Excess mortality for men and women above age 70 according to level of care during the first wave of COVID-19 pandemic in Sweden: A population-based study.

BACKGROUND: Both age and comorbidity are established risk factors for death among those infected with COVID-19. Because they often co-exist, it is difficult to assess if age is a risk factor on its own. METHODS: We used administrative register data of the total Swedish population from 01/2015 until 07/2020. We stratified the population aged 70+ into three groups according to level of care (in care homes, with home care, and in independent living). Within these groups, we explored the level of excess mortality in 2020 by estimating expected mortality with Poisson regression and compared it to observed levels. We investigated if excess mortality has been of the same magnitude in the three groups, and if age constitutes a risk factor for death during the pandemic regardless of level of care. FINDINGS: Individuals living in care homes experienced the highest excess mortality (75- >100% in April, 25-50% in May, 0-25% in June, depending on age). Individuals with home care showed the second highest magnitude (30-60% in April, 15-40% in May, 0-25% in June), while individuals in independent living experienced excess primarily at the highest ages (5-50% in April, 5-50% in May, 0-25% in June). Although mortality rates increased, the age-pattern of mortality during the pandemic resembled the age-pattern observed in previous years. INTERPRETATION: We found stepwise elevated excess mortality by level of care during the first wave of the COVID-19 pandemic in Sweden, suggesting that level of frailty or comorbidities plays a more important role than age for COVID-19 associated deaths. Part of our findings are likely attributable to differences in exposure to the virus between individuals receiving formal care and those living independently, and not only different case fatality between the groups. Although age is a strong predictor for mortality, the relative effect of age on mortality was no different during the pandemic than before. We believe this is an important contribution to the discussion of the pandemic, its consequences, and which groups need the most protection. FUNDING: This study was funded by the Swedish Research Council for Health, Working Life and Welfare (FORTE: grant 2016-07115).

Determinants of non-adherence to adjuvant endocrine treatment in women with breast cancer: the role of comorbidity.

PURPOSE: To examine factors associated with non-adherence during 5 years of endocrine treatment, including the possible influence of comorbidity burden and specific medical conditions. METHODS: From all women diagnosed with stage I-III, ER-positive breast cancer in Stockholm-Gotland, Uppsala-Örebro and Northern Sweden between 2006 and 2009, we included 4645 women who had at least one dispensation of tamoxifen or aromatase inhibitors (AIs) and 5 years of follow-up without distant recurrence. A medical possession ratio of < 80% was used to define non-adherence. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of non-adherence. RESULTS: During follow-up, 977 (21%) women became non-adherents. Non-adherence was associated with greater comorbidity burden assessed by Charlson comorbidity index (CCI) during follow-up (OR 1.43; 95% CI 1.08-1.88 for ≥ 2 additional scores compared to 0), pre-diagnostic HRT use (OR 1.99; 1.58-2.49), not married (OR 1.42; 1.23-1.64), high educational level (OR 1.25; 1.02-1.53 compared to lowest level), and use of symptom-relieving drugs. HER-2 positivity (OR 0.61; 0.45-0.81) and adjuvant chemotherapy (OR 0.42; 0.35-0.52) were associated with lower odds of non-adherence. Similar patterns were observed for the presence of lymph node metastasis, higher tumour grade, and use of AIs compared to tamoxifen. Myocardial infarction and chronic pulmonary disease was suggested as leading conditions associated with non-adherence in women with increasing CCI. CONCLUSION: We identified subgroups of women with breast cancer at increased risk of non-adherence. Our findings related to comorbidity suggest the importance of focusing on the presence of specific co-existing conditions when monitoring adherence.

Serum inflammatory markers in relation to prostate cancer severity and death in the Swedish AMORIS study.

