Increased brain uptake of venlafaxine loaded solid lipid nanoparticles by overcoming the efflux function and expression of P-gp

Venlafaxine (VLX) could be pumped out of the brain by P-glycoprotein (P-gp). Moreover, the expression of P-gp distributed in blood–brain barrier could be significantly induced by VLX. Thus, P-gp could be considered as the nature barrier for delivering of VLX to the brain. The aim of this study was to investigate whether the efflux function and increased expression of P-gp could be reversed by utilizing solid lipid nanoparticles (SLN). VLX solid lipid nanoparticles (VLX ? SLN) were prepared and evaluated. Pharmacokinetics and brain distribution of VLX in different formulations were conducted after oral or intravenous administration. P-gp efflux function to VLX was evaluated by the brain uptake amount of VLX, while P-gp expression was investigated by Western blotting. Results indicated that the entrapment, mean size and zata potential of VLX ? SLN was 74.9 ± 3.0 %, 186.3 ± 69.26 nm and ?22.8 ± 7.78 mv, respectively. After vein injection of VLX formulations, the brain uptake amount of VLX from VLX ? SLN was significantly higher than that of VLX solution, VLX solution with empty SLN (VLX+ empty SLN) and VLX solution with Verapamil (VLX + Ver), respectively. Furthermore, the protein mass of P-gp in VLX ? SLN treated group was the lowest among all the investigated groups. These results indicated that SLN could overcome P-gp and achieve brain target by intravenous administration.     

Enhancement of solubility and dissolution of cilostazol by solid dispersion technique

Cilostazol is practically insoluble in water and thus results in poor bioavailability. Only a few approaches have been reported for improving the bioavailability of cilostazol. Solid dispersion technique via solvent evaporation method was applied to improve the solubility and dissolution of cilostazol. Various polymers, mixture of polymer and surfactant, and mixture of polymers were screened as a carrier for the solid dispersion. Solubility of cilostazol was improved significantly when Eudragit^® L100 was used as a carrier. However, addition of surfactant to Eudragit^® L100 decreased the solubility slightly. Whereas, the mixture of Eudragit^® L100 and Eudragit^® S100 as a carrier system further increased the solubility. Based on the highest solubility obtained among the carriers screened, 1:1 ratio of Eudragit^® L100 and Eudragit^® S100 was selected as a carrier, and drug to carrier ratio was optimized to 1:5. Differential scanning calorimetry and X-ray diffraction studies showed that the characteristic peak of cilostazol disappeared in the solid dispersion, indicating that cilostazol existed in amorphous form in this formulation. Spray drying method was superior to vacuum drying method in terms of dissolution rate. Meanwhile, it was observed that the disintegration rate and the concentration of polymer had some effect on the crystallization of cilostazol in dissolution medium. Tablet formulation containing spray dried solid dispersion showed significant improvement in dissolution as compared to the commercial tablet.     

Ethnic Background,Socioeconomic Status,and Problem Severity as Dropout Risk Factors in Psychotherapy with Youth

Background

Dropout from child and adolescent psychotherapy is a common phenomenon which can have negative consequences for the individual later in life. It is therefore important to gain insight on dropout risk factors.

Objective

Several potential risk factors [ethnic minority status, a lower socioeconomic status (SES), and higher problem severity] were analyzed in present study. Innovations are that these risk factors were examined for children and adolescents separately, and a distinction was made in termination status between referred patients, dropouts and completers.

Methods

For ethnic majority and minority outpatient children (age 5–11, n = 399) and adolescents (age 12–20, n = 352) problem severity, ethnic background, SES, and treatment termination status (completer, dropout, referral) were specified. Multinomial logistic regression models were used as main method of analysis.

Results

For children, a Moroccan/Turkish ethnicity and higher externalizing scores were risk factors for being referred. For adolescents, a Surinamese/Antillean ethnicity, being female, being older, and lower parental SES occupation levels were risk factors for dropout.

Conclusions

Different dropout risk profiles emerged for children versus adolescents, and for dropouts versus referrals. Also, it depended on the specific ethnic background whether ethnic minority status was a predictor for dropout, and the relationship between SES and termination status differed by whether parental SES occupation or parental SES education were used as SES indicator. Professionals should thus be aware of these potential risk factors for dropout or referral when treating children and adolescents.

     

Determinant factors of the difference between self-reported weight and measured weight among Japanese

Objectives

To assess the difference between self-reported and measured weight values in Japanese men and women and to determine the underlying determinants of the differences between self-reported and measured values.

Methods

The data were collected from 363 general Japanese individuals aged 16–88 years living in Kumamoto prefecture. Participants completed a self-administered questionnaire designed for this study with self-reported weight and height values. Measured weight and height were measured immediately after questionnaire completion. Paired t-tests identified differences between self-reported and measured values by sex. Multiple-stepwise regression analysis examined the independent variables’ effects on the differences between self-reported and measured weights.

