Aetiological Research Research Articles

Compensatory Hypertrophy in Paediatric Patients with a Unilateral Ureteropelvic Junction Obstruction

BackgroundCompensatory hypertrophy is common in children with solitary functioning kidney, but it is unknown whether it also develops in children with unilateral partial reduction of kidney function. ObjectiveThe aim of this study was to assess whether children with a unilateral ureteropelvic junction obstruction (UPJO) show compensatory growth of the unaffected kidney. Furthermore, we investigated whether the length of the unaffected kidney was related to the degree of split kidney function lost and other possible risk factors. Lastly, we studied a possible relationship with signs of kidney injury. Design, setting, and participantsWe retrospectively analysed clinical information from 194 children with a unilateral UPJO who participated in the Aetiologic research into Genetic and Occupational/environmental Risk factors for Anomalies in children (AGORA) data- and biobank. Data on kidney length, split kidney function, and other factors possibly associated with kidney length were extracted from electronic patient records. Outcome measurements and statistical analysisPearson’s correlation coefficients between the split kidney function and unaffected kidney length were calculated. Multivariable logistic regression analyses were performed to identify factors associated with kidney length and signs of kidney injury. Results and limitationsMost children with a UPJO had an unaffected kidney length above the reference for age at the end of follow-up (median age 6.5 yr). A correlation with split kidney function was present only in children with a split kidney function of ≥60% in the unaffected kidney (r = 0.41). Aside from split kidney function, UPJO side was the only determinant of kidney length, while no associations between kidney length and kidney injury were identified. ConclusionsCompensatory growth was visible in most children with a UPJO after sufficient follow-up time and was correlated with split kidney function in children with a severe UPJO. Contralateral kidney length provided no clear prognostic value for developing kidney injury. Studies with more patients and additional biomarkers of kidney injury are needed to further personalise care. Patient summaryChildren with obstruction of urine outflow in one kidney often had a larger contralateral kidney. However, the size of this kidney could not be used to predict which children would develop kidney injury.

Incidence and trends of ophthalmic cancer in Singapore: Data from Singapore Cancer Registry

Limited data are available on the incidence of primary ophthalmic cancers worldwide. We describe the incidence and trends of primary ophthalmic cancers in Singapore. Data on ophthalmic cancers diagnosed in Singapore from 1996 to 2016 were retrieved from the Singapore Cancer Registry for analysis. All were histologically proven primary ophthalmic cancers. Calculations of incidence and age-specific frequency of ophthalmic malignancy were made. A total of 297 cases were included, with males constituting 59.9%. The race distribution was 78.5% Chinese, 16.5% Malay, 3.7% Indians and 1.3% others. There was an overall increase in ophthalmic malignancies. The mean age of onset was 47.4 years. The most common cancers were retinoblastoma (93.3%) in patients younger than 15 years, and lymphoma (71.3%) in patients aged 15 years and older. There has been an increase in lymphomas from 16.7% in 1968-1995 to 71.3% in 1996-2016 in those aged 15 years and older. The most common types of ophthalmic cancer according to location are lymphoma of the orbit, conjunctiva, cornea and lacrimal gland; retinoblastoma of the retina; and malignant melanoma of the choroid and ciliary body. Our study reported the incidence and trends of ophthalmic cancer in the Singapore population and showed an overall increase in ophthalmic malignancies in Singapore from 1996-2016. A substantial increase in lymphomas over the last 2 decades was noted. The data could aid clinicians, epidemiologists and policymakers in implementing strategies to address trends in ophthalmic cancers and spur aetiological research to improve quality of life in patients with such cancers.

Cancers emerging early in adulthood: Analysis of trends and patterns in European cancer registries.