Inflammation is a well-documented driver of cancer development and progression. However, little is known about its role in prostate carcinogenesis. Thus, we examined the association of C-reactive protein (CRP), haptoglobin, albumin and white blood cells (WBC) with prostate cancer (PCa) severity (defined by PCa risk category and clinicopathological characteristics) and progression (defined by PCa death). We selected 8,471 Swedish men with newly diagnosed PCa who had exposure measurements taken approximately 14 years prior to diagnosis. We calculated odds ratio (OR) and 95% confidence interval (CI) for the associations between the inflammatory markers and PCa severity using logistic regression, while Cox proportional hazard regression was used for the associations with overall and PCa death. Serum CRP levels were associated with increased odds of high risk and metastatic PCa, and high PSA levels (≥20 µg/L) (OR: 1.29; 95% CI: 1.06-1.56, 1.32; 1.05-1.65 and 1.51; 1.26-1.81, respectively). Similarly, higher haptoglobin levels were associated with increased odds of metastatic PCa, high PSA level and possibly high grade PCa (1.38; 1.10-1.74, 1.50; 1.17-1.93 and 1.25; 1.00-1.56, respectively). Albumin was positively associated with Gleason 4 + 3 tumour (1.38; 1.02-1.86) and overall death (HRunit increase in log : 1.60; 95% CI: 1.11-2.30), but inversely associated with high risk PCa and high PSA levels (≥20 µg/L) (0.71; 0.56-0.89 and 0.72; 0.5 9-0.90). WBC was associated with increased odds of T3-T4 PCa. Except for albumin, none of these markers were associated with PCa death or overall death. Systemic inflammation as early as 14 years prior to diagnosis may influence prostate cancer severity.

Increased prevalence of prior malignancies and autoimmune diseases in patients diagnosed with chronic myeloid leukemia.

We recently reported an increased incidence of second malignancies in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKI). To elucidate whether this increase may be linked, not to TKI but rather to a hereditary or acquired susceptibility to develop cancer, we estimated the prevalence of malignancies, autoimmune disease (AD) and chronic inflammatory disease (CID) in CML patients prior to their CML diagnosis. Nationwide population-based registers were used to identify patients diagnosed with CML in Sweden 2002-2012 and to estimate the prevalence of other malignancies, AD and CID prior to their CML diagnosis. For each patient with CML, five matched controls were selected from the general population. Conditional logistic regression was used to calculate odds ratios (OR). Nine hundred and eighty-four CML patients were assessed, representing more than 45 000 person-years of follow-up. Compared with matched controls, the prevalence of prior malignancies and AD was elevated in CML patients: OR 1.47 (95% confidence interval (CI) 1.20-1.82) and 1.55 (95% CI 1.21-1.98), respectively. No associations were detected between CML and previous CID. An increased prevalence of other malignancies and AD prior to the diagnosis of CML suggest that a hereditary or acquired predisposition to cancer and/or autoimmunity is involved in the pathogenesis of CML.

Review of 103 Swedish Healthcare Quality Registries.

BACKGROUND AND OBJECTIVES: In the past two decades, an increasing number of nationwide, Swedish Healthcare Quality Registries (QRs) focusing on specific disorders have been initiated, mostly by physicians. Here, we describe the purpose, organization, variables, coverage and completeness of 103 Swedish QRs. METHODS: From March to September 2013, we examined the 2012 applications of 103 QRs to the Swedish Association of Local Authorities and Regions (SALAR) and also studied the annual reports from the same QRs. After initial data abstraction, the coordinator of each QR was contacted at least twice between June and October 2013 and asked to confirm the accuracy of the data retrieved from the applications and reports. RESULTS: About 60% of the QRs covered ≥80% of their target population (completeness). Data recorded in Swedish QRs include aspects of disease management (diagnosis, clinical characteristics, treatment and lead times). In addition, some QRs retrieve data on self-reported quality of life (EQ5D, SF-36 and disease-specific measures), lifestyle (smoking) and general health status (World Health Organization performance status, body mass index and blood pressure). CONCLUSION: Detailed clinical data available in Swedish QRs complement information from government-administered registries and provide an important source not only for assessment and development of quality of care but also for research.

Anti-androgen prescribing patterns, patient treatment adherence and influencing factors; results from the nationwide PCBaSe Sweden.