Results

Significant differences were found between self-reported and measured values for both sexes (p < 0.001). There was a significant negative relationship between the difference in an individual’s self-reported and measured weight in each sex, with higher measured weight individuals more likely to underestimate their weight. Multiple-stepwise regression analysis models explained 12.1 % (p < 0.01), 11.3 % (p < 0.01), and 5.6 % (p < 0.01) of the variance in all participants, men, and women, respectively. Significant effects were found for age, weight measurement frequency, and measured weight in total participants, weight measurement frequency, and measured weight for men, and age for women.

Conclusions

In this study, the mean absolute value of the weight and height variances proved the unreliability of self-reported weight and height values. This study’s findings suggest self-reported weight inaccuracy especially for obese populations. This should be adjusted when using it in epidemiological studies and healthcare planning.

     

Comparison of two dietary assessment methods by food consumption: results of the German National Nutrition Survey II

Purpose

To further characterise the performance of the diet history method and the 24-h recalls method, both in an updated version, a comparison was conducted.

Methods

The National Nutrition Survey II, representative for Germany, assessed food consumption with both methods. The comparison was conducted in a sample of 9,968 participants aged 14–80. Besides calculating mean differences, statistical agreement measurements encompass Spearman and intraclass correlation coefficients, ranking participants in quartiles and the Bland–Altman method.

Results

Mean consumption of 12 out of 18 food groups was higher assessed with the diet history method. Three of these 12 food groups had a medium to large effect size (e.g. raw vegetables) and seven showed at least a small strength while there was basically no difference for coffee/tea or ice cream. Intraclass correlations were strong only for beverages (>0.50) and revealed the least correlation for vegetables (<0.20). Quartile classification of participants exhibited more than two-thirds being ranked in the same or adjacent quartile assessed by both methods. For every food group, Bland–Altman plots showed that the agreement of both methods weakened with increasing consumption.

Conclusions

The cognitive effort essential for the diet history method to remember consumption of the past 4 weeks may be a source of inaccurateness, especially for inhomogeneous food groups. Additionally, social desirability gains significance. There is no assessment method without errors and attention to specific food groups is a critical issue with every method. Altogether, the 24-h recalls method applied in the presented study, offers advantages approximating food consumption as compared to the diet history method.

     

What can Pakistan do to address maternal and child health over the next decade?

Pakistan faces huge challenges in meeting its international obligations and agreed Millennium Development Goal targets for reducing maternal and child mortality. While there have been reductions in maternal and under-5 child mortality, overall rates are barely above secular trends and neonatal mortality has not reduced much. Progress in addressing basic determinants, such as poverty, undernutrition, safe water, and sound sanitary conditions as well as female education, is unsatisfactory and, not surprisingly, population growth hampers economic growth and development across the country. The devolution of health to the provinces has created challenges as well as opportunities for action. This paper presents a range of actions needed for change within the health and social sectors, including primary care, social determinants, strategies to reach the unreached, and accountability.     

Analysis of misoprostol and chlorhexidine policy gains in Pakistan: the advocacy experience of Mercy Corps Pakistan

While Pakistan has made progress toward achieving Millennium Development Goal 5 for maternal health, it is unlikely to achieve the target; further, it is also not on track for Millennium Development Goal 4 regarding child health. Two low-cost, temperature stable and life-saving drugs, misoprostol and chlorhexidine, can respectively avert maternal and newborn deaths, and are particularly pertinent for poor and marginalized areas which bear the brunt of maternal and newborn deaths in Pakistan. In response, Mercy Corps led focused advocacy efforts to promote changes in policies, protocols, and regulatory environments for misoprostol (2012–2014) and for chlorhexidine (2014). These short-duration advocacy projects facilitated significant policy gains, such as inclusion of misoprostol and chlorhexidine into province-specific essential drug lists, development and endorsement of clinical protocols for the two drugs by provincial health departments, inclusion of misoprostol into pre-service training curriculum for several health cadres, and application for registration of chlorhexidine (at the concentration required for newborn care) by two pharmaceutical companies. These results were achieved by a consultative and evidence-based process which generated feedback from community members, program implementers, and policymakers, and ultimately put the government in the driver’s seat to facilitate change. Community Action Dialogue forums were linked with provincial-level Technical Working Groups and Provincial Steering Committees, who passed on endorsed recommendations to the Health Secretary. The key factors which facilitated change were the identification of champions within the provincial health departments, prioritization of relationship building and follow-up, focus on concrete advocacy aims rather than broad objectives, and the use of multi-stakeholder forums to secure an enabling environment for the policy changes to take root. While these advocacy initiatives resulted in significant policy changes in Pakistan’s devolved health system, to ensure these policy changes have an impact on health outcomes, Pakistan should focus on the scale-up of appropriate use of chlorhexidine and misoprostol. Further, future policy initiatives in Pakistan should make use of similar multi-stakeholder policy forums, while ensuring a third party to facilitate the process so that civil society and community voices are not lost in the policy development discussion.     

