Single-dose and steady-state pharmacokinetics of diltiazem administered in two different tablet formulations.

Single-dose and steady state pharmacokinetics of diltiazem administered in two different oral formulations were assessed with particular reference to rate and extent of absorption. Following single dose administration a significant difference in tmax was observed (2.9 +/- 1.9 and 6.8 +/- 2.6 hr respectively) whereas differences in AUC, t1/2 and Cmax were not significant. The AUC (mean +/- S.D.) values following single dose administration of Cardil and Cardizem were 678.4 +/- 321.5 and 948.6 +/- 580.6 ng.ml-1.hr respectively. The mean and the 95% confidence limits for the observed ratio AUCCardil/AUCCardizem are 0.89 and 0.44-1.34 respectively. At steady-state a significant difference between Cmax/Cmin and tmax was seen Cmax/Cmin being 4.9 and 3.2 respectively and Tmax being 2.7 +/- 2.0 and 6.0 +/- 2.8 hr respectively, whereas Cmax and AUC did not differ significantly. The AUC (mean +/- S.D.) values in steady state of Cardil and Cardizem were 880.1 +/- 399.8 and 1056.8 +/- 509.8 ng.ml-1.hr respectively. The mean and the 95% confidence limits for the observed ratio AUCCardil/AUCCardizem are 0.96 and 0.66-1.26 respectively. Although the observed ratios AUCCardil/AUCCardizem in both the single-dose and the steady-state study do not differ significantly from 1.0, the confidence limits exceed the acceptable values given by Poulsen & Juul (personal communication 1990) (a 20% decrease or increase of the ratio to 0.8 or 1.2).     

A longitudinal study of semen quality in pesticide spraying danish farmers

It was hypothesized that occupational exposure to pesticides during a spraying season causes changes in semen quality that might be detected in a longitudinal study. We analyzed the within-person changes in semen quality and reproductive hormones across a spraying season in groups of farmers using and not using pesticides. A total of 248 men collected two semen samples (participation rate: 32%). The median sperm concentration declined significantly from the first to the second sample in both groups, but there was no statistical difference in the decline between the two groups, unadjusted or adjusted. Only minor changes were found in sperm morphology, vitality, motility, sperm chromatin denaturation (SCSA), and reproductive hormones, and the differences in changes between the two groups were nonsignificant, or, in the opposite direction to the expected. There was no relation between the changes in sperm parameters in relation to pesticide exposure variables. In conclusion, use of pesticides by Danish farmers is not a likely cause of short-term effects on semen quality and reproductive hormones.     

Identifying environmental risk to male reproductive function by occupational sperm studies: logistics and design options.

Malfunction of the male reproductive system might be a sensitive marker of environmental hazards, the effects of which may extend beyond reproductive function. The testis is more vulnerable to heat and ionising radiation than any other organ of the body and several xenobiotics are known to disrupt spermatogenesis after low level exposure. Studies of environmental impact on human health are often most informative and accurate when carried out in the workplace where exposures can be high and easy to document. Semen analysis provides readily obtainable information on testicular function. The main advantages in comparison with functional measures such as fertility rates and time taken to conceive are the possibilities to examine men independently of marriage and pregnancy, to find changes of fecundity with different exposures within the same person and to detect adverse effects when no alteration of fertility is yet taking place. In the implementation of an occupational sperm study considerable attention must be paid to logistic issues. A mobile laboratory unit for initial semen preparation and processing may in some situations increase worker compliance and the quality of sperm cell motility. The cross sectional design which has been used in almost all male reproductive studies so far has several severe limitations including selection bias because of differential participation, difficulties in defining a suitable reference group, and lack of information about the time dimension of the cause-effect relation. The longitudinal design deals adequately with most of these constraints. Semen samples are collected before, during, and possibly after exposure to the risk factor of interest and causal inferences are based upon change of semen variables within a man over time rather than upon differences between men. The logistics of the longitudinal study may benefit from pre-employment health examinations to enrol newly hired workers and require fewer participants to obtain comparable statistical power. In conclusion, andrological methods and epidemiological designs are available for the implementation of valid studies concerned with environmental impact on human testicular function. Occupational sperm studies should probably not be the first choice when the objective is initial screening of environmental impact on fertility but should be implemented when their is a need to corroborate or refuse earlier evidence that specific exposures have impact on testicular function.     

Using infertile patients in epidemiologic studies on subfecundity and embryonal loss

Subfecundity is a frequent and serious problem that may sometimes be preventable, but we need to know more about its determinants. Different epidemiologic designs are available. The best of these use prospectively collected data from the population, but they are time consuming, expensive and often hampered by low-participation rates. Most patients undergoing infertility treatment are closely monitored for clinical reasons, making it feasible to use secondary data to study the period from conception to implantation and pregnancy. In spite that infertility patients are highly selected, there are specific exposure-effect relations that can be studied in cohorts of infertility patients. These patients offer a potentially useful setting for studying exposures that operate late in fertilization, whereas the designs may be inadequate to identify exposures that cause reduced sperm counts, anovulation and total occlusion. The clinical sampling and the treatment set limitations for what can be studied. In certain situations, infertile patients can, however, provide useful epidemiologic evidence for learning about the causes of subfecundity.     