PURPOSE: Adherence has not been studied in male oncology populations. The aim of this study on both the prescriber and user perspectives in prostate cancer treatment was to analyse real-life prescribing patterns of anti-androgens (AA), primarily bicalutamide, and factors influencing the patients' adherence to treatment. METHODS: A nationwide clinical cohort of incident prostate cancer, PCBaSe, was linked to the Swedish Prescribed Drug Register. Men with a planned first line monotherapy AA treatment were identified; dosages and extent of off-label treatment were investigated. Cumulative incidence proportions for reasons for drug discontinuation were calculated. Factors potentially influencing adherence were explored using the medical possession ratio based on the individual prescribed daily dose. RESULTS: First line monotherapy AA was planned in 4.4 % of all incident cases and in 2.1 % of low risk disease cases. Among 1,406 men prescribed bicalutamide, 1,109 (79 %) received the approved daily dose of 150 mg. Discontinuation reasons differed with disease severity. Off-label, low-dose prescription associated with age above 75 years and disease categorised as low risk was noted in 297 men (21 %). Sixty percent of the men adhered well, i.e. to ≥80 %. Age above 75 years and less severe disease were both negatively associated with adherence. CONCLUSIONS: Patient age and tumour risk group influenced the prescriber's choice of dose, pointing to important issues for critical reflection. Possible over-treatment was noted in low risk disease. Interventions to increase adherence in older men and in men with less severe disease are worth considering after critically reviewing the appropriateness of the treatment indication, especially in the latter case.

Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995-2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry data.

BACKGROUND: Cancer survival is a key measure of the effectiveness of health-care systems. Persistent regional and international differences in survival represent many avoidable deaths. Differences in survival have prompted or guided cancer control strategies. This is the first study in a programme to investigate international survival disparities, with the aim of informing health policy to raise standards and reduce inequalities in survival. METHODS: Data from population-based cancer registries in 12 jurisdictions in six countries were provided for 2·4 million adults diagnosed with primary colorectal, lung, breast (women), or ovarian cancer during 1995-2007, with follow-up to Dec 31, 2007. Data quality control and analyses were done centrally with a common protocol, overseen by external experts. We estimated 1-year and 5-year relative survival, constructing 252 complete life tables to control for background mortality by age, sex, and calendar year. We report age-specific and age-standardised relative survival at 1 and 5 years, and 5-year survival conditional on survival to the first anniversary of diagnosis. We also examined incidence and mortality trends during 1985-2005. FINDINGS: Relative survival improved during 1995-2007 for all four cancers in all jurisdictions. Survival was persistently higher in Australia, Canada, and Sweden, intermediate in Norway, and lower in Denmark, England, Northern Ireland, and Wales, particularly in the first year after diagnosis and for patients aged 65 years and older. International differences narrowed at all ages for breast cancer, from about 9% to 5% at 1 year and from about 14% to 8% at 5 years, but less or not at all for the other cancers. For colorectal cancer, the international range narrowed only for patients aged 65 years and older, by 2-6% at 1 year and by 2-3% at 5 years. INTERPRETATION: Up-to-date survival trends show increases but persistent differences between countries. Trends in cancer incidence and mortality are broadly consistent with these trends in survival. Data quality and changes in classification are not likely explanations. The patterns are consistent with later diagnosis or differences in treatment, particularly in Denmark and the UK, and in patients aged 65 years and older. FUNDING: Department of Health, England; and Cancer Research UK.

Prenatal ultrasound exposure and children's school performance at age 15-16: follow-up of a randomized controlled trial.

OBJECTIVE: To evaluate the association between prenatal ultrasound exposure and school performance at 15-16 years of age. METHODS: The study population consisted of children born to women who participated in a randomized controlled trial on the second-trimester ultrasound examination in Sweden from 1985 to 1987. Information about the children's grades when graduating from primary school and information on socioeconomic factors was obtained from Swedish nationwide registers. Comparisons were made using linear and logistic regression analyses according to randomization to ultrasound, ultrasound exposure in the second trimester and ultrasound exposure at any time during pregnancy. Boys and girls were analyzed separately. RESULTS: Of the 4756 singleton children from the randomized trial, we identified 4458 (94%) in the National School Register. There were no statistically significant differences in school performance for boys or girls according to randomization or exposure to ultrasound in the second trimester. Compared to those who were unexposed, boys exposed to ultrasound at least once at any time during fetal life had a tendency towards lower mean school grades in general (-4.39 points; 95% CI, -9.59 to 0.81 (max possible, 320) points) and in physical education (-0.45 points; 95% CI, -0.91 to 0.01 (max possible, 20) points), but the differences did not reach significance. CONCLUSION: In general, routine ultrasound examination in the second trimester had no effect on overall school performance in teenagers.