Although cancer is typically a disease of the older age groups, some types start emerging early in adulthood. This implies that exposures and stressors occurring before adulthood might play a role in the risk of cancer in adults. Little research has been conducted in this area. We used European data from the Cancer in Five Continents Vol. XI to calculate cumulative risks by the end of subsequent adulthood decades of age (20-29, 30-39, 40-49) for 34 cancer sites and classified them as early-age emerging cancers if they reached 0.005% by 29 years old, intermediate-age emerging cancers by 39 years old, and late-age emerging cancers after 40 years old. We used data from Cancer in Five Continents Plus to analyse time trends in incidence rates by age groups over the period 1998-2012. We identified 14 early-age emerging cancers. Nine of them showed significant increasing trends over calendar time in the early decades of adulthood, often more pronouncedly so in 20-29-year-olds than in 30-39 or 40-49-year-olds. The increase of colon cancer rates in the 20-29-year-olds was particularly high with an average annual percent change of 7.9% (95% confidence interval: 5.9%-10%). Decreases in incidence rates were only observed for cancer types classified as intermediate- or late-age emerging cancers. Cancer prevention efforts seem to have favourably impacted intermediate- and late-age emerging cancer incidence rates. For early-age emerging cancers, aetiological research is needed to identify exposures and stressors occurring early in life, especially for those cancers that have been increasing in young adults. This knowledge will be essential to develop preventive strategies.

Occipital neuralgia reavealing an atlantoaxial subluxation in an ankylosing spondylitis patient

Occipital neuralgia is a peripheral neuropathy of the neck and head characterized by unilateral paroxysmal headache of cervical origin, caused mostly by irritation or of the posterior large occipital nerve. We report the case of a patient with known history of axial and peripheral spondyloarthritis presenting with an unremitting right sided headache evolving for 2 months before examination. The Aetiological research revealed an atlantoaxial subluxation combining vertical and rotatory movements. The patient was surgically treated with C1/C2 laminectomy, an enlargement of the magnum canal and an occipito cervical arthrodesis reinforced posteriorly by a bone graft. While anterior atloaxoidal subluxation has been widely described in spondyloarthritis especially peripheral ones, vertical and rotatory subluxation has been rare to be seen especially when revealed by an occipital neuralgia.

A framework for studying risk factors for lower extremity musculoskeletal discomfort in nurses

Lower extremity musculoskeletal discomfort (MSD) is prevalent, but understudied, in nurses. A comprehensive, theoretical, aetiological model of lower extremity work-related MSD in hospital in-patient staff nurses was developed through a review of the literature to provide a framework for aetiological and intervention research. The framework informed the design of a survey of 502 hospital staff nurses. Symptom prevalence ranged from 32% in hip/thigh to 59% in ankle/foot regions. Logistic regression modelling using survey data showed that different work and personal factors were associated with discomfort in different regions of the lower extremity. Individual factors (e.g. older age, higher BMI or having any foot condition), physical factors (e.g. higher frequency of patient handling), psychosocial factors (e.g. lower job satisfaction) were associated with discomfort in one or more parts of the lower extremity. Future research should target these factors for intervention, to attempt to reduce occurrence of lower extremity discomfort in nurses. Practitioner Summary: Practitioners may find useful the illustrated, theoretical aetiological model of factors that could influence the prevalence of lower extremity discomfort in nurses. The model could guide conversations with nurses and observational analyses of nursing work. The model and survey results may provide ideas for intervention exploration. Abbreviations: MSD: musculoskeletal discomfort; BMI: body mass index; MSK: musculoskeletal; ICU: intensive care unit; NLERF: nurses' lower extremity MSD risk factor; NASA-TLX: NASA-task load index

Innovations in applied decision theory for health and safety

ObjectivesThere are established methods for occupational epidemiological cohort analysis, such as proportional hazards regression, that are well suited to aetiological research and yield parameter estimates that allow for succinct communication...

Why evidence still matters to general practice: James Mackenzie Lecture 2019.

