Drinking water magnesium and cardiovascular mortality: A cohort study in Denmark, 2005-2016.

INTRODUCTION: Cardiovascular diseases are globally a major cause of death. Magnesium deficiency is associated with several diseases including cardiovascular diseases. OBJECTIVE: To examine if a low concentration of magnesium in drinking water is associated with increased cardiovascular mortality and mortality due to acute myocardial infarction and stroke. METHODS: A nationwide population-based cohort study using national health registries was used. A total of 4,274,132 individuals aged 30 years or more were included. Magnesium concentration in drinking water was estimated by linkage of residential addresses in the period 2005-2016 with the national drinking water quality monitoring database. The association between magnesium concentration in drinking water and cardiovascular mortality and mortality due to acute myocardial infarction and stroke was examined using a Poisson regression of number of deaths and logarithmic transformation of follow-up time as offset. The incidence rate ratio (IRR) was adjusted for differences in age, sex, calendar year, cohabitation, country of origin, and socioeconomic status. RESULTS: Median magnesium concentration in drinking water at inclusion was 12.4 mg/L (range: 1.37-54.2 mg/L). The adjusted IRR for cardiovascular mortality was 0.96 (95% CI: 0.94; 0.97) for the lowest magnesium quintile (<6.5 mg/L) as compared to the highest magnesium quintile (>21.9 mg/L). The adjusted IRR for mortality due to acute myocardial infarction and stroke was 1.22 (1.17; 1.27) and 0.96 (0.93; 0.99), respectively, for the lowest magnesium quintile as compared to the highest quintile A decreasing mortality due to acute myocardial infarction was seen with an increasing magnesium concentration in a dose-response manner. CONCLUSION: Low concentrations of magnesium in drinking water were associated with an increased mortality due to acute myocardial infarction. Low concentrations of magnesium in drinking water were associated with decreased cardiovascular mortality, and mortality due to stroke.

Muscle wound healing in rainbow trout (Oncorhynchus mykiss).

We followed the progression of healing of deep excisional biopsy punch wounds over the course of 365 days in rainbow trout (Oncorhynchus mykiss) by monitoring visual wound healing and gene expression in the healing muscle at regular intervals (1, 3, 7, 14, 38 and 100 days post-wounding). In addition, we performed muscle texture analysis one year after wound infliction. The selected genes have all previously been investigated in relation to vertebrate wound healing, but only few specifically in fish. The selected genes were interleukin (IL)-1ß, IL-6, transforming growth factor (TGF)-ß1 and -ß3, matrix metalloproteinase (MMP) -9 and -13, inducible nitric oxide synthase (iNOS), fibronectin (FN), tenascin-C (TN-C), prolyl 4-hydroxylase α1-chain (P4Hα1), lysyl oxidase (LOX), collagen type I α1-chain (ColIα1), CD41 and CD163. Wound healing progressed slowly in the presented study, which is at least partially due to the low temperature of about 8.5 °C during the first 100 days. The inflammation phase lasted more than 14 days, and the genes relating to production and remodeling of new extracellular matrix (ECM) exhibited a delayed but prolonged upregulation starting 1-2 weeks post-wounding and lasting until at least 100 days post-wounding. The gene expression patterns and histology reveal limited capacity for muscle regeneration in rainbow trout, and muscle texture analyses one year after wound infliction confirm that wounds heal with fibrosis. At 100 dpw epidermis had fully regenerated, and dermis partially regenerated. Scales had not regenerated even after one year. CD163 is a marker of "wound healing"-type M2c macrophages in mammals. M2 macrophage markers are as yet poorly described in fish. The pattern of CD163 expression in the present study is consistent with the expected timing of presence of M2c macrophages in the wound. CD163 may thus potentially prove a valuable marker of M2 macrophages - or a subset hereof - in fish. We subjected a group of fish to bathing in an immunomodulatory ß-glucan product during wound healing, but found this to have very limited effect on wound healing in contrast to a previously published study on common carp.

Short mandible - a possible risk factor for cleft palate with/without a cleft lip.

