To Örebro University

Several polymorphic loci linked to lactase persistence (LP) have been described, all located in a small mutational hotspot region far upstream (approximate to 14kb) of the lactase (LCT) gene. One is typically found in Europeans, LCT -13910C>T, several others are found in East Africans and Arabs, e.g. LCT -13907C>G and LCT -13915T>G. The possibility of similar loci, specific to populations in South and Central America, has not received much attention so far. To identify possible novel polymorphisms in the mutational hotspot region, we sampled 158 subjects from a rural area in South-Central Mexico. DNA was isolated from serum, and Sanger sequencing of a 501bp region spanning the LCT -13910C>T hotspot was successfully performed in 150 samples. The frequency of the European-type LCT -13910T-allele was q=0.202, and 35% of the population was thus lactase-persistent (CT or TT). Sixteen novel genetic variants were found amongst 11 of the subjects, all were heterozygotes: seven of the subjects were also carriers of at least one LCT -13910T-allele. Thus, the mutational hotspot region is also a hotspot in the rural Mexican population: 11/150 subjects carried a total of 16 previously unknown private mutations but no novel polymorphism was found. The relationship between such novel genetic variants in Mexicans and lactase persistence is worthy of more investigation.

Background: According to the prevailing theory about the genetic background to lactose intolerance, there are three genotypes but only two adult physiological phenotypes: lactase persistence in individuals with the CT and TT genotypes and lactase non-persistence in individuals with the CC genotype. However, analysis of lactase activity from intestinal biopsies has revealed three distinct levels of activity, suggesting that an intermediate physiological phenotype may exist.

Aim: To assess possible disparities between different genotypes with regard to biomarkers of lactase activity and physical symptoms during an oral lactose load test.

Methods: A retrospective study using an oral lactose load test (n=487). Concentrations of hydrogen in exhaled air and blood glucose were measured. Afterwards, subjects were asked to provide oral mucosa samples for genotyping and answer a questionnaire (participation rate 56%, n=274).

Results: Mean hydrogen levels in exhaled air at 120min were significantly higher in the CT genotype than in the TT genotype. There was no significant difference in blood glucose levels between the two groups. Reported symptoms, with the possible exception of abdominal pain, were equally prevalent in both groups.

Conclusions: Subjects with the CT and TT genotypes, hitherto classified as lactase-persistent, differ in their physiological response to lactose intake, indicating differences in phenotype which could have clinical significance.

The delivery of efficient nonpharmacological treatment to prevent the loss of muscle mass in older adults is a major challenge, and information on the combined effects of training and diet is particularly important. Here we aimed to evaluate the effects of 24 wk of resistance training combined with a healthy dietary approach (n-6/n-3 ratio < 2) in a population of healthy and physically active older women (65-70 years). The three-armed randomized controlled trial included a resistance training + healthy diet group (RT-HD), a resistance training group (RT), and controls (CON). All subjects included in the study were physically active and had low levels of serum inflammatory markers. In accordance with the dietary goals, the n-6/n-3 ratio dietary intake significantly decreased only in RT-HD by 42%. An increase in 1 repetition maximum in leg extension occurred in RT (+20.4%) and RT-HD (+20.8%), but not in CON. Interestingly, leg lean mass significantly increased only in RT-HD (+1.8%). While there were no changes in serum C-reactive protein and IL-6 levels, a significant decrease in serum level of the pro-inflammatory precursor arachidonic acid (-5.3 +/- 9.4%) together with an increase in serum n-3 docosahexaenoic acid (+8.3%) occurred only in RT-HD. Altogether, this study demonstrates that the effects of resistance training on muscle mass in healthy older adults can be optimized by the adoption of a healthy diet.

Background: Overweight and obesity are growing public health problems in high income countries and is now growing at a dramatic pace in low and middle income countries, particularly in urban settings. The aim of this trial was to examine the effects of a weight reduction program in adults and to determine whether or not a more extensive intervention was superior to ordinary care.

Methods: Patients seeking advice for overweight/obesity or illness related to overweight/obesity at eight primary health care centers in Sweden were randomized either to intervention or control care groups with both groups given dietary advice and individualized information on increased regular physical activity. In the intervention group advice was more extensive and follow-up more frequent than in the control group during the study period of two years. Main outcome measure was reduction in body weight of five percent or more from study start.

Results: From October 2004 to April 2006, 133 patients, 67 in the intervention group and 66 in the control group, were randomized over a period of 18 months. Target weight was achieved at 12 months by 26.7% of the patients in the intervention group compared with 18.4% in the control group (p = 0.335). There was an average absolute weight loss of 2.5 kg in the intervention group and 0.8 kg in the control group at 12 months as compared with the weight at study entry. There were no significant differences between the groups in quality of life, blood glucose and lipids. At 24 months target weight was achieved in 21.9% versus 15.6%, with an average weight reduction of 1.9 kg and 1.2 kg in the two groups, respectively.

Conclusions: Promotion of a diet with limited energy intake, appropriate composition of food and increased physical activity had limited effects on body weight in a Swedish primary care setting. More extensive advice and more frequent visits made no significant difference to the outcome.

