Cancer diagnostic delays and travel distance to health services: A nationwide cohort study in Denmark

BackgroundThis study aims to investigate the association between distance to health services and intervals in the cancer diagnostic pathway, and explore whether the diagnostic difficulty of the cancer influences this association.MethodA nationwide cohort study was conducted based on data from both questionnaires and registries. Danish cancer patients diagnosed in 2005–2016 and their general practitioner (GP) were included if enrolled in the Danish Cancer in Primary Care (CaP) cohort (n = 37,872). The CaP cohorts provided data on intervals assessed by patients and GPs. The Geographical Information System (GIS) was used to calculate travel distances from the residence of the patient to their GP surgery and to the hospital of diagnosis.ResultsLonger travel distance to the hospital of diagnosis was associated with longer diagnostic interval. This association was strongest in the period before the implementation of Cancer Patient Pathways (CPP) in 2010. Patients with a cancer categorised as ´hard to diagnose´ contributed mostly to the association. Longer travel distance to the GP was associated with shorter patient interval and primary care interval for patients diagnosed with cancer types ´intermediate to diagnose´.ConclusionTravel distance to cancer diagnostic health care services was associated with interval length in the diagnostic pathway. This association was less pronounced in the period after introducing CPPs and also strongly depending of the underlying cancer type and symptomatology.     

Socioeconomic status and non-melanoma skin cancer: A nationwide cohort study of incidence and survival in Denmark

Background: The two main types of non-melanoma skin cancer differ with the pattern of exposure to ultraviolet radiation (UVR): basal cell carcinoma (BCC) appears to be more closely related to intermittent solar exposure and sunburn, while the risk for squamous cell carcinoma (SCC) is a result of lifetime cumulated exposure to UVR. As these exposures may differ by social position, we investigated its role in the risk for and survival after BCC and SCC diagnosed in Denmark in 1994–2006 with follow-up through 2006. Methods: The analyses were based on 52,166 cases of BCC and 5033 cases of SCC in a cohort of 3.7 million people born between 1925 and 1976 and residing in Denmark in 1992–2006. Information on cancer cases and socioeconomic indicators were obtained from population-based registries. We used log-linear Poisson regression models to estimate incidence rate ratios and cumulative relative survival to estimate survival up to 10 years after the first incident cases of BCC and SCC. Results: High socioeconomic status, measured by both education and disposable income, was strongly associated with a higher risk for BCC, whereas there was no association between SCC and educational level and only a weak association with income. In general, relative survival after BCC was better than after SCC; the pattern of survival was not affected by socioeconomic indicators. Conclusions: The observed pattern of social status and risk for non-melanoma skin cancer differed substantially for the two cancer types, supporting the hypothesis that they may have different aetiologies.     

Unplanned cancer presentation in patients with psychiatric disorders: A nationwide register-based cohort study in Denmark

Unplanned presentation in the cancer pathway is more common in patients with psychiatric disorders than in patients without. More knowledge about the risk factors for unplanned presentation could help target interventions to ensure earlier diagnosis of cancer in patients with psychiatric disorders. This study aims to estimate the association between patient characteristics (social characteristics and coexisting physical morbidity) and cancer diagnosis following unplanned presentation among cancer patients with psychiatric disorders. We conducted a population-based register study including patients diagnosed with cancer in 2014–2018 and also registered with at least one psychiatric disorder in the included Danish registers (n = 26,005). We used logistic regression to assess patient characteristics associated with an unplanned presentation. Almost one in four symptomatic patients (23.6 %) with pre-existing psychiatric disorders presented unplanned in the cancer trajectory. Unplanned presentation was most common for severe psychiatric disorders, e.g. organic disorders and schizophrenia. Old age, male sex, living alone, low education, physical comorbidity, and non-attendance in primary care were associated with increased odds of unplanned presentation. In conclusion, several characteristics of patients with pre-existing psychiatric disorders were associated with unplanned presentation in the cancer trajectory; for some groups more than 40 % had an unplanned presentation. This information could be used to design targeted interventions for patients with pre-existing psychiatric disorders to ensure earlier diagnosis of cancer in this population.     

