This paper describes the methods used in the International Cancer Benchmarking Partnership Module 4 Survey (ICBPM4) which examines time intervals and routes to cancer diagnosis in 10 jurisdictions. We present the study design with defining and measuring time intervals, identifying patients with cancer, questionnaire development, data management and analyses.
Recruitment of participants to the ICBPM4 survey is based on cancer registries in each jurisdiction. Questionnaires draw on previous instruments and have been through a process of cognitive testing and piloting in three jurisdictions followed by standardised translation and adaptation. Data analysis focuses on comparing differences in time intervals and routes to diagnosis in the jurisdictions.
Our target is 200 patients with symptomatic breast, lung, colorectal and ovarian cancer in each jurisdiction. Patients are approached directly or via their primary care physician (PCP). Patients' PCPs and cancer treatment specialists (CTSs) are surveyed, and 'data rules' are applied to combine and reconcile conflicting information. Where CTS information is unavailable, audit information is sought from treatment records and databases.
Reliability testing of the patient questionnaire showed that agreement was complete (?=1) in four items and substantial (?=0.8, 95% CI 0.333 to 1) in one item. The identification of eligible patients is sufficient to meet the targets for breast, lung and colorectal cancer. Initial patient and PCP survey response rates from the UK and Sweden are comparable with similar published surveys. Data collection was completed in early 2016 for all cancer types.
An international questionnaire-based survey of patients with cancer, PCPs and CTSs has been developed and launched in 10 jurisdictions. ICBPM4 will help to further understand international differences in cancer survival by comparing time intervals and routes to cancer diagnosis.
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Evidence on alcohol consumption as a risk factor for dementia usually relates to overall consumption. The role of alcohol-induced loss of consciousness is uncertain.
To examine the risk of future dementia associated with overall alcohol consumption and alcohol-induced loss of consciousness in a population of current drinkers.
Seven cohort studies from the UK, France, Sweden, and Finland (IPD-Work consortium) including 131?415 participants were examined. At baseline (1986-2012), participants were aged 18 to 77 years, reported alcohol consumption, and were free of diagnosed dementia. Dementia was examined during a mean follow-up of 14.4 years (range, 12.3-30.1). Data analysis was conducted from November 17, 2019, to May 23, 2020.
Self-reported overall consumption and loss of consciousness due to alcohol consumption were assessed at baseline. Two thresholds were used to define heavy overall consumption: greater than 14 units (U) (UK definition) and greater than 21 U (US definition) per week.
Dementia and alcohol-related disorders to 2016 were ascertained from linked electronic health records.
Of the 131?415 participants (mean [SD] age, 43.0 [10.4] years; 80?344 [61.1%] women), 1081 individuals (0.8%) developed dementia. After adjustment for potential confounders, the hazard ratio (HR) was 1.16 (95% CI, 0.98-1.37) for consuming greater than 14 vs 1 to 14 U of alcohol per week and 1.22 (95% CI, 1.01-1.48) for greater than 21 vs 1 to 21 U/wk. Of the 96?591 participants with data on loss of consciousness, 10?004 individuals (10.4%) reported having lost consciousness due to alcohol consumption in the past 12 months. The association between loss of consciousness and dementia was observed in men (HR, 2.86; 95% CI, 1.77-4.63) and women (HR, 2.09; 95% CI, 1.34-3.25) during the first 10 years of follow-up (HR, 2.72; 95% CI, 1.78-4.15), after excluding the first 10 years of follow-up (HR, 1.86; 95% CI, 1.16-2.99), and for early-onset (
To investigate the shape of the causal relation between body mass index (BMI) and mortality.
Linear and non-linear mendelian randomisation analyses.
Nord-Trøndelag Health (HUNT) Study (Norway) and UK Biobank (United Kingdom).
Middle to early late aged participants of European descent: 56?150 from the HUNT Study and 366?385 from UK Biobank.
All cause and cause specific (cardiovascular, cancer, and non-cardiovascular non-cancer) mortality.
12?015 and 10?344 participants died during a median of 18.5 and 7.0 years of follow-up in the HUNT Study and UK Biobank, respectively. Linear mendelian randomisation analyses indicated an overall positive association between genetically predicted BMI and the risk of all cause mortality. An increase of 1 unit in genetically predicted BMI led to a 5% (95% confidence interval 1% to 8%) higher risk of mortality in overweight participants (BMI 25.0-29.9) and a 9% (4% to 14%) higher risk of mortality in obese participants (BMI =30.0) but a 34% (16% to 48%) lower risk in underweight (BMI
Study carcinogenicity of inorganic lead, classified as 'probably carcinogenic' to humans by the International Agency for Research on Cancer (brain, lung, kidney and stomach).