Objective: The aim of the study was to assess the effect on prescription quality and quality of life after intervention with prescription reviews and promotion of patient participation in primary care. Design. A randomized controlled study with three groups: (A) controls, (B) prescription review sent to physician, and (C) as in B and with a current comprehensive medication record sent to the patient. Setting. The municipality of Ö rebro, Sweden (130 000 inhabitants). Intervention. The study focused on the easiest possible intervention to increase prescription quality and thereby increase quality of life. The intervention should be cost-effi cient, focus on colleague-to-colleague advice, and be possible to perform in the primary health care centre without additional resources such as a pharmacist.

Subjects: 150 patients recently discharged from hospital. Inclusion criteria were: 75 years, fi ve drugs and living in ordinary homes. Main outcome measures. Quality of life (EQ-5D index, EQ VAS) and quality of prescriptions.

Results: Extreme polypharmacy was common and persistent in all three groups and this was accompanied by an unchanged frequency of drug-risk indicators. There was a low EQ-5D index and EQ VAS in all three groups throughout the study. No statistically signifi cant differences were found anywhere between the groups.

Conclusion: The intervention seems to have had no effect on quality of prescriptions or quality of life. This underlines the major challenge of fi nding new strategies for improving prescription quality to improve patient outcome measures such as quality of life and reduce the known risks of polypharmacy for the elderly.

Background: Body height is a classic polygenic trait. About 80%-90% of height is inherited and 10%-20% owed to environmental factors, of which the most important ones are nutrition and diseases in preadolescents and adolescents.

Objective: The aim of this study was to explore potential relations between the LCT (lactase) C > T-13910 polymorphism, milk consumption, and body height in a sample of Swedish preadolescents and adolescents.

Design: In a cross-sectional study, using a random sample of preadolescents and adolescents (n = 597), dietary intakes were determined. Anthropometric measurements including sexual maturity (Tanner stage) and birth weight were assessed. Parental body height and socio-economic status (SES) were obtained by questionnaires. Genotyping for the LCT C > T-13910 polymorphism that renders individuals lactase persistent (LP) or lactase non-persistent (LNP) was performed by DNA sequencing. Stepwise backward multivariate linear regression was used.

Results: Milk consumption was significantly and positively associated with body height (beta =0.45; 95% CI: 0.040, 0.87, p =0.032). Adjustments were performed for sex, parental height, birth weight, body mass index (BMI), SES, and Tanner stage. This model explains 90% of the observed variance of body height (adjusted R-2 =0.89). The presence of the -13910 T allele was positively associated with body height (beta = 2.05; 95% CI: 0.18, 3.92, p =0.032).

Conclusions: Milk consumption is positively associated with body height in preadolescents and adolescents. We show for the first time that a nutrigenetic variant might be able to explain in part phenotypic variation of body height in preadolescents and adolescents. Due to the small sample size further studies are needed.

Background: Modern drugs have made large contributions to better health and quality of life. Increasing proportions of negative side effects due to extensive pharmacological treatment are however observed especially among elderly patients who have multiple health problems. The aim of our study was to see if there is an association between medication quality and quality of life.

Methods: 150 patients discharged from hospital. Inclusion criteria were: living in ordinary homes, ≥ 75 years and ≥ 5 drugs. Home visits were performed to all, including prescription reviews and calculation of medication appropriateness index. The patients were divided into three groups depending on index score and followed for 12 months. The validated and recognized EQ-5D and EQ VAS instruments were used to assess quality of life.

Results: A lower medication quality was associated with a lower quality of life. EQ-5D index was statistically significantly different (declining for each group) among the groups (p = 0.001 at study start, p = 0.001 at 6 months and p = 0.013 at 12 months) as was EQ VAS (p = 0.026 at study start, p = 0.003 at 6 months and p = 0.007 at 12 months).

Conclusions: This study has shown the validity of the basic principle in prescribing: the more appropriate medication the better quality of life. Since drug quality is related to the patients’ quality of life, there is immense reason to continuously evaluate every prescription and treatment. The evaluation and if possible deprescribing should be done as a process where both the patient and physician are involved.

AIM:To investigate the effects of a nurse-led multidisciplinary programme (NMP) of pulmonary rehabilitation in primary health care with regard to functional capacity, quality of life (QoL), and exacerbations among patients with chronic obstructive pulmonary disease (COPD).

METHOD:A 1-year longitudinal study with a quasi-experimental design was undertaken in patients with COPD, 49 in the intervention group and 54 in the control group. Functional capacity was assessed using the 6-minute walking test, and quality of life (QoL) was assessed using the Clinical COPD Questionnaire. Exacerbations were calculated by examination of patient records.

RESULTS:No significant differences were found between the groups in functional capacity and QoL after 1 year. The exacerbations decreased in the intervention group (n = -0.2) and increased in the control group (n = 0.3) during the year after NMP. The mean difference of change in exacerbation frequency between the groups was statistically significant after one year (p=0.009).

CONCLUSIONS:The NMP in primary care produced a significant reduction in exacerbation frequency, but functional capacity and QoL were unchanged. More and larger studies are needed to evaluate potential benefits in functional capacity and QoL.

The aim of the study was to describe how women with hirsutism experience their relationship with health care. Data were collected by tape-recorded individual interviews, which were analyzed by means of qualitative content analysis. The results showed that the relationship with health care, from the perspective of patients with hirsutism, is suboptimal.