Johanna Mäkelä

Tandem mass spectrometric analysis of human milk triacylglycerols from normal weight and overweight mothers on different diets.

The composition and structures of TAGs in the human milk from mothers with different food choices and prepregnancy body mass index were determined with two tandem mass spectrometric methods (negative APCI-MS/MS and positive UHPLC/ESI-MS/MS) at the infants age of three months. The normal weight mothers with recommended food choices had more 18:3n-3 and less 18:0 in their milk than normal weight mothers with non-recommended food choices. A significant difference between the normal weight mothers on the non-recommended food choices and the other groups was seen in acyl carbon number: number of double bond (ACN:DB)-groups 54:6, 54:5, 54:3 and 54:2. In ACN:DB 52:7 and 52:6 the two recommended food choices-groups differed significantly from the two non-recommended food choices-groups. The regioisomerism of TAGs varied little despite differences in mothers weight and diet with sn-18:1-16:0-18:1 as the most prevalent regioisomer in the milk (13.8±2.7%). The results of this study highlight the importance of structure specific human milk substitutes and the careful selection of the MS/MS methods for analysis of mixtures of several isobaric TAGs.

Prediction of Adulthood Obesity Using Genetic and Childhood Clinical Risk Factors in the Cardiovascular Risk in Young Finns StudyCLINICAL PERSPECTIVE

Background— Obesity is a known risk factor for cardiovascular disease. Early prediction of obesity is essential for prevention. The aim of this study is to assess the use of childhood clinical factors and the genetic risk factors in predicting adulthood obesity using machine learning methods. Methods and Results— A total of 2262 participants from the Cardiovascular Risk in YFS (Young Finns Study) were followed up from childhood (age 3–18 years) to adulthood for 31 years. The data were divided into training (n=1625) and validation (n=637) set. The effect of known genetic risk factors (97 single-nucleotide polymorphisms) was investigated as a weighted genetic risk score of all 97 single-nucleotide polymorphisms (WGRS97) or a subset of 19 most significant single-nucleotide polymorphisms (WGRS19) using boosting machine learning technique. WGRS97 and WGRS19 were validated using external data (n=369) from BHS (Bogalusa Heart Study). WGRS19 improved the accuracy of predicting adulthood obesity in training (area under the curve [AUC=0.787 versus AUC=0.744, P<0.0001) and validation data (AUC=0.769 versus AUC=0.747, P=0.026). WGRS97 improved the accuracy in training (AUC=0.782 versus AUC=0.744, P<0.0001) but not in validation data (AUC=0.749 versus AUC=0.747, P=0.785). Higher WGRS19 associated with higher body mass index at 9 years and WGRS97 at 6 years. Replication in BHS confirmed our findings that WGRS19 and WGRS97 are associated with body mass index. Conclusions— WGRS19 improves prediction of adulthood obesity. Predictive accuracy is highest among young children (3–6 years), whereas among older children (9–18 years) the risk can be identified using childhood clinical factors. The model is helpful in screening children with high risk of developing obesity.

Hyperglycemia and lower diet quality in pregnant overweight women and increased infant size at birth and at 13 months of age — STEPS study

AIMS To study whether maternal overweight and/or hyperglycemia combined with life-style factors in healthy women predisposes to adverse pregnancy or infant health outcomes, such as differences in growth. METHODS At 26-28 weeks of gestation 82 overweight pregnant women (prepregnancy BMI ≥ 25 kg/m(2)) and 67 normal weight pregnant women (prepregnancy BMI<25 kg/m(2)) participating to STEPS study attended 2-hour oral glucose tolerance test (OGTT) with measurement of plasma glucose and insulin and calculation of HOMA, QUICKI and Matsuda ISI indices. Birth weights and lengths were obtained from hospital records and weights and heights at 13 months from study visits. Maternal physical activity and diet quality were studied with questionnaires. RESULTS Glucose concentrations were higher in overweight non-diabetic women (0 h=4.9, 1h=7.7, 2h=6.2 mmol/l, n=80) than normal weight women (0 h=4.5, 1h=6.8, 2h=5.6 mmol/l, all P<0.05, n=66) as were insulin concentrations at baseline (12.3 vs. 9.0 mU/l, P<0.05), but not later (1h=88.1 vs. 72.8 mU/l; 2h=63.5 vs. 55.5 mU/l, both P>0.05). Insulin resistance was higher and sensitivity lower (P<0.05 for all) in overweight than in normal weight women. The offspring of overweight mothers were 273 g heavier at birth and 700 g heavier at 13 months of age than the offspring of normal weight women (P<0.001). Normal weight women had preferable diet quality (P=0.023). No differences were seen in self-reported physical activity between overweight and normal weight women. CONCLUSIONS Maternal prepregnancy overweight increases risk of hyperglycemia in late-pregnancy and increased infant size at birth and 13 months possibly predisposing the infant to health risks later in life.