Parity and risk of stomach cancer by sub-site: a national Swedish study.

We investigated stomach cancer risk by anatomic sub-site in relation to parity, as a marker for higher exposure to sex hormones, in a case-control study, nested within a cohort of 2,406,439 Swedish women born in 1925 or later and followed from 1970 or age 30 until emigration, death, any cancer diagnosis, or through 2004, whichever occurred first. We identified 286 cardia and 2498 non-cardia stomach cancer cases with five matched controls for each case. Cross-linkage with the Multi-Generation Register provided information about reproductive history. Using conditional logistic regression models for estimating odds ratios (ORs) and corresponding 95% confidence intervals (CIs), adjusted for education level and occupation, we found no association between any aspect of parity and non-cardia stomach cancer (OR=1.01, 95% CI 0.89-1.15, comparing parous with nulliparous women). However, a 30% risk reduction for postmenopausal cardia cancer (OR=0.7, 95% CI 0.4-1.0) was noted among parous relative to nulliparous women and the risk for premenopausal cardia cancer fell with increasing number of children (P for trend=0.04). Our results indicate that exposure to female sex hormones does not protect against non-cardia stomach cancer and does not explain male predominance. The observed moderate inverse relationship between parity and cardia cancer may be mediated by non-hormonal factors and warrants further study.

Risk of hypertension amongst Swedish male snuff users: a prospective study.

BACKGROUND: The scientific evidence on whether long-term use of snuff is associated with high blood pressure is limited, inconsistent and based only on cross-sectional data. OBJECTIVE: We aimed at studying the risk of hypertension in relation to long-term use of snuff based on longitudinal data. DESIGN: Repeated health check-ups were offered to all employees in the Swedish construction industry between 1978 and 1993. Blood pressure was measured at the health check-up and information on tobacco use and other risk factors was collected through questionnaires. SETTING: In total, 120 930 never smoking men with information on blood pressure and snuff use at baseline were included. The association of high blood pressure and snuff use at baseline was estimated by logistic regression. Further, 42 055 men were identified as normotensive at baseline and had at least one subsequent health check-up. Through repeated blood pressure measurements and linkage to the Swedish National Inpatient Register, information on hypertension was obtained. Relative risk estimates were derived from Cox proportional hazards regression model. RESULTS: Almost 30% of all men had used snuff. The adjusted odds ratio of high blood pressure amongst snuff users at baseline was 1.23 (95% CI 1.15-1.33) compared to never snuff users. The relative risk of high blood pressure during follow-up was 1.39 (95% CI 1.08-1.79) amongst snuff users and 1.36 (95% CI 1.07-1.72) for hypertension as recorded in the Inpatient Register. CONCLUSION: Use of Swedish moist snuff appears to be associated with a moderately increased risk of hypertension.

Correlation of umbilical cord blood haematopoietic stem and progenitor cell levels with birth weight: implications for a prenatal influence on cancer risk.

We examined the relation with birth weight and umbilical cord blood concentrations of haematopoietic stem and progenitor populations in 288 singleton infants. Across the whole range of birth weight, there was a positive relation between birth weight and CD34+CD38(-) cells, with each 500 g increase in birth weight being associated with a 15.5% higher (95% confidence interval: 1.6-31.3%) cell concentration. CD34+ and CD34+c-kit+ cells had J-shaped relations and CFU-GM cells had a U-shaped relation with birth weight. Among newborns with >or=3000 g birth weights, concentrations of these cells increased with birth weight, while those below 3000 g had higher stem cell concentrations than the reference category of 3000-3499 g. Adjustment for cord blood plasma insulin-like growth factor-1 levels weakened the stem and progenitor cell-birth weight associations. The positive associations between birth weight and stem cell measurements for term newborns with a normal-to-high birth weight support the stem cell burden hypothesis of cancer risk.