Infections in temporal proximity to HPV vaccination and adverse effects following vaccination in Denmark: A nationwide register-based cohort study and case-crossover analysis

BackgroundPublic trust in the human papilloma virus (HPV) vaccination programme has been challenged by reports of potential severe adverse effects. The reported adverse symptoms were heterogeneous and overlapping with those characterised as chronic fatigue syndrome (CFS) and have been described as CFS-like symptoms. Evidence suggests that CFS is often precipitated by an infection. The aim of the study was to examine if an infection in temporal proximity to HPV vaccination is a risk factor for suspected adverse effects following HPV vaccination.Methods and findingsThe study was a nationwide register-based cohort study and case-crossover analysis. The study population consisted of all HPV vaccinated females living in Denmark, born between 1974 and 2006, and vaccinated between January 1, 2006 and December 31, 2017. The exposure was any infection in the period ± 1 month around time of first HPV vaccination and was defined as (1) hospital-treated infection; (2) redemption of anti-infective medication; or (3) having a rapid streptococcal test done at the general practitioner. The outcome was referral to a specialised hospital setting (5 national HPV centres opened June 1, 2015) due to suspected adverse effects following HPV vaccination. Multivariable logistic regression was used to estimate the association between infection and later HPV centre referral. The participants were 600,400 HPV-vaccinated females aged 11 to 44 years. Of these, 48,361 (9.7%) females had a hospital-treated infection, redeemed anti-infective medication, or had a rapid streptococcal test ± 1 month around time of first HPV vaccination. A total of 1,755 (0.3%) females were referred to an HPV centre. Having a hospital-treated infection in temporal proximity to vaccination was associated with significantly elevated risk of later referral to an HPV centre (odds ratio (OR) 2.75, 95% confidence interval (CI) 1.72 to 4.40; P < 0.001). Increased risk was also observed among females who redeemed anti-infective medication (OR 1.56, 95% CI 1.33 to 1.83; P < 0.001) or had a rapid streptococcal test (OR 1.45, 95% CI 1.10 to 1.93; P = 0.010). Results from a case-crossover analysis, which was performed to adjust for potential unmeasured confounding, supported the findings. A key limitation of the study is that the HPV centres did not open until June 1, 2015, which may have led to an underestimation of the risk of suspected adverse effects, but stratified analyses by year of vaccination yielded similar results.ConclusionsTreated infection in temporal proximity to HPV vaccination is associated with increased risk for later referral with suspected adverse vaccine effects. Thus, the infection could potentially be a trigger of the CFS-like symptoms in a subset of the referred females. To our knowledge, the study is the first to investigate the role of infection in the development of suspected adverse effects after HPV vaccination and replication of these findings are needed in other studies.

Lene Wulff Krogsgaard and co-workers study temporal associations between infections and HPV vaccination.     

Risk of neurological diseases among survivors of electric shocks: a nationwide cohort study, Denmark, 1968-2008

Several studies suggest a link between electric injuries and neurological diseases, where electric shocks may explain elevated risks for neuronal degeneration and, subsequently, neurological diseases. We conducted a retrospective cohort study on the risk of neurological diseases among people in Denmark who had survived an electric accident in 1968-2008. The cohort included 3,133 people and occurrences of neurological diseases were determined by linkage to the nationwide population-based Danish National Register of Patients. The numbers of cases observed at first hospital contact in the cohort were compared with the respective rates of first hospital contacts for neurological diseases in the general population. We observed significantly increased risks for peripheral nerve diseases (standardized hospitalization ratio (SHR), 1.66; 95% confidence interval (CI), 1.22-2.22), for migraine (SHR, 1.80; 95% CI, 1.23-2.54), for vertigo (SHR, 1.60; 95% CI, 1.22-2.05), and for epilepsy (SHR, 1.45; 95% CI, 1.11-1.85). Only small numbers of cases of other neurological diseases were found, making the risk estimates unstable. These findings suggest an association between a single electric shock and increased risks for peripheral nerve diseases, migraines, vertigo, and epilepsy, but confirmation of these observations is needed.     