We conducted internal and external analyses for cancer incidence in two cohorts of 29?874 lead-exposed workers with past blood lead data (Finland, n=20?752, Great Britain=9122), with 6790 incident cancers. Exposure was maximum measured blood lead.
The combined cohort had a median maximum blood lead of 29?µg/dL, a mean first blood lead test of 1977, and was 87% male. Significant (p40?µg/dL) showed a significant excess for lung cancer in both countries combined, and significant excesses in Finland for brain and lung cancer. The Great Britain data were limited by small numbers for some cancers, and limited variation in exposure.
We found strong positive incidence trends with increasing blood lead level, for several outcomes in internal analysis. Two of these, lung and brain cancer, were sites of a priori interest.
Increased cancer risks have been reported among workers in the rubber manufacturing industry employed before the 1960s, but it is unclear for workers hired subsequently. The present study focused on cancer incidence among rubber workers first employed after 1975 in Sweden and the UK.
Two cohorts of rubber workers employed for at least 1 year were analysed. Standardised incidence ratios (SIRs), based on country-specific and period-specific incidence rates, were analysed for all cancers combined (except non-melanoma skin), bladder, lung, stomach cancer, leukaemia, non-Hodgkin's lymphoma and multiple myeloma. Exploratory analyses were conducted for other cancers with a minimum of 10 cases in both genders combined.
16 026 individuals (12 441 men; 3585 women) contributed to 397 975 person-years of observation, with 846 cancers observed overall (437 in the UK, 409 in Sweden). No statistically significant increased risk was observed for any site of cancer. A reduced risk was evident for all cancers combined (SIR=0.83, 95% CI (0.74 to 0.92)), lung cancer (SIR=0.74, 95% CI (0.59 to 0.93)), non-Hodgkin's lymphoma (SIR=0.67, 95% CI (0.45 to 1.00)) and prostate cancer (SIR=0.77, 95% CI (0.64 to 0.92)). For stomach cancer and multiple myeloma, SIRs were 0.93 (95% CI (0.61 to 1.43)) and 0.92 (95% CI 0.44 to 1.91), respectively. No increased risk of bladder cancer was observed (SIR=0.88, 95% CI (0.61 to 1.28)).
No significantly increased risk of cancer incidence was observed in the combined cohort of rubber workers first employed since 1975. Continued surveillance of the present cohorts is required to confirm absence of long-term risk and confirmatory findings from other cohorts would be important.
Socioeconomic differences in smoking over time and across national contexts are poorly understood. We assessed the magnitude of relative and absolute social class differences in smoking in cohorts from Britain, Finland, and Japan over 5-7 years.
The British Whitehall II study (n = 4350), Finnish Helsinki Health Study (n = 6328), and Japanese Civil Servants Study (n = 1993) all included employed men and women aged 35-68 at baseline in 1997-2002. Follow-up was in 2003-2007 (mean follow-up 5.1, 6.5, and 3.6 years, respectively). Occupational social class (managers, professionals and clerical employees) was measured at baseline. Current smoking and covariates (age, marital status, body mass index, and self-rated health) were measured at baseline and follow-up. We assessed relative social class differences using the Relative Index of Inequality and absolute differences using the Slope Index of Inequality.
Social class differences in smoking were found in Britain and Finland, but not in Japan. Age-adjusted relative differences at baseline ranged from Relative Index of Inequality 3.08 (95% confidence interval 1.99-4.78) among Finnish men to 2.32 (1.24-4.32) among British women, with differences at follow-up greater by 8%-58%. Absolute differences remained stable and varied from Slope Index of Inequality 0.27 (0.15-0.40) among Finnish men to 0.10 (0.03-0.16) among British women. Further adjustment for covariates had modest effects on inequality indices.
Large social class differences in smoking persisted among British and Finnish men and women, with widening tendencies in relative differences over time. No differences could be confirmed among Japanese men or women.
Changes over time in social class differences in smoking are poorly understood across countries. Our study focused on employees from Britain, Finland and Japan, and found relative and absolute and class differences among British and Finnish men and women. Key covariates had modest effects on the differences. Relative differences tended to widen over the 4- to 7-year follow-up, whereas absolute differences remained stable. In contrast, class differences in smoking among Japanese men or women were not found. Britain and Finland are at the late stage of the smoking epidemic model, whereas Japan may not follow the same model.