When Sir James Mackenzie moved back from London to St Andrews to establish the Institute of Clinical Research in 1919, he was given an opportunity to reflect on his research and explain why a clinical research institute was needed. In his address delivered at the opening of the Institute and in other publications,1,2 Mackenzie outlined the simultaneous importance of clinical observation: building an evidence base for diagnosis, prognosis, and therapeutic advances; and establishing a systematic approach to clinical care. In this Mackenzie Lecture, I hope to draw parallels between these observations of Mackenzie with the ongoing importance of evidence to the clinical care of patients in primary care in the 21st century. My aim is to illustrate why evidence still matters to clinical general practice using examples that address the domains of diagnosis and prognosis, as well as a critical examination of the risks and benefits of drug therapy. Though these examples are contemporary, Mackenzie’s observations in relation to the clinical and methodological issues are prescient and relevant to 21st-century clinical practice. Mackenzie understood that researchers should be clear in both their research question and the methods they employ to carry out research, saying ‘those engaged in medical research should pause and consider what they are doing … and be certain that their methods are suited to their purpose’ . In this observation, Mackenzie showed considerable foresight in relation to the significant methodological and analytical advances in research methods that have occurred since his time.3 Most particularly there has been the establishment of evidence-based medicine (EBM) in the application of clinical epidemiology to patient care.4 These methodological considerations by Mackenzie are the forerunner in relation to the array of study designs that address important clinical domains in relation to aetiological, diagnostic, prognostic, and therapeutic research. …

Pathology-confirmed versus non pathology-confirmed cancer diagnoses: incidence, participant characteristics, and survival

Cancer diagnoses which are not confirmed by pathology are often under-registered in cancer registries compared to pathology-confirmed diagnoses. It is unknown how many patients have a non pathology-confirmed cancer diagnosis, and whether their characteristics and survival differ from patients with a pathology-confirmed diagnosis. Participants from the prospective population-based Rotterdam Study were followed between 1989 and 2013 for the diagnosis of cancer. Cancer diagnoses were classified into pathology-confirmed versus non pathology-confirmed (i.e., based on imaging or tumour markers). We compared participant characteristics and the distribution of cancers at different sites. Furthermore, we investigated differences in overall survival using survival curves adjusted for age and sex. During a median (interquartile range) follow-up of 10.7 (6.3–15.9) years, 2698 out of 14,024 participants were diagnosed with cancer, of which 316 diagnoses (11.7%) were non pathology-confirmed. Participants with non pathology-confirmed diagnoses were older, more often women, and had a lower education. Most frequently non pathology-confirmed cancer sites included central nervous system (66.7%), hepato-pancreato-biliary (44.5%), and unknown primary origin (31.2%). Survival of participants with non pathology-confirmed diagnoses after 1 year was lower compared to survival of participants with pathology-confirmed diagnoses (32.6% vs. 63.4%; risk difference of 30.8% [95% CI 25.2%; 36.2%]). Pathological confirmation of cancer is related to participant characteristics and cancer site. Furthermore, participants with non pathology-confirmed diagnoses have worse survival than participants with pathology-confirmed diagnoses. Missing data on non pathology-confirmed diagnoses may result in underestimation of cancer incidence and in an overestimation of survival in cancer registries, and may introduce bias in aetiological research.

A Nationwide Study of Prevalence Rates and Characteristics of 199 Chronic Conditions in Denmark.

BackgroundReal-world data of disease prevalence represents an important but underutilised source of evidence for health economic modelling.AimsThe aim of this study was to estimate nationwide prevalence rates and summarise the characteristics of 199 chronic conditions using Danish population-based health registers, to provide an off-the-shelf tool for decision makers and researchers.MethodsThe study population comprised all Danish residents aged 16 years or above on 1 January 2013 (n = 4,555,439). The study was based on the linkage of national registers covering hospital contacts, contacts with primary care (including general practitioners) and filled-in out-of-hospital prescriptions.ResultsA total of 65.6% had one or more chronic condition. The ten conditions with the highest degree of prevalence were hypertension (23.3%), respiratory allergy (18.5%), disorders of lipoprotein metabolism (14.3%), depression (10.0%), bronchitis (9.2%), asthma (7.9%), type 2 diabetes (5.3%), chronic obstructive lung disease (4.7%), osteoarthritis of the knee (3.9%) and finally osteoporosis (3.5%) and ulcers (3.5%) in joint tenth place. Characteristics by gender, age and national geographical differences were also presented.ConclusionsA nationwide catalogue of the prevalence rates and characteristics of patients with chronic conditions based on a nationwide population is provided. The prevalence rates of the 199 conditions provide important information on the burden of disease for use in healthcare planning, as well as for economic, aetiological and other research.Electronic supplementary materialThe online version of this article (10.1007/s41669-019-0167-7) contains supplementary material, which is available to authorized users.