Genetic risk clustering increases children's body weight at 2 years of age – the STEPS Study

Genetic determinants have an impact on adult weight but the association between genetic determinants and weight at young age is still poorly understood.

End-of-life chemotherapy use at a Finnish university hospital: a retrospective cohort study

Abstract Background: Recent trends in the end-of-life (EOL) cancer care have suggested that the levels of treatment are becoming more aggressive. The aim of this single-center study was to evaluate the time from the last intravenous (IV) chemotherapy treatment to death and identify factors correlating with treatment closer to death. Material and methods: The study included all patients diagnosed with cancer at Turku University Central Hospital between the years 2005 and 2013 (N = 38,982) who received IV chemotherapy during the last year of life (N = 3285). The cohort of patients and their respective clinical information were identified from electronic medical records. Statistical analysis was performed to assess and compare the treatment strategies, taking into account the patient’s age, the year they were treated, and the type of cancer they were diagnosed with. Results: A total of 11,250 cancer patients died during the observation time and one-third (N = 3285, 29.2%) of them had received IV chemotherapy during the last year of life. The time from the last IV chemotherapy regimen to death remained consistent across the follow-up time. During the last month of life, every third patient under the age of 50 years and only one-tenth of patients over the age of 80 years received IV chemotherapy. Hematological malignancies and lymphomas were treated closer to death when compared to other diagnostic groups. Conclusions: During the period of 9 years, the pattern of EOL IV chemotherapy treatment remained stable. Every third patient died at tertiary care. Only 7.2% of patients who received IV chemotherapy during the last year of life were treated 14 days before death, which is in line with international recommendations. However, significant variation in EOL treatment strategies between different diagnosis and age groups were identified.

Assessing the utilization of radiotherapy near end of life at a Finnish University Hospital: a retrospective cohort study

Abstract Background: Palliative radiotherapy can improve quality of life for cancer patients during the last months of life. However, very short life expectancy may devastate the benefit of the treatment. This single center study assesses the utilization of radiotherapy during the last weeks of life. Material and methods: All cancer patients (N = 38,982) treated with radiotherapy (N = 11,395) in Turku University Central Hospital during 2005–2013 were identified in the database consisting of electronic patient records. One fourth (N = 2904, 25.5%) of the radiotherapy treatments were given during the last year of life. The last radiotherapy treatments and the time from the last radiotherapy treatment to death were assessed in regards to patients’ age, cancer diagnosis, domicile, place of death and the treatment year. Treatments given during the last two weeks of life were also assessed regarding the goal of treatment and the reason for possible discontinuation. Results: The median time from the last fraction of radiotherapy to death was 84 d. During the last two weeks before death (N = 340), pain (29.4%) was the most common indication for radiotherapy. Treatment was discontinued in 40.6% of the patients during the last two weeks of life, and worsening of general condition was the most common reason for discontinuity (70.3%). The patients receiving radiotherapy during the last weeks of life were more likely to die in tertiary care unit. During the last year of life single-fraction treatment was used only in 7% of all therapy courses. There was a statistically significant (p < .05) decrease in the median number of fractions in the last radiotherapy treatment between 2005–2007 (8 fractions) and 2011–2013 (6 fractions). Conclusions: Up to 70% of the treatments during the last two weeks of life were not delivered to alleviate pain and utilization of single fraction radiotherapy during the last year of life was infrequent. These observations suggest that practice of radiotherapy during the last weeks of life should be revisited.