shown no clear benefit and there is currently no consensus of practice. METHODS: All patients treated with esophagectomy due to cancer during the period 2006-2017 reported in the Swedish National Register for Esophageal and Gastric Cancer were included in this register-based cohort study from a national database. Patients were stratified into two groups: esophagectomy alone and esophagectomy with jejunostomy. RESULTS: A total of 847 patients (45.27%) had no jejunostomy inserted while 1024 patients (54.73%) were treated with jejunostomy. The groups were comparable, but some differences were seen in histological tumor type and tumor stage between the groups. No significant differences in length of hospital stay, postoperative surgical complications, Clavien-Dindo score, or 90-day mortality rate were seen. There was no evidence of increased risk for significant jejunostomy-related complications. Patients in the jejunostomy group with anastomotic leaks had a statistically significant lower risk for severe morbidity defined as Clavien-Dindo score ≥ IIIb (adjusted odds ratio 0.19, 95% CI: 0.04-0.94, P = 0.041) compared to patients with anastomotic leaks and no jejunostomy. CONCLUSION: A nutritional jejunostomy is a safe method for early postoperative enteral nutrition which might decrease the risk for severe outcomes in patients with anastomotic leaks. Nutritional jejunostomy should be considered for patients undergoing curative intended surgery for esophageal and gastro-esophageal junction cancer.

Sociodemographic changes in the population frequency of colonoscopy following the implementation of organised bowel cancer screening: An analysis of data from Swedish registers, 2006-2015.

OBJECTIVE: To assess sociodemographic changes in the population frequency of colonoscopy (PFC; number of colonoscopies per 1000 inhabitants per year) among people aged 50-74 in relation to the implementation of a regional colorectal cancer screening programme for people aged 60-69 in the Stockholm-Gotland region (RSG) in 2008. METHOD: The PFC was estimated by year (2006-2015), pre- and post-implementation of colorectal cancer screening programme (2006-2007 vs. 2014-2015), age, sex, residential region, immigrant status and educational level. The data were obtained from Swedish patient and population registers. RESULTS: The PFC largely increased during 2006-2015 in all six Swedish regions. The estimated increase in the pre- vs. post period PFC (ΔPFC) within the RSG was (i) greater for men than for women (5.8 vs. 4.5) and (ii) smaller for people aged 70-74 than for those aged 60-69 (5.5 vs. 9.0), while the corresponding ΔPFCs within each of the other regions were (i) not greater, or even smaller, for men and (ii) not smaller, or even larger, for elderly people aged 70-74. CONCLUSION: A regional implementation of an organised colorectal cancer screening programme did not lead to a higher PFC increase in the screening relevant age group 50-74 years. Nevertheless, changes in the PFC were more pronounced for men and less pronounced for people aged 70-74 than those invited to participate in the screening programme (60-69 years), as compared with the rest of Sweden (without organised colorectal cancer screening).

Decentralising atrial fibrillation screening to overcome socio-demographic inequalities in uptake in STROKESTOP II.

OBJECTIVE: In the first STROKESTOP atrial fibrillation screening study, participation was influenced by socio-demographic and geographic factors. To improve uptake in the second study, two screening sites were added, closer to low-income neighbourhoods which had very low participation in the first study. This paper aims to analyse the geographic and socio-demographic disparities in uptake in the second trial and compare the results with the first trial. METHODS: Inhabitants of the Stockholm region born in 1940 and 1941 were randomised 1:1 to be invited to screening or serve as controls. Medical history, blood samples and single-lead-ECG were collected. Invitee's residential parish was used for geo-mapping analysis of the geographical disparities in participation, using hierarchical Bayes methods. Individual data for participants and non-participants were obtained for the socioeconomic variables: educational level, disposable income, immigrant and marital status. RESULTS: Higher participation was observed in those with higher education, high income, among non-immigrants and married individuals. Participation between the first and second studies improved significantly, where additional screening sites were introduced. These improvements were generally significant, in each population group according to socio-demographic characteristics. CONCLUSION: Decentralisation of screening sites in an atrial fibrillation screening program yielded a significantly positive impact on screening uptake. Adding local screening sites in areas with low uptake had beneficial impact on participation across a wide spectrum of socio-demographic groups. Decentralised screening substantially increased the screening uptake in deprived areas.

Disease mapping of early- and late-stage cancer to monitor inequalities in early detection: a study of cutaneous malignant melanoma.