Risk of tuberculosis in dialysis patients: a nationwide cohort study

Background

The ability to identify individuals at increased risk of developing tuberculosis (TB) has important implications for public health policy and patient care. We conducted a general population historical cohort study in all Australian States and Territories to establish the risk of TB arising in people on chronic hemo- or peritoneal dialysis.

Methodology/Principal Findings

Cases of TB disease in patients receiving chronic dialysis were identified by record linkage using the Australia & New Zealand Dialysis and Transplant Registry (ANZDATA) and State and Territory TB notification databases 2001 to 2006. Main outcome measure was the relative risk of TB in people on dialysis, adjusted for TB incidence in country of birth, sex, age and indigenous status. A total of 6,276 cases of active TB were reported among 19,855,283 people living in Australia between 2001 and 2006. Among 14,506 patients on dialysis, 37 had a notification for TB disease after commencing dialysis, of whom 28 were culture positive. The incidence of TB was 66.8/100,000/year (95% CI 47.7 to 93.2) among people on dialysis and 5.7/100,000/year (95% CI 5.5 to 5.8) in the general population. The adjusted relative risk (aRR) of TB in people on dialysis was 7.8 (95% CI 3.3 to 18.7), and the aRR of culture positive TB was 8.6 (95% CI 3.9 to 19.3).

Conclusions/Significance

Patients on dialysis are at increased risk of TB. The final decision to screen for, and to treat, LTBI in individual dialysis patients will be influenced by a cumulative assessment of the risk of reactivation of TB and by assessment of risk factors for adverse effects of treatment.     

Mobile phones, heat shock proteins and cancer

There are several reports which indicate that electromagnetic radiation (such as from mobile phones) at non-thermal levels may elicit a biological effect in target cells or tissues. Whether or not these biological effects lead to adverse health effects, including cancer, is unclear. To date there is limited scientific evidence of health issues, and no mechanism by which mobile phone radiation could influence cancer development. In this paper, we develop a theoretical mechanism by which radiofrequency radiation from mobile phones could induce cancer, via the chronic activation of the heat shock response. Upregulation of heat shock proteins (Hsps) is a normal defence response to a cellular stress. However, chronic expression of Hsps is known to induce or promote oncogenesis, metastasis and/or resistance to anticancer drugs. We propose that repeated exposure to mobile phone radiation acts as a repetitive stress leading to continuous expression of Hsps in exposed cells and tissues, which in turn affects their normal regulation, and cancer results. This hypothesis provides the possibility of a direct association between mobile phone use and cancer, and thus provides an important focus for future experimentation.     

Cancer risks of dermatomyositis and polymyositis: a nationwide cohort study in Taiwan

Introduction  

The association of idiopathic inflammatory myositis (IIM) and malignancies has been reported, but rarely in Asian countries. Our aim was to investigate the risk of cancer among IIM patients without a prior history of malignancies, in Taiwan.     

Gout and the risk of dementia: a nationwide population-based cohort study

IntroductionUric acid was proposed to have anti-oxidant property and possible neuroprotective effects. We examined the association between gout and dementia with population database.MethodsThe study utilized the claims data from the nationwide representative sample of Taiwan National Health Insurance Research Database (NHIRD). We ascertained patients with gout and dementia covering vascular and non-vascular (including Alzheimer’s) subtypes using International Classification of Diseases Ninth Revision, Clinical Modification (ICD9-CM) codes. A control group matched on sex, age, and index date of gout patients was randomly sampled with a ratio of 1:4 from the same database for comparison.ResultsFrom 2002 to 2008, 28,769 gout patients who were older than 50 years old were identified, and 114,742 control patients was matched into the study. During follow-up, 7,119 patients developed dementia (1,214 with gout, and 5,905 without gout). After adjusting for age, sex, and relevant comorbidities, a Cox regression analysis showed that gout patients had a lower risk of developing non-vascular dementia (hazard ratio (HR): 0.77; 95% confidence interval (CI): 0.72 - 0.83; p < 0.001) and vascular dementia (HR: 0.76; 95% CI: 0.65 - 0.88; p < 0.001).ConclusionsPatients with gout have a lower risk of developing dementia. This phenomenon exists for both non-vascular and vascular types of dementia.     