OBJECTIVES: To estimate the influence of a short mandible on the risk of developing a cleft palate with/without a cleft lip (CP). SETTING AND SAMPLE POPULATION: The retrospective sample consisted of 115 2-month-old Danish infants with CP, and 70 control infants with unilateral incomplete cleft lip (UICL). MATERIAL AND METHODS: Cephalometric X-rays were obtained. Mandibular length (Lm ) was measured and corrected for body length (Lb ) to remove influence of varying body length in the sample. Logistic regression was applied to the corrected mandibular length (Lmc ) to calculate the risk of having a cleft palate. RESULTS: The mean mandibular length in the group with CP was about 4 mm shorter than in the control group. Odds ratio (OR) was calculated to be 0.58 (95% confidence interval 0.48-0.68), implying that an individual's risk of cleft palate with/without a cleft lip increases about 50% per mm decrease in mandibular length. CONCLUSIONS: A special facial type including a short mandible is a possible risk factor for cleft palate, and it was found that the risk of cleft palate increases 58% per mm decreases in mandibular length.

Spatial modelling of the between-herd infection dynamics of bovine virus diarrhoea virus (BVDV) in dairy herds in Denmark.

According to the current literature BVDV-infected neighbours probably impose a high risk of infection of susceptible cattle herds. In the present study, the objective was to evaluate the risk of a dairy herd changing infection status (from not having persistently infected (PI) animals to having PI-animals) in relation to location and infection status of neighbouring cattle herds in Denmark. In total, 7921 dairy herds were included in the analysis of spatial and non-spatial risk factors. The spatial risk factors were derived based on the cattle herds in the neighbourhood (N=36,639 cattle herds). The neighbourhood was defined as the first order neighbouring cattle herds using a Delauney triangularization. In total, 13.3% of the dairy herds changed herd status to PI-herds during the study period that lasted from January 1, 1995, to June 30, 1996. The risk of becoming a PI-herd was negatively associated with the mean distance to the neighbouring herds (OR=0.7 for an increase of 1 km). Presence of PI-herds in the neighbourhood increased the risk of becoming a PI-herd (OR=1.37, 1.40, 1.70 for 1, 2, ≥3 PI-herds in the neighbourhood). Increasing herd size increased the risk of becoming a PI-herd (OR=3.9 for an increase of 10 cows). Regional differences were seen.

Overcoming trends in irregularly spaced locations by regional polish - exemplified by estimation of the range of influence between Salmonella Dublin-seropositive cattle herds.

The aim of the study was to develop a procedure to remove spatial trends in irregularly spaced data, with trends partly due to regional differences. Median polish is often used on regularly spaced (lattice) data where column and row medians are removed. For irregularly spaced data a low-resolution map of the spatial locations is often used where data locations are assigned to the nearest lattice node followed by median polish. In this study regional polish was developed. The inverse distance weighted median was calculated based on observations from locations in the neighbourhood of the actual observation. The regional polish residual is obtained as the difference between the observed value and the weighted median. The regional polish procedure was applied to Salmonella Dublin data showing strong regional trends. Estimation of the range of influence between cattle herds with positive S. Dublin herd status was considerably improved with a stable parameter estimate and reduced standard error.

Simulation of the K-function in the analysis of spatial clustering for non-randomly distributed locations--exemplified by bovine virus diarrhoea virus (BVDV) infection in Denmark.

The K-function is often used to detect spatial clustering in spatial point processes, e.g. clustering of infected herds. Clustering is identified by testing the observed K-function for complete spatial randomness modelled, e.g. by a homogeneous Poisson process. The approach provides information about spatial clustering as well as the scale of distances of clustering. However, there are several problems related to applying the K-function, e.g. estimation of the size of the study area and the assumption about modelling spatial random distribution of the events by, e.g. a homogeneous Poisson process. The objective of the present study was to develop a null hypothesis version of the K-function that overcomes the assumption about a specific underlying spatial distribution characterising complete spatial randomness. Furthermore, the objective was to develop an approach that does not include the estimation of the size of the study area. The paper presents a simulation procedure to derive the null hypothesis version of the K-function. The null hypothesis version of the K-function is simulated by random sampling of N(+) locations from the distribution of N observed locations (infected (N(+)) and non-infected (N-N(+))). The differences between the empirical and the estimated null-hypothesis version of the K-function are plotted together with the 95% simulation envelopes versus the distance, h. In this way we test if the spatial distribution of the infected herds differs from the spatial distribution of the herd locations in general. The approach also overcomes edge effects and problems with complex shapes of the study region. An application to bovine virus diarrhoea virus (BVDV) infection in Denmark is described.