We consider disease mapping of early- and late-stage cancer, in order to identify and monitor inequalities in early detection. Our method is demonstrated by mapping cancer incidence at high geographical resolution using data on 10,302 cutaneous malignant melanoma (CMM) cases within the 3.7 million population of South-West Sweden. The cases were geocoded into small-areas, each with a population size between 600 and 2600 and accessible socio-demographic data. Using the disease mapping application Rapid Inquiry Facility (RIF) 4.0, we produced regional maps to visualise spatial variations in stage I, II and III-IV CMM incidences, complemented by local maps to explore the variations within two urban areas. Pronounced spatial disparities in stage I CMM incidence were revealed by the regional and local maps. Stage I CMM incidence was markedly higher in wealthier small-areas, in particular within each urban area. A twofold higher stage I incidence was observed, on average, in the wealthiest small-areas (upper quintile) than in the poorest small-areas (lower quintile). We identified in the regional map of stage III-IV CMM two clusters of higher or lower than expected late-stage incidences which were quite distinct from those identified for stage I. In conclusion, our analysis of CMM incidences supported the use of this method of cancer stage incidence mapping for revealing geographical and socio-demographic disparities in cancer detection.

Rational targeting of population groups and residential areas for colorectal cancer screening.

BACKGROUND: Sociodemographic and spatial disparities in incidence and mortality burden of colorectal cancer (CRC) are important to consider in the implementation of population screening, in order to achieve expected benefit and not increase health inequities. Analytic methods should be adapted to provide rational support for targeted interventions. METHODS: CRC incidence rates by tumor stage (I-IV) and location (colon vs. rectum) were analyzed for the time period 2008-2016 within a screening-relevant age interval of 55-74 years for the population of South and West Sweden, where screening is planned for. The study population was stratified by sex, country of birth, educational level (for Swedish-born citizens) and residential area. We also estimated disparities in excess mortality from CRC across groups of patients accordant to relevant population groups. RESULTS: The analyses were based on 8961 patients with a first CRC diagnosis. There were marked socioeconomic gradients in the stage II-IV CRC incidence rates among Swedish-born men and women. Compared to men with high educational level, the incidence rate ratios (IRRs) of stage II, III, and IV CRC in men with low educational level were 1.38 (95% confidence interval 1.18, 1.62), 1.09 (0.95, 1.26), and 1.18 (1.02, 1.37), respectively. In women, the corresponding figures were 1.26 (1.06, 1.51), 1.19 (1.01, 1.39), and 1.45 (1.20, 1.80). The groups of patients with low educational level showed relatively high excess mortality burdens from CRC. CONCLUSIONS: Our analytic approach provided rational support for targeted intervention when implementing CRC screening, aiming at optimizing participation in groups with low educational level.

A prospective 5-year follow-up after population-based systematic screening for atrial fibrillation.

Aims: Thrombo-embolic stroke risk in atrial fibrillation (AF) is significantly reduced with oral anticoagulant (OAC) treatment. Atrial fibrillation is often asymptomatic (silent) and therefore undiagnosed. The long-term course of silent AF as well as OAC treatment adherence after AF screening is not known. We aim at studying long-term adherence to OAC treatment, AF symptoms, and stroke incidence on population level after systematic AF screening. Methods and results: All inhabitants in a Swedish municipality who were born in 1934 and 1935 (n = 1335) were invited to participate in an AF screening trial between 2010 and 2012. Participants with a previously known or screening-detected AF were invited to a 5-year follow-up. Time trends of ischaemic stroke incidence were compared for population groups residing in the intervention municipality and in a surrounding control area where no AF screening trial was carried out. After the screening procedure, 103 of 121 participants (85%) with AF were treated with OAC. At the follow-up examination, 94 of 106 living patients (88%) were still on OAC treatment. Among the 23 long-term surviving patients who were diagnosed with paroxysmal AF during screening, 6 had developed permanent silent AF. The incidence of ischaemic stroke between ages 76-80 years declined significantly after the AF screening trial in the intervention area (P = 0.003) but not in the control area. Conclusion: Adherence to OAC treatment 5 years after AF screening was high. Silent AF has a natural course similar to symptomatic AF. The observed incidences of ischaemic stroke suggest a beneficial population-level effect of systematic AF screening.

Spatial disparities in melanoma incidence and prognosis with consideration to stage at diagnosis, gender and marital status.