Coverage of private sector community midwife services in rural Punjab,Pakistan: development and demand

Background

In 2007, the Government of Pakistan introduced a new cadre of community midwives (CMWs) to address low skilled birth attendance rates in rural areas; this workforce is located in the private-sector. There are concerns about the effectiveness of the programme for increasing skilled birth attendance as previous experience from private-sector programmes has been sub-optimal. Indonesia first promoted private sector midwifery care, but the initiative failed to provide universal coverage and reduce maternal mortality rates.

Methods

A clustered, stratified survey was conducted in the districts of Jhelum and Layyah, Punjab. A total of 1,457 women who gave birth in the 2 years prior to the survey were interviewed. χ² analyses were performed to assess variation in coverage of maternal health services between the two districts. Logistic regression models were developed to explore whether differentials in coverage between the two districts could be explained by differential levels of development and demand for skilled birth attendance. Mean cost of childbirth care by type of provider was also calculated.

Results

Overall, 7.9% of women surveyed reported a CMW-attended birth. Women in Jhelum were six times more likely to report a CMW-attended birth than women in Layyah. The mean cost of a CMW-attended birth compared favourably with a dai-attended birth. The CMWs were, however, having difficulty garnering community trust. The majority of women, when asked why they had not sought care from their neighbourhood CMW, cited a lack of trust in CMWs’ competency and that they wanted a different provider.

Conclusions

The CMWs have yet to emerge as a significant maternity care provider in rural Punjab. Levels of overall community development determined uptake and hence coverage of CMW care. The CMWs were able to insert themselves into the maternal health marketplace in Jhelum because of an existing demand. A lower demand in Layyah meant there was less ‘space’ for the CMWs to enter the market. To ensure universal coverage, there is a need to revisit the strategy of introducing a new midwifery workforce in the private sector in contexts of low demand and marketing the benefits of skilled birth attendance.

     

Who is excluded and how? An analysis of community spaces for maternal and child health in Pakistan

Background

The maternal, newborn, and child health (MNCH) indicators of Pakistan depict the deplorable state of the poor and rural women and children. Many MNCH programmes stress the need to engage the poor in community spaces. However, caste and class based hierarchies and gendered social norms exclude the lower caste poor women from accessing healthcare. To find pathways for improving the lives of the excluded, this study considers the social system as a whole and describes the mechanisms of exclusion in the externally created formal community spaces and their interaction with the indigenous informal spaces.

Methods

The study used a qualitative case study design to identify the formal and informal community spaces in three purposively selected villages of Thatta, Rajanpur, and Ghizer districts. Community perspectives were gathered by conducting 37 focus group discussions, based on participatory rural appraisal tools, with separate groups of women and men. Relevant documents of six MNCH programmes were reviewed and 25 key informant interviews were conducted with programme staff.

Results

We found that lower caste poor tenants and nomadic peasants were excluded from formal and informal spaces. The formal community spaces formed by MNCH programmes across Pakistan included fixed, small transitory, large transitory, and emerging institutional spaces. Programme guidelines mandated selection of community notables in groups/committees and used criteria that prevented registration of nomadic groups as eligible clients. The selection criteria and adverse attitude of healthcare workers, along with inadequacy of programmatic resources to sustain outreach activities also contributed to exclusion of the lower caste poor women from formal spaces. The informal community spaces were mostly gender segregated. Infrequently, MNCH information trickled down from the better-off to the lower caste poor women through transitory interactions in the informal domestic sphere.

Conclusion

A revision of the purpose and implementation mechanisms for MNCH programmes is mandated to transform formal health spaces into sites of equitable healthcare.

     

Impact of socio-economic status on hospital length of stay following injury: a multicenter cohort study

Background

Injury is second only to cardiovascular disease in terms of acute care costs in North America. One key to improving injury care efficiency is to generate knowledge on the determinants of resource use. Socio-economic status (SES) is a documented risk factor for injury severity and mortality but its impact on length of stay (LOS) for injury admissions is unknown. This study aimed to examine the relationship between SES and LOS following injury.This multicenter retrospective cohort study was based on adults discharged alive from any trauma center (2007–2012; 57 hospitals; 65,486 patients) in a Canadian integrated provincial trauma system. SES was determined using ecological indices of material and social deprivation. Mean differences in LOS adjusted for age, gender, comorbidities, and injury severity were generated using multivariate linear regression.

Results

Mean LOS was 13.5 days. Patients in the highest quintile of material/social deprivation had a mean LOS 0.5 days (95 % CI 0.1-0.9)/1.4 days (1.1-1.8) longer than those in the lowest quintile. Patients in the highest quintiles of both social and material deprivation had a mean LOS 2.6 days (1.8-3.5) longer than those in the lowest quintiles.

Conclusions

Results suggest that patients admitted for traumatic injury who suffer from high social and/or material deprivation have longer acute care LOS in a universal-access health care system. The reasons behind observed differences need to be further explored but may indicate that discharge planning should take patient SES into consideration.