Review article: the incidence and risk factors for irritable bowel syndrome in population-based studies.

In the absence of prior gastrointestinal infection, the risk factors for irritable bowel syndrome (IBS) are not well established. To identify the incidence and risk factors for IBS in general population samples METHODS: Narrative review of population-based studies. Electronic databases were searched using the keywords "incidence," "onset," "epidemiology," "population," "risk factors" with "irritable bowel syndrome" with subsequent hand searching. Inclusion criteria were: population-based, adults, prospective design (including retrospective case cohorts), clinical or research diagnosis of IBS and exclusion of individuals who had IBS prior to recruitment. Of 1963 papers, 38 were included; all provided data on risk factors, 27 reported incidence. The median incidence of physician-diagnosed IBS in 19 general population cohorts was 38.5 per 10000 person-years (interquartile range=20-45.3). In 14 cohorts with specific medical disorders, median incidence was 92 per 10000 person-years (IQR: 73.9-119). Apart from gastroenteritis, the most common risk factors were other medical disorders, female sex, age (both young and old), anxiety and depression, life events/stress, frequent healthcare use, pain and sleep disorders. The results were conflicting for alcohol consumption, smoking and BMI. Incidence rates were similar in different countries but risk factors differed. Incidence rates were generally lower than previous estimates reflecting physician-diagnosed IBS. The results highlight the importance of other medical and psychosocial problems in the onset of IBS in addition to prior gastrointestinal infections. Aetiological research could be enhanced by studying the underlying mechanisms relating to all of these risk factors.

Associations between usual food intake and faecal sterols and bile acids: results from the Cooperative Health Research in the Augsburg Region (KORA FF4) study.

Animal sterols, plant sterols and bile acids in stool samples have been suggested as biomarkers of dietary intake. It is still unknown whether they also reflect long-term habitual dietary intake and can be used in aetiological research. In a subgroup of the Cooperative Health Research in the Augsburg Region (KORA FF4) study, habitual dietary intake was estimated based on repeated 24-h food list and a FFQ. Stool samples were collected according to a standard operating procedure and those meeting the quality criteria were extracted and analysed by means of a metabolomics technique. The present study is based on data from 513 men and 495 women with a mean age of 60 and 58 years, respectively, for which faecal animal and plant sterols and bile acids concentrations and dietary intake data were available. In adjusted regression models, the associations between food intake and log-normalised metabolite concentrations were analysed. Bonferroni correction was used to account for multiple testing. In this population-based sample, associations between habitual dietary intake and faecal concentrations of animal sterols were identified, while the impact of usual diet on bile acids was limited. A habitual diet high in 'fruits' and 'nuts and seeds' is associated with lower animal faecal sterols concentrations, whereas a diet high in 'meat and meat products' is positively related to faecal concentrations of animal sterols. A positive association between glycocholate and fruit consumption was found. Further studies are necessary for evaluation of faecal animal sterols as biomarkers of diet. The findings need to be confirmed in other populations with diverse dietary habits.

The International Childhood Cancer Cohort Consortium (I4C): A research platform of prospective cohorts for studying the aetiology of childhood cancers.

Childhood cancer is a rare but leading cause of morbidity and mortality. Established risk factors, accounting for <10% of incidence, have been identified primarily from case-control studies. However, recall, selection and other potential biases impact interpretations particularly, for modest associations. A consortium of pregnancy and birth cohorts (I4C) was established to utilise prospective, pre-diagnostic exposure assessments and biological samples. Eligibility criteria, follow-up methods and identification of paediatric cancer cases are described for cohorts currently participating or planning future participation. Also described are exposure assessments, harmonisation methods, biological samples potentially available for I4C research, the role of the I4C data and biospecimen coordinating centres and statistical approaches used in the pooled analyses. Currently, six cohorts recruited over six decades (1950s-2000s) contribute data on 388120 mother-child pairs. Nine new cohorts from seven countries are anticipated to contribute data on 627500 additional projected mother-child pairs within 5years. Harmonised data currently includes over 20 "core" variables, with notable variability in mother/child characteristics within and across cohorts, reflecting in part, secular changes in pregnancy and birth characteristics over the decades. The I4C is the first cohort consortium to have published findings on paediatric cancer using harmonised variables across six pregnancy/birth cohorts. Projected increases in sample size, expanding sources of exposure data (eg, linkages to environmental and administrative databases), incorporation of biological measures to clarify exposures and underlying molecular mechanisms and forthcoming joint efforts to complement case-control studies offer the potential for breakthroughs in paediatric cancer aetiologic research.