Screening strategies need to consider differences in late-stage disease detection linked to socio-demographic and geographic factors. We specifically addressed disparity in melanoma stage at diagnosis linked to residential municipality, gender and marital status within the middle- and old-age population of southern and western Sweden. Population-based registers were used to identify the melanoma cases diagnosed in 2004-2013 (n=7,417). Disease mapping for each population group based on gender and marital status showed marked spatial disparities in melanoma incidences and the overall patterns differed by stage at diagnosis. The incidence of early-stage melanoma was markedly higher in the western region, whereas the incidence of late-stage melanoma was markedly higher in the southern region except for married women. Excess mortality among cases was observed to be higher in the southern than in the western region, with significant regional differences for the married male cases and the unmarried female cases.

Geographic and socio-demographic differences in uptake of population-based screening for atrial fibrillation: The STROKESTOP I study.

BACKGROUND: The rationale behind screening for atrial fibrillation (AF) is to prevent ischemic stroke. Socio-demographic differences are expected to affect screening uptake. Geographic differences may provide further insights leading to targeted interventions for improved uptake. The objective of this study was to evaluate geographic and socio-demographic differences in uptake of AF screening in the population-based study STROKESTOP I. METHODS: STROKESTOP was carried out in two Swedish counties with a total population of 2.3 million inhabitants. Half of the residents aged 75-76years were randomized to the screening arm: invitation to clinical examination followed by ambulant ECG recording. Information on each invited person's residential parish (n=157) was used. On parish-level, aggregated data for the participants and non-participants, respectively, were obtained with respect to socioeconomic variables: educational level, disposable income, immigrant and marital status. Geo-maps displaying participation ratios were estimated by hierarchical Bayes methods. RESULTS: The overall participation rate was similar in men and women but lower in Stockholm, 47.6% (5665/11,903) than in Halland, 61.2% (1495/2443). Participation was clearly associated with the socioeconomic variables. Participation not taking into account socioeconomy varied more markedly across the parishes in the Stockholm county (range: 0.65-1.26) than in the Halland county (0.94-1.27). After adjustment for socioeconomic variables, a geographic variation remained in Stockholm, but not in Halland. CONCLUSION: Participation in AF screening varied according to socioeconomic conditions. Geographic variation in participation was marked in the Stockholm county, with only one screening clinic. Geo-mapping of participation yielded useful information needed to intervene for improved screening uptake.

Overweight at four years of age in a Swedish birth cohort: influence of neighbourhood-level purchasing power.

BACKGROUND: A number of child/parental factors have been shown to be significant predictors of childhood overweight, although a better understanding of possible contextual influences of neighbourhood-level characteristics might provide new insights leading to tailored, targeted interventions. The aim of this study was to explore the impact of neighbourhood purchasing power and its relationship with other known risk factors related to childhood overweight in a prospective birth cohort. METHODS: A prospective, population-based, birth-cohort study was conducted in south-western Sweden, comprising 2,666 infants born in 2007-2008. Childhood overweight was assessed by body mass index (BMI) data from follow-up examinations at four years of age (n = 2,026) and overweight defined according to the International Obesity Task Force. Using logistic regression analysis, the influential child/parental predictors were identified from the candidate predictors, viz. child's gender, as well as birth weight adjusted for gestational age and parental factors at recruitment, including maternal smoking status, maternal BMI (before pregnancy), paternal BMI and parental educational level. The children's residential parishes at follow-up were stratified by parish-level household purchasing power (<10 %, 10-19.9 %, 20-29.9 % and ≥30 % of all resident families with low purchasing power) and the "contextual" influence was analysed. In each such neighbourhood stratum, the adjusted overweight ratio (AOR), i.e. the ratio between the observed number of overweight children and the expected number, taking account of the influential child/parental predictors, was estimated. RESULTS: The prevalence of overweight at four years of age was 11.9 %. In the economically strongest neighbourhoods (i.e. <10 % of resident families with low purchasing power), the AOR was 0.60 (95 % confidence interval (CI): 0.34-0.98). The corresponding empirically Bayes-adjusted AOR was 0.73 (95 % CI: 0.46-1.02; 97 % posterior probability of AOR <1). In the other neighbourhood strata, the statistical evidence of a deviant AOR was weaker. CONCLUSION: The economically strongest neighbourhoods had a lower prevalence than expected of overweight at four years of age. This finding should prompt studies to acquire more knowledge of potentially modifiable factors that differ between neighbourhoods and are related to childhood overweight, providing a basis for tailored, targeted interventions.