Cites: J Public Health (Oxf). 2012 Aug;34(3):390-622375070
To describe the characteristics of new users of cilostazol in Europe with the aim to support the evaluation of its benefit/risk as used in regular clinical practice before the implementation of labeling changes recommended by the European Medicines Agency.
New users of cilostazol were identified in populations enrolled in five European health automated databases in the UK (The Health Improvement Network [THIN]), Spain (EpiChron cohort and Information System for the Improvement of Research in Primary Care [SIDIAP]), Sweden (National Registers), and Germany (German Pharmacoepidemiological Research Database [GePaRD]) between 2002 and 2012. New users were characterized according to the prevalence of cardiovascular disease and other comorbidities, concurrent use of interacting medications, new contraindications, duration of use, and potential off-label prescribing.
We identified 22 593 new users of cilostazol. The median age was between 68.0 (THIN) and 73.7 (Sweden) years. More than 78% of users had concomitant cardiovascular disease, and between 78.8% (GePaRD) and 91.6% (THIN) were treated with interacting medications. Prevalence of new cardiovascular contraindications ranged from 1.5% (THIN) to 11.6% (GePaRD), and concurrent use of two or more antiplatelet drugs ranged from 6.3% (SIDIAP) to 13.5% (EpiChron cohort). Between 39.4% (Sweden) and 52.9% (THIN) of users discontinued cilostazol in the first 3 months. Between 41.0% (SIDIAP) and 93.4% (THIN) were considered to have received cilostazol according to the European Medicines Agency labeling.
Prosthetic implants used in total hip replacements (THR) have a range of bearing surface combinations (metal-on-polyethylene, ceramic-on-polyethylene, ceramic-on-ceramic, and metal-on-metal), head sizes (small [
To gain information on hair loss amongst curly coated retrievers by questionnaire and to define the clinical and pathological features of hair coat abnormalities in affected dogs in the United Kingdom and Sweden.
Questionnaires were completed by members of the Curly Coated Retriever Clubs. Fourteen dogs (six in the United Kingdom, eight in Sweden) were clinically examined and skin/hair samples collected for microscopy and histopathology. Blood was collected for haematological, biochemical and endocrine assays.
Of 90 dogs surveyed, 39 had current or previous episodes of symmetrical, non-pruritic alopecia and or frizzy coat changes, usually affecting caudal thighs, axillae, dorsum and neck before 18 months of age; 23 dogs had a waxing/waning course. Examined dogs generally matched the pattern described in questionnaires. Hair shaft anomalies comprised occasional distorted anagen bulbs (10 dogs) and transverse fractures (8 dogs). Vertical histopathological sections showed infundibular hyperkeratosis (28 of 30 sections) and low-grade pigment clumping (17 of 30). Subtle telogenisation of hair follicles was unequivocally confirmed by transverse histomorphometric analyses.
The follicular dysplasia of curly coated retriever reported here is similar to that of Irish water spaniels and Chesapeake Bay retrievers but distinct from that of Portuguese water dogs. The genetic basis requires further assessment.
Psychoses, especially schizophrenia, are often preceded by cognitive deficits and psychosis risk states. Altered metabolic profiles have been found in schizophrenia. However, the associations between metabolic profiles and poorer cognitive performance and psychosis risk in the population remain to be determined.
Detailed molecular profiles were measured for up to 8976 individuals from two general population-based prospective birth cohorts: the Northern Finland Birth Cohort 1986 (NFBC 1986) and the Avon Longitudinal Study of Parents and Children (ALSPAC). A high-throughput nuclear magnetic resonance spectroscopy platform was used to quantify 70 metabolic measures at age 15-16 years in the NFBC 1986 and at ages 15 and 17 years in ALSPAC. Psychosis risk was assessed using the PROD-screen questionnaire at age 15-16 years in the NFBC 1986 or the psychotic-like symptoms assessment at age 17 years in ALSPAC. Cognitive measures included academic performance at age 16 years in both cohorts and general intelligence and executive function in ALSPAC. Logistic regression measured cross-sectional and longitudinal associations between metabolic measures and psychosis risk and cognitive performance, controlling for important covariates.
Seven metabolic measures, primarily fatty acid (FA) measures, showed cross-sectional associations with general cognitive performance, four across both cohorts (low density lipoprotein diameter, monounsaturated FA ratio, omega-3 ratio and docosahexaenoic acid ratio), even after controlling for important mental and physical health covariates. Psychosis risk showed minimal metabolic associations.
FA ratios may be important in marking risk for cognitive deficits in adolescence. Further research is needed to clarify whether these biomarkers could be causal and thereby possible targets for intervention.