No sex-related differences but significant inhibition by oral contraceptives of CYP2C19 activity as measured by the probe drugs mephenytoin and omeprazole in healthy Swedish white subjects

BACKGROUND: Although it is known that the use of oral contraceptives inhibits oxidative drug metabolism, there is little information regarding their effect on CYP2C19 activity. Moreover, earlier reports suggest that there may be differences in CYP2C19 activity between men and women. OBJECTIVE: We sought to assess the effect of sex and intake of oral contraceptives on CYP2C19 activity as measured by the probe drugs mephenytoin and omeprazole. METHODS: To determine CYP2C19 activity in white Swedish subjects, 644 subjects previously phenotyped with mephenytoin and 175 subjects phenotyped with omeprazole were investigated. The 8-hour urinary mephenytoin S/R ratio after ingestion of 100 mg mephenytoin and the plasma concentration ratio of omeprazole/hydroxyomeprazole at 3 hours after ingestion of 20 mg omeprazole were used as measures of CYP2C19 activity. Differences in these ratios and in their frequency distributions were then examined among women with and without oral contraceptives and men. In addition, nearly all subjects in the omeprazole group had been genotyped with regard to the CYP2C19*2 (ml) allele. Subjects homozygous for the CYP2C19*2 allele were excluded from the study. RESULTS: The median mephenytoin S/R ratio was 2.5-fold higher in the subgroup of women taking oral contraceptives compared with either women not taking oral contraceptives (P < .001) or men (P < .001). Similarly, the mean omeprazole/hydroxyomeprazole ratio was twice as high in the oral contraceptive group compared with women not taking oral contraceptives (P < .001) or men (P < .001). However, no differences were evident between women not taking oral contraceptives and men in either the mephenytoin group (P = .48) or the omeprazole group (P = .77). The oral contraceptive-induced inhibitory effect on CYP2C19 activity was similar between the CYP2C19*1/*1 and *1/*2 genotypes, and they were independent of age. CONCLUSIONS: Intake of oral contraceptives significantly inhibits CYP2C19 activity, but there is no true sex-related difference in CYP2C19 activity in healthy, white, Swedish subjects.     

Importance of genetic factors in the regulation of diazepam metabolism: relationship to S-mephenytoin, but not debrisoquin, hydroxylation phenotype

Single oral 10 mg doses of diazepam and demethyldiazepam were given on different occasions to 16 healthy subjects. The subjects included four poor hydroxylators of debrisoquin and three poor hydroxylators of mephenytoin. There was a correlation between the total plasma clearance of diazepam and demethyldiazepam (rs = 0.83; p less than 0.01). There was no relationship between benzodiazepine disposition and debrisoquin hydroxylation. Poor hydroxylators of mephenytoin had less than half the plasma clearance of both diazepam (p = 0.0008) and demethyldiazepam (p = 0.0001) compared with extensive hydroxylators of mephenytoin. The plasma half-lives were longer in poor hydroxylators than they were in extensive hydroxylators of mephenytoin for both diazepam (88.3 +/- SD 17.2 and 40.8 +/- 14.0 hours; p = 0.0002) and demethyldiazepam (127.8 +/- 23.0 and 59.0 +/- 16.8 hours; p = 0.0001). There was no significant difference in volume of distribution of the benzodiazepines between the phenotypes. This study shows that the metabolism of both diazepam (mainly demethylation) and demethyldiazepam (mainly hydroxylation) is related to the mephenytoin, but not to the debrisoquin, hydroxylation phenotype.     