Cutaneous malignant melanoma show geographic and socioeconomic disparities in stage at diagnosis and excess mortality.

Background Preventive measures are needed to counteract the increasing burden of cutaneous malignant melanoma (CMM). As a basis for rational melanoma prevention, we investigated geographic differences and impact from socioeconomic factors related to incidence, clinical stage at diagnosis and outcome. Material and methods All patients with primary invasive CMM diagnosed in 2004-2013 in the southern and the western Swedish health care regions with a population of 2.9 million adults were eligible for the study. Population-based data were obtained from the national Cancer Register and the national Melanoma Quality Register. Geographic and socioeconomic differences in incidence per stage at diagnosis were mapped and correlated to excess mortality. Results Disease mapping based on 9743 cases in 99 municipalities and 20 metropolitan districts showed marked, regional disparities in stage-specific incidence of CMM. The incidence of stage I-II tumors was higher in the western health care region, whereas the incidence of stage III-IV CMMs was higher in the southern region. The divergent incidence patterns per stage at diagnosis were consistent across population strata based on educational level. The geographic disparities in CMM stage influenced relative survival with an excess five-year mortality ratio in the southern region versus the western region of 1.49 (95% confidence interval 1.22-1.82). The excess mortality ratio for patients with low versus high educational level was 1.81 (1.37-2.40). Conclusion Residential region and educational level influenced CMM stage and, thereby, excess mortality. These observations suggest that geographic as well as socioeconomic data should be considered in prevention of CMM.

Influence of neighbourhood purchasing power on breastfeeding at four months of age: a Swedish population-based cohort study.

BACKGROUND: Parental socioeconomic status (SES) is an important determinant in child health, influencing beneficial factors such as breastfeeding. A better understanding of the influence of neighbourhood-level SES measures, relating to spatial determinants, might lead to targeted actions to promote breastfeeding during infancy. METHODS: A cross-sectional study analysis the association between breastfeeding at four months of age and neighbourhood purchasing power, taking account of individual-level variables including maternal age, smoking and parental level of education. Data were obtained from a prospective population- based cohort study recruited from birth in 2007-2008 in the Halland region, southwestern Sweden. Questionnaire data on the individual-level variables and the outcome variable of breastfeeding at four months (yes/no) were used (n=2,407). Each mother was geo-coded with respect to her residential parish (there are 61 parishes in the region) and then stratified by parish-level household purchasing power. It emerged that four neighbourhood characteristics were reasonable to use, viz. <10%, 10-19%, 20-29% and ≥ 30% of the resident families with low purchasing power. RESULTS: The proportion of mothers not breastfeeding at four months of age showed a highly significant trend across the neighbourhood strata (p=0.00004): from 16.3% (< 10% with low purchasing power) to 29.4% (≥ 30% with low purchasing power), yielding an OR of 2.24 (95% confidence interval: 1.45-3.16). After adjusting for the individual-level variables, the corresponding OR=1.63 (1.07-2.56) was significant and the trend across the strata was still evident (p=0.05). A multi-level analysis estimated that, in the neighbourhoods with ≥ 30% of the families with low purchasing power, 20% more mothers than expected, taking account of the individual-level factors, reported no breastfeeding at four months of age (≥ 95% posterior probability of an elevated observed-to-expected ratio). CONCLUSION: The neighbourhood purchasing power provided a spatial determinant of low numbers of mothers breastfeeding at four months of age, which could be relevant to consider for targeted actions. The elevated observed-to-expected ratio in the neighbourhoods with the lowest purchasing power points toward a possible contextual influence.

Uptake of atrial fibrillation screening aiming at stroke prevention: geo-mapping of target population and non-participation.

BACKGROUND: In a screening study for silent atrial fibrillation (AF), which is a frequent source of cardiac emboli with ischemic stroke, the proportion of non-participants was considerable and their clinical profile differed from the participants' profile. We intended to geo-map the target population and non-participation in an attempt to understand factors related to screening uptake and, thereby, obtain useful information needed to intervene for improved uptake. METHOD: In the municipality of Halmstad, Sweden, all residents born in 1934-1935 were invited to the screening study during April 2010 to February 2012. The total study group included 848 participants and 367 non-participants from 12 parishes. Geo-maps displaying participation, along with target-population-based geo-maps displaying proportion of immigrants and ischemic stroke incidence, were used. RESULTS: Smoothed non-participation ratios (SmNPR) varied from 0.81 to 1.24 across different parishes (SmNRP=1 corresponds to the expected participation based on the total study group). Among high risk individuals, the geographical variation was more pronounced (SmNPR range 0.75-1.51). Two parishes with higher share of immigrants and elevated population-based ischemic stroke incidence showed markedly lower participation, particularly among high-risk individuals. CONCLUSION: AF screening uptake varied evidently between parishes, particularly among high-risk individuals. Geo-mapping of target population and non-participation yielded useful information needed to intervene for improved screening uptake.