The mechanism of the preventive effect of Shen'an capsule on the calcium oxalate crystal-induced early renal injury based on metabolomics.

Kidney stone disease is a worldwide metabolism-associated disorder with a high incidence of renal dysfunction. However, effective methods to prevent crystalline nephropathy are still lacking owing to the absence of aetiological research. Shen'an (SA) capsules are prepared from Chinese medicinal compounds and are considered a promising treatment for the prevention of crystal-induced renal injury. In this study, 24 mice were randomly divided into four groups: saline, oxalate, SA-treated (via preventive administration) and SA-only groups. A metabolomics analysis based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to explore the plasma metabolic profiles among the different groups. The amount of crystal deposition and the decline in kidney function were significantly alleviated by the use of SA capsule. A total of 24 metabolites that showed a reversal trend following SA capsule administration were identified as plasma biomarkerss of the preventive effects of SA capsules on crystal-induced renal injury. Most of these metabolites were involved in the metabolisms of lipid metabolism, energy metabolism, glutathione metabolism and vitamin metabolism. In conclusion, SA capsules exert a preventive effect in mice with crystal-induced kidney injury via the regulation of multiple metabolic pathways.

Cancer epidemiology fieldwork in a resource-limited setting: Experience from the western Kenya ESCCAPE esophageal cancer case-control pilot study

BackgroundCase-control studies remain an important study design for aetiologic research on cancer, particularly when cohorts are not available. In addition to the potential biases inherent in this design, conducting fieldwork in settings with weak health care and information systems for cancer, such as in sub Saharan Africa, confer additional challenges which we present here with the aim to share experience to guide future studies. MethodsWe undertook a hospital-based case-control study of squamous cell esophageal cancer at the Moi Teaching and Referral Hospital in Eldoret, West Kenya. Cases were recruited at endoscopy and controls from hospital wards, age and gender frequency-matched to cases. Urine, toenails, blood and tumour biopsy were collected and a questionnaire administered. ResultsDuring this pilot phase, 143 cases and 155 controls were successfully recruited. Complete questionnaire data was obtained through e-data collection. Biospecimen collection was possible with support of an already existing equipped laboratory. We introduce changes made in the main study phase, including on expansion of the control groups to allow to consideration of selection bias. ConclusionsExtra attention and funding to train and monitor data quality and biospecimen collection and collaboration of a large group held together by strong leadership are essential. We recommend studies based on regional treatment centres with their more defined catchment areas rather than in the capital cities as referral routes in multi-level health care systems are severely attrition prone.

Neurostimulation in Clinical and Sub-clinical Eating Disorders: A Systematic Update of the Literature.

IntroductionWhilst psychological therapies are the main approach to treatment of eating disorders (EDs), advances in aetiological research suggest the need for the development of more targeted, brain-focused treatments. A range of neurostimulation approaches, most prominently repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS), are rapidly emerging as potential novel interventions. We have previously reviewed these techniques as potential treatments of EDs.AimTo provide an update of the literature examining the effects of DBS, rTMS and tDCS on eating behaviours, body weight and associated symptoms in people with EDs and relevant analogue populations.MethodsUsing PRISMA guidelines, we reviewed articles in PubMed, Web of Science, and PsycINFO from 1st January 2013 until 14th August 2017, to update our earlier search. Studies assessing the effects of neurostimulation techniques on eating and weight-related outcomes in people with EDs and relevant analogue populations were included. Data from both searches were combined.ResultsWe included a total of 32 studies (526 participants); of these, 18 were newly identified by our update search. Whilst findings are somewhat mixed for bulimia nervosa, neurostimulation techniques have shown potential in the treatment of other EDs, in terms of reduction of ED and associated symptoms. Studies exploring cognitive, neural, and hormonal correlates of these techniques are also beginning to appear.ConclusionsNeurostimulation approaches show promise as treatments for EDs. As yet, large well-conducted randomised controlled trials are lacking. More information is needed about treatment targets, stimulation parameters and mechanisms of action.