Low-dose aspirin use and survival in breast cancer patients: A nationwide cohort study

BackgroundPreclinical evidence from breast cancer cell lines and animal models suggest that aspirin could have anti-cancer properties. In a large breast cancer patient cohort, we investigated whether post-diagnostic low-dose aspirin use was associated with a reduction in the risk of breast cancer-specific mortality.MethodsWe identified 15,140 newly diagnosed breast cancer patients within the Scottish Cancer Registry. Linkages to the Scottish Prescribing Information System provided data on dispensed medications and breast cancer-specific deaths were identified from National Records of Scotland Death Records. Time-dependent Cox regression models were used to calculate hazard ratios (HR) and 95% CIs for breast cancer-specific and all-cause mortality by post-diagnostic low-dose aspirin use. HRs were adjusted for a range of potential confounders including age at diagnosis, year of diagnosis, cancer stage, grade, cancer treatments received, comorbidities, socioeconomic status and use of statins. Secondary analysis investigated the association between pre-diagnostic low-dose aspirin use and breast cancer-specific and all-cause mortality.ResultsPost-diagnostic users of low-dose aspirin appeared to have increased breast cancer-specific mortality compared with non-users (HR 1.44, 95% CI 1.26, 1.65) but this association was entirely attenuated after adjustment for potential confounders (adjusted HR 0.92, 95% CI 0.75, 1.14). Findings were similar in analysis by increasing duration of use and in analysis of pre-diagnostic low-dose aspirin use.ConclusionIn this large nationwide study of breast cancer patients, we found little evidence of an association between post-diagnostic low-dose aspirin use and cancer-specific mortality.     

Hospital surgical volume and colorectal cancer survival in Norway: A nationwide cohort study

BackgroundStudies of hospital surgical volume and colorectal cancer survival are inconclusive. We investigated whether surgical volume was associated with survival of patients operated for colorectal cancer in Norway.MethodsUsing Cancer Registry of Norway data, we compared excess mortality from colorectal cancer by hospital surgical volume among 26,989 colon and 9779 rectal cancer patients diagnosed 2009–2020 and followed-up to 31.12.2021. Hospitals were divided into terciles according to their three-year average annual surgical volume; colon: low (< 22), middle (22–73), high (> 73); rectal: low (< 17), middle (17–38), high (> 38). We estimated excess hazard ratios (EHR) with flexible parametric models adjusted for age, year, stage, surgical urgency and surgery location (within/outside patient’s residential health trust).ResultsLow-volume hospitals had the highest proportion of late-stage or acutely operated colon cancer patients. Colon cancer patients operated at low- versus high-volume hospitals had significantly increased crude excess mortality (EHR = 1.30; 95 % CI = 1.14–1.48) but no difference after adjustment for age, year, and stage (EHR = 0.97; 0.85–1.11). High-volume hospitals had the highest proportion of late-stage rectal cancer patients and patients operated outside their residential area. Rectal cancer patients operated at low- versus high-volume hospitals did not have significantly different excess mortality before (EHR = 0.84; 0.64–1.10) or after (EHR = 1.03; 0.79–1.35) adjustment for age, year, stage, surgical urgency and surgery location. After accounting for case-mix, hospital surgical volume was not associated with excess mortality from colon (P = 0.40) or rectal cancer (P = 0.22).ConclusionLow hospital surgical volume was not associated with poorer colorectal cancer survival.     

Long-term mortality in patients with tuberculous meningitis: a Danish nationwide cohort study

Background

With high short-term mortality and substantial excess morbidity among survivors, tuberculous meningitis (TBM) is the most severe manifestation of extra-pulmonary tuberculosis (TB). The objective of this study was to assess the long-term mortality and causes of death in a TBM patient population compared to the background population.