Tobacco use and caries risk among adolescents--a longitudinal study in Sweden.

BACKGROUND: Smoking and the use of smokeless tobacco have a detrimental impact on general and oral health. The relationship to dental caries is however still unclear. As caries is a multi-factorial disease with clear life-style, socio-economic and socio-demographic gradients, the tobacco use may be a co-variable in this complex rather than a direct etiological factor. Our aim was to analyze the impact of tobacco use on caries incidence among adolescents, with consideration to socio-economic variables by residency, using epidemiological data from a longitudinal study in the region of Halland, Sweden. METHODS: The study population consisted of 10,068 adolescents between 16-19 years of age from whom yearly data on caries and tobacco use (cigarette smoking and use of smokeless tobacco) were obtained during the period 2006-2012. Reported DMFS increment between 16 and 19 years of age (∆DMFS) for an individual was considered as the primary caries outcome. The outcome data were compared for self-reported never vs. ever users of tobacco, with consideration to neighborhood-level socio-economy (4 strata), baseline (i.e., 16 years of age) DMFS and sex. The region consists of 65 parishes with various socio-economic conditions and each study individual was geo-coded with respect to his/her residence parish. Neighborhood (parish-level) socio-economy was assessed by proportion of residing families with low household purchasing power. RESULTS: ∆DMFS differed evidently between ever and never users of tobacco (mean values: 1.8 vs. 1.2; proportion with ∆DMFS > 0: 54.2% vs. 40.5%; p < 0.0001). Significant differences were observed in each neighborhood-level socio-economic stratum. Even after controlling for baseline DMFS and sex, ∆DMFS differed highly significantly between the ever and never users of tobacco (overall p < 0.0001). CONCLUSION: Tobacco use was clearly associated with increased caries increment during adolescence. Hence, this factor is relevant to consider in the clinical caries risk assessment of the individual patient as well as for community health plans dealing with oral health.

Electrochemical generation of electrophilic drug metabolites: characterization of amodiaquine quinoneimine and cysteinyl conjugates by MS, IR, and NMR.

The chemical reactivity of electrophilic metabolites usually prevents their detection in vivo since, by definition, they are relatively short-lived and are likely to undergo one or more structural modifications to form more stable final products. Electrochemical oxidation provides a means to generate reactive metabolites in an environment without the presence of such nucleophiles. This paper describes the results of our MS, MS/MS, NMR, IR, and computational studies on oxidation products (and conjugates) that have been generated electrochemically from the antimalarial agent amodiaquine. The electrophilic quinoneimine metabolite of amodiaquine was the major oxidation product following electrochemical oxidation at +600 mV. The absence of biological nucleophiles in the electrochemical experiment facilitated (i) the acquisition of a clean IR spectrum of the amodiaquine quinoneimine and (ii) the addition of biologically relevant nucleophiles under controlled conditions. The addition of cysteine gave four cysteinyl conjugates, while the addition of glutathione gave four glutathionyl conjugates. The product ion spectra of the conjugates formed in the electrochemical experiment were used to identify suitable fragments for selected reaction monitoring (SRM) to selectively search for these conjugates in human liver microsomal (HLM) incubations. The four cysteinyl conjugates, as well as the four glutathionyl conjugates, were also detected as metabolites in HLM. The experiment with cysteine was repeated on a preparative scale that allowed characterization of the major conjugates by (1)H NMR. Desethylamodiaquine, the major metabolite formed in human liver microsomes, was also generated electrochemically by oxidation of amodiaquine at +1200 mV followed by reduction at -800 mV. In conclusion, the EC-ESI/MS technique provides the unique opportunity to generate reactive metabolites in the absence of biological nucleophiles, which enables studies that can give insight into the nature of these reactive intermediates. Such knowledge is valuable for risk assessment of new compound classes and can be complementary to computer-based structure-activity relationships of carcinogenicity, mutagenicity, and teratogenicity.