[Quality assurance of drug therapy for patients with asthma. Health economic analysis]. / Kvalitetssikring af astmapatienters laegemiddelbehandling. Sundhedsøkonomisk analyse.

The cost-effectiveness of a community pharmacy based programme for therapeutic outcomes monitoring of asthma patients' drug therapy is evaluated. Five hundred asthma patients, aged 16-60 and treated in primary care, with moderate to severe asthma, 31 community pharmacies and 139 general practitioners participated in the study. The total programme costs, costs of drugs, health care resource costs and indirect costs were evaluated together with the effects of the programme on: asthma symptoms status, days of sickness, quality of life, satisfaction with health care, peak-flow (PEF), inhalation technique and knowledge. The evaluation of the programme shows it to be cost-effective with cost-effectiveness ratios between 0.18 and 0.56. The pay off time for the programme is 23 months (range 9-64 months in the sensitivity analysis). It is concluded that the community pharmacist can contribute to identify and solve drug-related problems in a cost-effective way with positive impact on asthma patients health, clinical and psycho-social outcomes, even though the program is time consuming and intensive.

Surface-bounded growth modeling applied to human mandibles.

From a set of longitudinal three-dimensional scans of the same anatomical structure, we have accurately modeled the temporal shape and size changes using a linear shape model. On a total of 31 computed tomography scans of the mandible from six patients, 14,851 semilandmarks are found automatically using shape features and a new algorithm called geometry-constrained diffusion. The semilandmarks are mapped into Procrustes space. Principal component analysis extracts a one-dimensional subspace, which is used to construct a linear growth model. The worst case mean modeling error in a cross validation study is 3.7 mm.

Long-wave UVA offers partial protection against UVB-induced immune suppression in human skin.

Ultraviolet-B (UVB, 280-320 nm) interferes with the generation of cell-mediated immunity to contact allergens applied epicutaneously on the irradiated site. To investigate whether pretreatment with UVA-1 (340-400 nm) protects against the UVB-induced immune suppression we sensitized human volunteers with diphenylcyclopropenone (DPCP) on normal buttock skin (n= 12), on UVB-irradiated buttock skin (n=21), on buttock skin pretreated with UVA-1 (n= 12), and on buttock skin pretreated with UVA-1 and thereafter irradiated with UVB (n=22). Sensitization on UVB-irradiated skin reduced the immunization rate to DPCP compared with sensitization on non-irradiated skin (p<0.01) and skin pretreated with UVA-1 (p<0.01). In contrast, the immunization rate in the group of volunteers sensitized on skin pretreated with UVA-1 before UVB irradiation was significantly higher than the immunization rate in the group of volunteers sensitized on UVB-irradiated skin alone (p<0.05). These results indicate that pretreatment with UVA-1 under certain conditions offers partial protection against the UVB-induced reduction in the immunization rates to epicutaneous allergens.

A randomized, double-blind, placebo-controlled, dose-response study of the analgesic effect of lornoxicam after surgical removal of mandibular third molars.

The aim of the present study was to investigate the dose-effect relationship of single doses of 4 to 32 mg of lornoxicam (LNX), a new nonsteroidal antiinflammatory drug belonging to the oxicam group, compared with placebo and 10 mg ketorolac (KET) in the treatment of pain after oral surgery. Also, it was the aim of the study to evaluate the relationship between adverse events and different doses of LNX. After the surgical removal of a mandibular third molar, test medication was taken when the patients experienced at least moderate pain. After medication, pain relief, pain intensity, and any discomfort from the medication were noted in a questionnaire. Paracetamol was used as rescue medication. A total of 278 patients completed the study according to the protocol. The primary efficacy parameter was total pain relief after 6 hours, and all active treatments showed significantly better effect than placebo, with LNX 16 and 32 mg being significantly superior to LNX 4 mg. All other efficacy parameters showed the same dose-effect relationship. A total of 37 adverse events were reported evenly distributed in the 6 treatment groups; only 3 of these were considered severe, and all disappeared without treatment. In conclusion, the study showed a dose-effect relationship of LNX without a rise in adverse events. The effect of 10 mg KET seemed to be at the level of 8 to 16 mg LNX.