Methods

A nationwide cohort study was conducted enrolling patients notified with TBM in Denmark from 1972–2008 and alive one year after TBM diagnosis. Data was extracted from national registries. From the background population we identified a control cohort of individuals matched on gender and date of birth. Kaplan-Meier survival curves and Cox regression analysis were used to estimate mortality rate ratios (MRR) and analyse causes of death.

Findings

A total of 55 TBM patients and 550 individuals from the background population were included in the study. Eighteen patients (32.7%) and 107 population controls (19.5%) died during the observation period. The overall MRR was 1.79 (95%CI: 1.09–2.95) for TBM patients compared to the population control cohort. TBM patients in the age group 31–60 years at time of diagnosis had the highest relative risk of death (MRR 2.68; 95%CI 1.34–5.34). The TBM patients had a higher risk of death due to infectious disease, but not from other causes of death.

Conclusion

Adult TBM patients have an almost two-fold increased long-term mortality and the excess mortality stems from infectious disease related causes of death.     

Mobile phones, radiofrequency fields, and health effects in children--epidemiological studies

In 2004, when WHO organized a workshop on children's sensitivity to electromagnetic fields, very few studies on radiofrequency fields were available. With the recent increase in mobile phone use among children and adolescents, WHO has identified studies on health effects in this age-group as a high priority research area. There are no empirical data supporting the notion that children and adolescents are more susceptible to RF exposure, but the number of studies is still relatively small. There are a few cross-sectional studies on well-being, cognitive effects and behavioral problems, and some cohort studies, mainly of maternal use of mobile phones during pregnancy. Cancer outcomes have been studied in relation to environmental RF exposure, e.g. from transmitters, and only one study on mobile phone use in children and adolescents and brain tumor risk has been published. Several methodological limitations need to be taken into consideration when interpreting the findings of the epidemiological studies. The cross-sectional design does not allow determination of the temporal sequence of exposure and outcome, and for several outcomes there is a large potential for reversed causality, i.e. that the outcome causes an increased RF exposure rather than the opposite. Biases such as recall errors in self-reported mobile phone use, lack of confounding control, e.g. of other aspects of mobile phone use than RF fields, trained behaviors, and pubertal development, makes causal interpretations impossible. Future studies need to include prospectively collected exposure information, incident outcomes, and proper confounding control. Monitoring of brain tumor incidence trends is strongly recommended.     

Cancer risk associated with the use of valsartan in Korea: A nationwide cohort study

BackgroundDespite valsartan’s widespread use, few studies have explored its potential carcinogenicity. We evaluated the association between valsartan and cancer.MethodsWe conducted a retrospective cohort study using data from 2002 to 2015 gathered from the National Health Insurance database. Patients with hypertension aged ≥ 30 who used valsartan or other angiotensin II receptor blockers (ARBs) were included. Eligible patients were those with no prior history of the use of any ARBs, diagnosis of cancer, or organ transplantation in the 4 years predating their first use of the drugs of interest. The primary and secondary outcomes included the occurrence of all cancers and site-specific solid cancers, respectively. After applying propensity score (PS) matching, Cox regression was used to calculate the hazard ratios (HRs) and 95 % confidence intervals (CIs).ResultsA total of 1,550,734 individuals were identified as new users of valsartan or other ARBs. Of the 153,047 valsartan users, 16,047 were diagnosed with cancer. No increased risk of overall cancer was observed in valsartan users as compared to other ARB users (aHR = 1.00; 95 % CI, 0.98–1.02). Valsartan was, however, associated with a slightly elevated risk of liver (aHR = 1.09; 95 % CI, 1.01–1.16) and kidney cancer (aHR = 1.11; 95 % CI, 1.02–1.22).ConclusionCompared with other ARBs, valsartan did not increase the risk of overall cancer. A slightly increased risk for some solid cancers was associated with valsartan use, though the absolute rate difference was small.