ETHNICITY, CARDIOVASCULAR DISEASE AND RISK OF DEMENTIA

South Asian and Black minority ethnic groups are known to have a higher incidence and prevalence of cardiovascular disease than White ethnic groups and this may in turn increase their risk of developing dementia, as well. This study seeks to explore this hypothesis using large scale population-based databases including the UK primary care- based Clinical Practice Research Datalink (CPRD), the Hospital Episode Statistics (HES) and the Office for National Statistics (ONS) mortality data. All eligible participants over the age of 50y from the CPRD database were included in this analysis and were stratified into 5 different ethnic groups, White, Black, South Asian, East Asian and Mixed and the outcome of interest was a dementia diagnosis. Dementia cases were sequentially added to the Electronic Health Record diagnoses, firstly using HES data, ONS mortality data and then supplementing these with algorithm-derived cases. Their trajectories were followed over the observation period 1995–2015, until death or dementia outcome. Information on cardiovascular Disease (CVD) and risk factor data of interest was also captured during this observation period. Cox regression was used to examine the association between ethnicity, CVD and risk factors and risk of dementia. Descriptive analyses showed that the overall prevalence and incidence rates for dementia over the last 2 decades have increased. Dementia prevalence rates in 1995 (2.09%), 2005 (2.28%) and 2015 (2.40%). Incidence rates in 1995 (0.02%), 2005 (0.14%) and 2015 (0.27%). From the dementia cohort of 326,355 cases; 188,805 (White), 2,094 (Black), 3662 (South Asian), 1,065 (East Asian) and 1491 (Mixed). The significance of ethnicity and risk factors in the development of dementia will be analysed and presented. Understanding the differences for ethnic variation in dementia rates is not only vital for aetiological research but also in the development of prevention strategies. This will be the first retrospective longitudinal study to be conducted on a large UK clinical database, to explore the effects of ethnicity on dementia risk.

Cancer subtypes in aetiological research.

Researchers often attempt to categorize tumors into more homogeneous subtypes to better predict prognosis or understand pathogenic mechanisms. In clinical research, typically the focus is on prognosis: the tumor subtypes are intended to be associated with specific responses to treatment and/or different clinical outcomes. In aetiological research, the focus is on identifying distinct pathogenic mechanisms, which may involve different risk factors. We used directed acyclic graphs to present a framework for considering potential biases arising in aetiological research of tumor subtypes, when there is incomplete correspondence between the identified subtypes and the underlying pathogenic mechanisms. We identified two main scenarios: (1) weak effect, when the tumor subtypes are identified through combinations of characteristics and some of these characteristics are affected by factors that are unrelated with the underlying pathogenic mechanisms; and (2) lack of causality, when the set of characteristics corresponds with a mechanism that is actually not a cause of the tumor of interest. Examples of the magnitude of bias that can be introduced in these situations are provided. Although categorization of tumors into homogenous subtypes may have important implications for aetiological research and identification of risk factors, the characteristics used to classify tumors into subtypes should be as close as possible to the actual pathogenic mechanisms to avoid interpretative biases. Whenever our knowledge of these mechanisms is limited, research into risk factors for tumor subtypes should first aim to causally link the characteristics to the pathogenic mechanisms.

