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1.  Presenting symptoms of children with cancer: a primary-care population-based study 
The British Journal of General Practice  2012;62(600):e458-e465.
Background
Knowledge of how children with cancer present in general practice is sparse. Timely referral from general practice is important to ensure early diagnosis.
Aim
To investigate the presenting symptoms and GPs’ interpretations of symptoms of children with cancer.
Design and setting
A Danish nationwide population-based study including children (<15 years) with an incident cancer diagnosis (January 2007 to December 2010).
Method
A questionnaire on symptoms and their interpretation was mailed to GPs (n?=?363). Symptoms were classified according to the International Classification of Primary Care (ICPC)-2 classification.
Results
GPs’ response rate was 87% (315/363) and GPs were involved in the diagnostic process of 253 (80.3%) children. Symptoms were few (2.4 per child) and most fell into the category ‘general and unspecified’ (71.9%), apart from patients with tumours of the central nervous system (CNS), whose symptoms fell mostly in the category ‘neurological’ (for example, headache). Symptoms like pain, swelling/lump, or fatigue were reported in 25% of the patients and they were the most commonly reported symptoms. GPs interpreted children’s symptoms as alarm symptoms in 20.2%, as serious (that is, not alarm) symptoms in 52.9%, and as vague symptoms in 26.9%. GPs’ interpretation varied significantly by diagnosis (P<0.001).
Conclusion
Children with cancer presented with few symptoms in general practice, of which most were ‘general and unspecified’ symptoms. Only 20% presented alarm symptoms, while 27% presented vague and non-specific symptoms. This low level of alarm symptoms may influence the time from symptom presentation in general practice to final diagnosis.
doi:10.3399/bjgp12X652319
PMCID: PMC3381271  PMID: 22781993
childhood cancer; family practice; patients; signs; symptoms
2.  Use of Primary Care during the Year before Childhood Cancer Diagnosis: A Nationwide Population-Based Matched Comparative Study 
PLoS ONE  2013;8(3):e59098.
Objective
Childhood cancer is rare and symptoms tend to be unspecific and vague. Using the utilization of health care services as a proxy for symptoms, the present study seeks to determine when early symptoms of childhood cancer are seen in general practice.
Methods
A population-based matched comparative study was conducted using nationwide registry data. As cases, all children in Denmark below 16 years of age (N = 1,278) diagnosed with cancer (Jan 2002-Dec 2008) were included. As controls, 10 children per case matched on gender and date of birth (N = 12,780) were randomly selected. The utilization of primary health care services (daytime contacts, out-of-hours contacts and diagnostic procedures) during the year preceding diagnosis/index date was measured for cases and controls.
Results
During the six months before diagnosis, children with cancer used primary care more than the control cohort. This excess use grew consistently and steadily towards the time of diagnosis with an IRR = 3.19 (95%CI: 2.99–3.39) (p<0.0001) during the last three months before diagnosis. Children with Central Nervous System (CNS) tumours had more contacts than other children during the entire study period. The use of practice-based diagnostic tests and the number of out-of-hours contacts began to increase four to five months before cancer diagnosis.
Conclusions
The study shows that excess health care use, a proxy for symptoms of childhood cancer, occurs months before the diagnosis is established. Children with lymphoma, bone tumour or other solid tumours had higher consultation rates than the controls in the last five months before diagnosis, whereas children with CNS tumour had higher consultation rates in all twelve months before diagnosis. More knowledge about early symptoms and the diagnostic pathway for childhood cancer would be clinically relevant.
doi:10.1371/journal.pone.0059098
PMCID: PMC3595276  PMID: 23554980
3.  The 5-minute Apgar score as a predictor of childhood cancer: a population-based cohort study in five million children 
BMJ Open  2012;2(4):e001095.
Objective
The aetiology of childhood cancer remains largely unknown but recent research indicates that uterine environment plays an important role. We aimed to examine the association between the Apgar score at 5 min after birth and the risk of childhood cancer.
Design
Nationwide population-based cohort study.
Setting
Nationwide register data in Denmark and Sweden.
Study population
All live-born singletons born in Denmark from 1978 to 2006 (N=1 771 615) and in Sweden from 1973 to 2006 (N=3 319 573). Children were followed up from birth to 14 years of age.
Main outcome measures
Rates and HRs for all childhood cancers and for specific childhood cancers.
Results
A total of 8087 children received a cancer diagnosis (1.6 per 1000). Compared to children with a 5-min Apgar score of 9–10, children with a score of 0–5 had a 46% higher risk of cancer (adjusted HR 1.46, 95% CI 1.15 to 1.89). The potential effect of low Apgar score on overall cancer risk was mostly confined to children diagnosed before 6 months of age. Children with an Apgar score of 0–5 had higher risks for several specific childhood cancers including Wilms’ tumour (HR 4.33, 95% CI 2.42 to 7.73).
Conclusions
A low 5 min Apgar score was associated with a higher risk of childhood cancers diagnosed shortly after birth. Our data suggest that environmental factors operating before or during delivery may play a role on the development of several specific childhood cancers.
doi:10.1136/bmjopen-2012-001095
PMCID: PMC3425910  PMID: 22874628
Oncology; Epidemiology; Paediatric oncology; Preventive Medicine

Results 1-3 (3)