Scholastic achievement at age 16 and risk of schizophrenia and other psychoses: a national cohort study.

BACKGROUND: There is abundant evidence that schizophrenia is associated with cognitive deficits in childhood. However, previous studies investigating school performance have been inconclusive. Furthermore, there are several biological and social factors that could confound the association. We investigated whether school performance at age 16 is associated with risk of adult schizophrenia and other psychoses in a large national cohort, while controlling for multiple confounders. METHOD: Using a national sample of 907 011 individuals born in Sweden between 1973 and 1983, we used Cox regression to assess whether scholastic achievement at age 15-16 predicted hospital admission for psychosis between ages 17 and 31, adjusting for potential confounders. RESULTS: Poor school performance was associated with increased rates of schizophrenia [hazard ratio (HR) 3.9, 95% confidence interval (CI) 2.8-5.3], schizo-affective disorder (HR 4.2, 95% CI 1.9-9.1) and other psychoses (HR 3.0, 95% CI 2.3-4.0). Receiving the lowest (E) grade was significantly associated with risk for schizophrenia and other psychoses in every school subject. There was no evidence of confounding by migrant status, low birthweight, hypoxia, parental education level or socio-economic group. CONCLUSIONS: Poor school performance across all domains is strongly associated with risk for schizophrenia and other psychoses.

Long-term use of Swedish moist snuff and the risk of myocardial infarction amongst men.

BACKGROUND: The scientific evidence on cardiovascular risks associated with long-term use of snuff is limited and inconclusive. The use of this smokeless tobacco has increased in recent decades, and adverse health effects associated with snuff use could be of great public health concern. OBJECTIVE: We aimed to study whether long-term use of snuff affects the risk of myocardial infarction. DESIGN: Between 1978 and 1993 all construction workers in Sweden were offered repeated health check-ups by the Swedish Construction Industry's Organization for Working Environment Safety and Health. A cohort was created with information on tobacco use and other risk factors, collected through questionnaires. SETTING: In total, 118,395 nonsmoking men without a history of myocardial infarction were followed through 2004. Information on myocardial infarction morbidity and mortality was obtained from national registers. Relative risk estimates were derived from Cox proportional hazards regression model, with adjustment for age, body mass index and region of residence. RESULTS: Almost 30% of the men had used snuff. In total, 118 395 nonsmoking men without a history of myocardial infarction were followed through 2004. The multivariable-adjusted relative risks for ever snuff users were 0.91 (95% confidence interval, 0.81-1.02) for nonfatal cases and 1.28 (95% confidence interval, 1.06-1.55) for fatal cases. Heavy users (>or=50 g day(-1)) had a relative risk of fatal myocardial infarction of 1.96 (95% confidence interval, 1.08-3.58). Snuff use increased the probability of mortality from cardiovascular disease amongst nonfatal myocardial infarction patients. CONCLUSION: Our results indicate that snuff use is associated with an increased risk of fatal myocardial infarction.

Temporal trends in non-small cell lung cancer survival in Sweden.

We modeled temporal trends in the 1- and 5-year survival of 32 499 patients with adenocarcinoma and squamous cell carcinoma of the lung in the Swedish Cancer Register between 1961 and 2000. The 1-year relative survival for adenocarcinoma improved from 37% for patients diagnosed 1961-1965 to 45% for those diagnosed 1996-2000 and from 39 to 45% for squamous cell carcinoma. The adjusted excess mortality ratios for the period 1996-2000 compared with 1961-1965 were 0.80 for adenocarcinoma and 0.81 for squamous cell carcinoma. Thus, a previous report in a Dutch study of a relatively worsening prognosis for adenocarcinoma over time could not be confirmed.