International incidence of childhood cancer, 2001–10: a population-based registry study

SummaryBackgroundCancer is a major cause of death in children worldwide, and the recorded incidence tends to increase with time. Internationally comparable data on childhood cancer incidence in the past two decades are scarce. This study aimed to provide internationally comparable local data on the incidence of childhood cancer to promote research of causes and implementation of childhood cancer control.MethodsThis population-based registry study, devised by the International Agency for Research on Cancer in collaboration with the International Association of Cancer Registries, collected data on all malignancies and non-malignant neoplasms of the CNS diagnosed before age 20 years in populations covered by high-quality cancer registries with complete data for 2001–10. Incidence rates per million person-years for the 0–14 years and 0–19 years age groups were age-adjusted using the world standard population to provide age-standardised incidence rates (WSRs), using the age-specific incidence rates (ASR) for individual age groups (0–4 years, 5–9 years, 10–14 years, and 15–19 years). All rates were reported for 19 geographical areas or ethnicities by sex, age group, and cancer type. The regional WSRs for children aged 0–14 years were compared with comparable data obtained in the 1980s.FindingsOf 532 invited cancer registries, 153 registries from 62 countries, departments, and territories met quality standards, and contributed data for the entire decade of 2001–10. 385 509 incident cases in children aged 0–19 years occurring in 2·64 billion person-years were included. The overall WSR was 140·6 per million person-years in children aged 0–14 years (based on 284 649 cases), and the most common cancers were leukaemia (WSR 46·4), followed by CNS tumours (WSR 28·2), and lymphomas (WSR 15·2). In children aged 15–19 years (based on 100 860 cases), the ASR was 185·3 per million person-years, the most common being lymphomas (ASR 41·8) and the group of epithelial tumours and melanoma (ASR 39·5). Incidence varied considerably between and within the described regions, and by cancer type, sex, age, and racial and ethnic group. Since the 1980s, the global WSR of registered cancers in children aged 0–14 years has increased from 124·0 (95% CI 123·3–124·7) to 140·6 (140·1–141·1) per million person-years.InterpretationThis unique global source of childhood cancer incidence will be used for aetiological research and to inform public health policy, potentially contributing towards attaining several targets of the Sustainable Development Goals. The observed geographical, racial and ethnic, age, sex, and temporal variations require constant monitoring and research.FundingInternational Agency for Research on Cancer and the Union for International Cancer Control.

Prediction versus aetiology: common pitfalls and how to avoid them.

Prediction research is a distinct field of epidemiologic research, which should be clearly separated from aetiological research. Both prediction and aetiology make use of multivariable modelling, but the underlying research aim and interpretation of results are very different. Aetiology aims at uncovering the causal effect of a specific risk factor on an outcome, adjusting for confounding factors that are selected based on pre-existing knowledge of causal relations. In contrast, prediction aims at accurately predicting the risk of an outcome using multiple predictors collectively, where the final prediction model is usually based on statistically significant, but not necessarily causal, associations in the data at hand.In both scientific and clinical practice, however, the two are often confused, resulting in poor-quality publications with limited interpretability and applicability. A major problem is the frequently encountered aetiological interpretation of prediction results, where individual variables in a prediction model are attributed causal meaning. This article stresses the differences in use and interpretation of aetiological and prediction studies, and gives examples of common pitfalls.

The evaluation stage of the Hoeven Outcome Monitor (HOM): Towards an evidence based groundwork in forensic mental health

This study examined if a macro-, meso-, and micro outcome measurement instrument that constitutes the evaluation stage of a Dutch forensic psychiatric outcome monitor, the Hoeven Outcome Monitor (HOM), can provide a first step towards a more evidence based groundwork in forensic mental health. General, serious, very serious, special, and tbs meriting recidivism during treatment, after treatment, and overall were charted for forensic psychiatric patients discharged from a Dutch forensic psychiatric centre between 1999 and 2008 (N=164). Re-conviction data were obtained from the official Criminal Records System, and the mean follow-up time was 116.2months. First, the results showed that the macro-measurements provide comparative outcome measures to generate insight into the overall effectiveness of forensic psychiatric treatment. Second, the meso-measurements yielded clinically relevant treatment outcome data for all discharged patients to generate a complete view of treatment effectiveness. Finally, the micro-measurements allowed access to detailed patient and treatment effectiveness assessments that provides the empirical foundation to conduct aetiological research into the prediction and control of high-risk behaviour. Thus, an outcome measurement instrument in line with Evidence Based Medicine and best practice guidelines was designed that provides an empirically sound evaluation framework for treatment effectiveness, and an impetus for the development of effective interventions to generate an evidence based groundwork in forensic mental health.