Quality of life and symptoms among older people living at home

AIM: This paper reports a study comparing the socio-demographic data, quality of life (QoL) and symptoms of older people living at home with and without help. BACKGROUND: Despite growing numbers of older people worldwide, little is know about the differences between older people receiving help to live at home and those not receiving this, especially as regards QoL and symptoms. Not only symptoms but also dependency on others per se may reduce older people's QoL. From a nursing perspective, knowledge about such issues is important because the impact of symptoms may be reducible, even when diseases cannot be cured. METHOD: A postal questionnaire was sent to an age-stratified random sample of 1866 people aged 75 years or over. Of the respondents (n = 1248) 448 received help and 793 did not. RESULTS: The group receiving help had a significantly higher age, more women, more people widowed and living alone, more children, a higher number of self-reported diseases and symptoms, greater inability to remain alone at home and lower QoL. Loneliness, depressed mood and abdominal pain were significantly related to low QoL in both groups. Living alone, not being able to remain alone at home without help, and fatigue were also predictive of low QoL among those receiving help, and number of diseases and sleep problems in those without. CONCLUSION: Receiving help with daily living seems to be significantly related to low QoL and goes along with a high number of symptoms that need to be considered in nursing care. Through regular visits, systematic assessment and intervention, especially focusing on older people's symptoms, nurses may contribute to improved QoL for this section of the population.     

Hand function and performance of daily activities in systemic lupus erythematosus

OBJECTIVE: To investigate hand problems in patients with systemic lupus erythematosus (SLE) and to explore consequences on the ability to perform daily activities. METHODS: One hundred nine patients with SLE completed a questionnaire assessing hand problems in terms of deficits in body structures, e.g., joints, and body functions including pain, grip force, and other physiologic functions of the hand, the Health Assessment Questionnaire (HAQ), and the Simple hand test. Patients who stated problems in hand function answered questions about performance of daily activities and to what extent different deficits in body structures and body functions interfered. RESULTS: Seventy-three percent of patients experienced hand problems and 42% reported interference with performance of daily activities. Problems from body structures of the hand were distributed relatively evenly over joints and tendons/muscles. Reduced grip force and activity-induced pain were the most commonly reported problems in body functions. The most affected activity area was productivity, namely household tasks, work at home, work/study, and child care; least affected was self-care. Reduced grip force followed by fumbling and pain were the most frequently reported body functions to create difficulties in performing daily activities. When comparing patients with and without difficulties in performing daily activities, there were significant differences in problems from tendons/muscles, joints in the thumb, reduced force, stiffness, fumbling, numbness/tingling, and the HAQ. CONCLUSION: A majority of the study group had hand problems and almost half of the group experienced difficulties in performing daily activities due to SLE. The most affected activity area was productivity, where reduced grip force, fumbling, and pain were the most interfering body functions.     

Comparison of the performance of rapid HIV tests using samples collected for surveillance in Mozambique

Mozambique had low HIV prevalence until the mid‐1990s, but recent data indicate increasing rates. There is little information on HIV‐2. Therefore, HIV seroprevalence was assessed among pregnant women and field‐ready HIV diagnostic strategies were evaluated. A total of 6,930 samples collected by three health centers from 2002 to 2005 were tested on site by nurses with two simple/rapid tests, Determine HIV‐1/2 (Abbott Laboratories; screening) and Uni‐Gold HIV (Trinity Biotech; confirmation), which is the national HIV testing strategy. The prevalence of HIV was 14.0% (2002), 17.8% (2003), 16.5% (2004), and 20.2% (2005). A subset of 888 samples collected 2003 was sent to the Central Microbiology Laboratory, Maputo for evaluation of tests and testing strategies. The assays included for comparison were Capillus HIV‐1/HIV‐2 (Trinity Biotech), DoubleCheckGold HIV‐1&2 (Orgenics) and Enzygnost Anti‐HIV‐1/2 Plus (Behringwerke, reference ELISA). Confirmation of reactive samples was done by Uni‐Gold HIV and ImmunoComb II HIV‐1&2 BiSpot (for HIV type differentiation). The Capillus HIV‐1/ HIV‐2 + ImmunoComb II HIV‐1&2 BiSpot combination was the gold standard. The sensitivity of the rapid/simple screening assays (Determine HIV‐1/2, DoubleCheckGold HIV‐1&2) was 100% (N = 160) and their (initial) specificities were 99.6% and 99.7%, respectively. Repeated testing and combinations of assays increased the specificity. Four suspected cases of recent seroconversion were found. Together with the increasing prevalence rates, this may indicate that Mozambique is a high‐incidence area, although further studies are needed to confirm this. Testing strategies for on‐site screening and confirmation based on the combination of Determine HIV‐1/2, Uni‐Gold HIV and DoubleCheckGold HIV‐1&2 are well suited for local field use. J. Med. Virol. 81:1991–1998, 2009. © 2009 Wiley‐Liss, Inc.     