Coronary angioplasty and cancer risk: a population-based cohort study in Sweden.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) has become the reperfusion method of choice in patients with coronary artery disease. This sometimes complicated and lengthy procedure is performed using fluoroscopy and cineradiography or digital imaging, which may result in considerable exposure to ionizing radiation. Possible cancer risks in PTCA patients have been discussed, but never before examined in a population-based setting. OBJECTIVE: To assess the cancer risks following PTCA. METHODS: A cohort study was carried out based on nationwide registration of all coronary angioplasty procedures in Sweden between 1989 and 1998. The study encompassed a total of 23,097 PTCA patients followed up for cancer outcomes in the Swedish Cancer Register until December 31, 2000. The mean and median follow-up times were 4.8 and 4.5 years, respectively. The main outcome measures were standardized incidence ratios of cancer. RESULTS: Except for a transient excess of lung cancers, observed number of cancers in patients who had undergone coronary angioplasty did not differ from those expected in the general population. If anything, the overall cancer risk was lower in the PTCA group (SIR 0.94; 95% CI 0.88-0.99). In particular, no increased risks were detected for leukemias or thyroid cancer. CONCLUSION: There was no indication of increased risks of leukemia or cancers overall in PTCA patients.

Effect of delays on prognosis in patients with non-small cell lung cancer.

BACKGROUND: The effect of delay on survival in lung cancer remains uncertain. It is suggested that prompt management of non-small cell lung cancer (NSCLC) can influence prognosis. This study was undertaken to examine the relation between delay and prognosis in patients with NSCLC and to investigate the delay time from first symptom and from first hospital visit to start of treatment. METHODS: Two types of delay (symptom to treatment delay and hospital delay) were investigated in 466 patients treated for NSCLC at two institutions in central Sweden. Delays in relation to clinical characteristics were compared and the effects of delay times and other relevant factors on survival were assessed in multivariate analyses. RESULTS: Thirty five per cent of patients received treatment within 4 weeks of the first hospital visit and 52% within 6 weeks. Median symptom to treatment delay was 4.6 months and median hospital delay 1.6 months. Older age, advanced tumour stage, and non-surgical treatment were independently related to poor survival. Both prolonged hospital delay and symptom to treatment delay provided additional information when considered separately. In a final multivariate model only increased symptom to treatment delay gave significant information of a better prognosis. There was an association between a short delay and a poor prognosis which was most pronounced in patients with advanced disease. CONCLUSION: When considering the whole study population and all stages of tumour together, shorter delay was associated with a poorer prognosis. This is likely to reflect the fact that patients with severe signs and symptoms receive prompt treatment. These findings indicate that the waiting time for treatment in patients with NSCLC is longer than recommended.

Seasonal variation in the diagnosis of cancer: a study based on national cancer registration in Sweden.

Data from the Swedish Cancer Register 1987-1996 were used to examine seasonal trends in the diagnosis of cancer. For melanomas, prostate, breast and thyroid cancer there were clear seasonal variations with reductions in the number of cases reported during the summer and December that are likely to reflect mainly hospital delays.

Quality of life following lung cancer surgery.

BACKGROUND: Patients with non-small cell bronchogenic carcinoma have a limited survival. Quality of life (QoL) is therefore an issue of importance in this group of patients. The aim of the present study was to evaluate QoL in lung cancer patients after open surgery. METHODS: During a 4 year period (1997-2000) 194 patients with primary bronchogenic carcinoma of the lung underwent surgery at the Department of Thoracic and Cardiovascular Surgery in Uppsala, Sweden; 132 patients were alive on 1 April 2001. These patients received the Short Form-36 (SF-36) health questionnaire, Hospital Anxiety and Depression (HAD) scale, and special questions related to pulmonary symptoms (response rate 85%). Patients who underwent coronary bypass surgery (CABG) served as a comparison group (response rate 91%). Corresponding estimates of QoL in healthy controls were obtained from the SF-36 manual for the Swedish population. RESULTS: Lung cancer patients differed from CABG patients in only one subgroup of the SF-36 (role physical), but had poorer QoL than healthy controls. No difference in anxiety was found between the lung cancer patients and the CABG patients, but the latter were more likely to suffer from depression (5.0% v 3.0%). Current smokers scored lower in the mental health dimension assessment. CONCLUSION: Lung cancer patients who undergo open traditional surgical resection have a QoL comparable to that of CABG patients. Lung cancer patients have poorer physical function because of reduced pulmonary function, but show no sign of increased anxiety or depression. Those who continued to smoke after surgery had impaired mental health.