Engagement with arts and culture activities in the Danish general population: Longitudinal associations with new onset or persistent depression and mental wellbeing

Objectives

International literature suggests that arts and culture activities may benefit mental health, however, such survey studies conducted in the Danish population are scarce. Further, studies have investigated the associated risk for incident depression, but not for persistent depression. The objective of the current prospective study was to assess associations of engagement in arts and culture activities with incident/persistent depression and also mental wellbeing among Danish adults in the general population.

Design

Observational prospective study.

Methods

Data stem from a Danish nationally representative panel study of 5000 adults (aged 15+ years) conducted in 2019 and 2020, which was linked to Danish register data. An exposure variable was constructed for frequency of attending concerts, theatres, museums, and cinemas. Validated scales were used to assess the presence of depression (PHQ-8) and levels of mental wellbeing (SWEMWBS). Binary logistic regression analyses were conducted to assess the risk of incident depression (among participants free of depression at baseline), as well as the risk of persistent depression (among participants with depression at baseline), while multinomial logistic regression was used to assess odds for moderate and high mental wellbeing (low as base outcome) while adjusting for baseline values.

Result

In terms of incident depression, quarterly engagement in arts and culture activities (compared to never) was associated with an OR of .43 (95%CI .23–.80), while 8 times or more was associated with an OR of .53 (.29–.97). In terms of persistent depression, quarterly engagement was associated with an OR of .30 (.10–.90), while 8 times per year or more was associated with an OR of .26 (.07–.92). Similar to the patterns for incident/persistent depression, associations with moderate mental wellbeing showed higher odds for quarterly engagement and 8 times per year or more. Quarterly engagement was also associated with higher odds for high mental wellbeing but did not reach statistical significance.

Conclusions

The results support the involvement of the cultural and creative sectors in health strategies. Mental health promotion initiatives as well as arts and culture sectors may encourage the general public to engage in arts and culture activities with frequencies of at least once per quarter.     

Semen quality and sex hormones among organic and traditional Danish farmers. ASCLEPIOS Study Group

OBJECTIVES: To confirm or refute the hypothesis that organic farmers have higher sperm concentrations than traditional farmers. METHODS: Traditional and organic farmers were selected randomly from central registers, and 171 traditional farmers and 85 organic farmers delivered one semen sample before the start of the spraying season. The participation rate was 28.8% among traditional farmers and 42.9% among organic farmers. RESULTS: The median sperm concentration for traditional and organic farmers was 58 million/ml and 64 million/ml, respectively. After adjustment for several confounders, sperm concentration, total count, proportion of non-vital spermatozoa, sperm chromatin structure, and motility variables did not differ significantly between the two groups. The traditional farmers had a significantly lower proportion of normal spermatozoa, but this result was not confirmed in a second sample. Organic farmers had slightly higher inhibin B concentration and testosterone/sex hormone binding globulin ratio. CONCLUSION: Despite slight differences in concentrations of reproductive hormones, no significant differences in conventional measures of semen quality were found between organic and traditional farmers.

 

     

Implementation of percutaneous dilation tracheotomy – value of preincisional ultrasonic examination?

BACKGROUND: In this observational study we have evaluated the implementation of percutaneous dilation tracheotomy (PDT), using the forceps dilation technique (Portex) in a multidisciplinary ICU. METHODS: We included a preincisional ultrasonic evaluation of the neck in order to visualise the isthmus glandula thyroidea and major vessels. The observational period comprised one year. PDT was performed in 28 patients. RESULTS: Implementation of PDT was uneventful. Duration of insertion was 10 min (4-40 min). Total time of tracheostomy was 8 days (1-65 days). In nine cases, the proximal end of the isthmus was overlying the space between the 1st and 2nd tracheal ring, which was considered the optimal insertion site. This resulted in seven cases of insertion between the cricoidea and the 1st tracheal ring and in two cases in a more distal insertion. Nineteen tracheotomies were performed in the interstice between the 1st and 2nd tracheal ring. In nine patients, major vessels were overlying the trachea. In none of the patients did this information result in an altered insertion site. Two cases of minor bleeding were observed; both stopped upon compression. In two patients the primary tube size (8.0) was too big and a smaller tube had to be inserted. In one patient the tube was maladapted to the stoma and had to be interchanged with an ordinary tracheostomial tube on the 5th day of tracheostomy. CONCLUSION: Based on the experience gathered in this study and information from the literature, we have abandoned the routine use of ultrasonic examination of the neck prior to PDT. In order to achieve and maintain routine, we suggest that the procedure is performed by a restricted number of doctors.     

Environmental fertility research at the turn of the century

Research into environmental causes of impaired human fertility is still immature. Knowledge on the strengths and limitations of several research options, the main sources of bias, the occurrence of infertility and subfecundity in several countries, the patterns of contraceptive behavior, and the distribution of sperm counts at the population level has advanced, but the much-debated questions about temporal and regional trends in fertility and semen quality remain unsettled. Refined biological markers of male fecundity and markers feasible for large-scale studies of female fecundity are needed. The effects of several life-style factors have been characterized successfully, but the detrimental effects of environmental exposures have not. Most studies are either inconclusive or fail to demonstrate any important risks. If comprehensive knowledge on biological mechanisms is a criterion of maturity, epidemiologic and toxicologic fertility research is young. The new millennium will be challenged to determine the role played by the environment in developed countries, wrong exposure time windows, too crude or inappropriate measures of fertility, and overlooked critical exposures.