Alcohol environment, gender and nonfatal injuries in young people. An ecological study of fourteen Swedish municipalities (2000–2005)

The Patient Protection and Affordable Care Act (PPACA) aims to provide affordable health insurance and expanded health care coverage for some 32 million Americans. The PPACA makes provisions for using technology, evidence-based treatments, and integrated, patient-centered care to modernize the delivery of health care services. These changes are designed to ensure effectiveness, efficiency, and cost-savings within the health care system. To gauge the addiction treatment field??s readiness for health reform, the authors developed a Health Reform Readiness Index (HRRI) survey for addiction treatment agencies. Addiction treatment administrators and providers from around the United States completed the survey located on the http://www.niatx.net website. Respondents self-assessed their agencies based on 13 conditions pertinent to health reform readiness, and received a confidential score and instant feedback. On a scale of ??Needs to Begin,?? ??Early Stages,?? ??On the Way,?? and ??Advanced,?? the mean scores for respondents (n?=?276) ranked in the Early Stages of health reform preparation for 11 of 13 conditions. Of greater concern was that organizations with budgets of?<?$5 million (n?=?193) were less likely than those with budgets?>?$5 million to have information technology (patient records, patient health technology, and administrative information technology), evidence-based treatments, quality management systems, a continuum of care, or a board of directors informed about PPACA. The findings of the HRRI indicate that the addiction field, and in particular smaller organizations, have much to do to prepare for a future environment that has greater expectations for information technology use, a credentialed workforce, accountability for patient care, and an integrated continuum of care.     

Occupational trajectories of working conditions in Sweden: Development trends in the workforce, 1997–2015

Objective:This study aimed to explore the development of working conditions within and between occupations in the Swedish labor market from 1997 to 2015 and whether any polarization in working conditions concurrently occurred between occupations.Methods:Cross-sectional data from ten waves of the Swedish Work Environment Surveys (1997–2015) were used and an aggregated occupational-level dataset was created using the Swedish Standard Classification of Occupations. To capture the patterns of change in working conditions over time (ie, growth), growth curve modeling was used to identify the starting points for 89 occupations (intercepts) as well as both the shape (functional form) and rate of growth (slope) over time.Results:The Swedish labor market was stable overall, with some small, mainly positive, changes in job demands and resources. Different occupations developed in divergent directions, but there was no evidence of polarization.Conclusions:The findings indicate that macro-level stability can hide highly heterogeneous patterns of change among different occupational groups. This type of analysis, taking context into account, could be valuable for decision makers intending to improve the work environment.     

Serum levels of 25‐hydroxyvitamin D in mothers of Swedish and of Somali origin who have children with and without autism

Aim: To analyse serum levels of 25‐hydroxyvitamin D in mothers of Somali origin and those of Swedish origin who have children with and without autism as there is a growing evidence that low vitamin D impacts adversely on brain development. Method: Four groups of mothers were invited to participate; 20 with Somali origin with at least one child with autism, 20 with Somali origin without a child with autism, 20 of Swedish origin with at least one child with autism and 20 with Swedish origin without a child with autism. Two blood samples were collected from each individual; during autumn and spring. Results: Between 12 and 17 mothers from the different groups accepted to participate, both groups of mothers of Somali origin had significantly lower values of 25‐hydroxyvitamin D compared with Swedish mothers. The difference of 25‐hydroxyvitamin D between mothers of Somali origin with and without a child with autism was not significant. Conclusion: Our findings of low vitamin D levels in Somali women entail considerable consequences in a public health perspective. The observed tendency, i.e. the lowest values in mothers of Somali origin with a child with autism was in the predicted direction, supporting the need for further research of vitamin D levels in larger samples of Somali mothers of children with and without autism.