Pharmacokinetics and pharmacodynamics of pravastatin in children with familial hypercholesterolemia

BACKGROUND: Pravastatin is a widely used statin in adults, but its pharmacokinetics in children is not known. Our aim was to determine the single-dose pharmacokinetics and the lipid-lowering effect and safety of short-term administration of pravastatin in children. METHODS: Twenty children (age range, 4.9-15.6 years) with heterozygous familial hypercholesterolemia ingested a single dose of 10 mg pravastatin. Plasma concentrations of pravastatin were measured for up to 10 hours. The patients then took 10 mg pravastatin orally once daily for 8 weeks. The concentration of serum lipids and safety laboratory parameters were measured before and after 8 weeks of treatment. RESULTS: The mean peak plasma concentration (C(max)) of pravastatin was 15.7 ng/mL (range, 1.6-55.0 ng/mL), and the mean time to reach C(max) was 1.4 hours (range, 0.5-4 hours). The mean elimination half-life of pravastatin was 1.6 hours (range, 0.85-4.2 hours). The area under the plasma concentration-time curve of pravastatin ranged from 5.7 to 58.9 ng. h/mL (mean value, 26.6 ng. h/mL). By 8 weeks of treatment, the serum concentration of total cholesterol had decreased 18% (P <.0001); low-density lipoprotein cholesterol, 21% (P <.0001); and triglycerides, 18% (not significant, P =.18). The concentration of high-density lipoprotein cholesterol had increased 8% (not significant, P =.13). Few transient adverse events occurred. No increases in serum alanine aminotransferase, creatine kinase, or creatinine level were observed. CONCLUSIONS: The pharmacokinetic and pharmacodynamic profile of pravastatin in children is similar to that reported for adults. In the short term, the daily dose of 10 mg pravastatin was well tolerated and moderately effective in decreasing the serum cholesterol concentration. However, further studies are needed on the long-term safety and efficacy of pravastatin in children.     

“It Got Likes,But I Don’t Think People Understood”: A Qualitative Study of Adolescent Experiences Discussing Type 1 Diabetes on Social Media

Background:The majority of adolescents with type 1 diabetes (T1D) integrate social media engagement into their daily lives. The aim of this study was to explore adolescents’ experiences and perspectives discussing their T1D on social media.Methods:Semi-structured interviews with adolescents with T1D were conducted in person and via telephone. Questions focused on the participant’s experiences utilizing social media to discuss T1D and factors that informed the nature of T1D-related social media engagement. Open coding and thematic content analysis were used to identify emergent themes that aligned with accepted domains of social media affordances.Results:Participants included 35 adolescents with T1D. Adolescents’ experiences related to discussing T1D on social media aligned with four affordances of social media: identity, cognitive, emotional, and social. The identity affordances of social media platforms allowed adolescents to curate online personas that selectively included their diagnosis of T1D, while managing the potential negative emotional and social implications linked to the stigma of T1D. Adolescents who decided to discuss T1D on social media leveraged cognitive affordances by providing and receiving diabetes management advice, emotional affordances by obtaining affirmation from peers, and social affordances by extending their network to include other individuals with T1D.Conclusions:Adolescents with T1D flexibly leverage the affordances offered by social media to access emotional support, information, and identity affirmation resources while navigating stigma-based social consequences. Our findings highlight the value of developing tools to support adolescents with T1D in comfortably discussing and receiving appropriate support about T1D on social media.     

Can South Asian Countries Cope with the Mental Health Crisis Associated with COVID-19?

International Journal of Mental Health and Addiction -     

Towards quantifying the aesthetic outcomes of breast cancer treatment: comparison of clinical photography and colorimetry

Rationale, aims and objectives Scarring is a significant cause of dissatisfaction for women who undergo breast surgery. Scar tissue may be clinically distinguished from normal skin by aberrant colour, rough surface texture, increased thickness (hypertrophy) and firmness. Colorimeters or spectrophotometers can be used to quantitatively assess scar colour, but they require direct patient interaction and can cost thousands of dollars. By comparison, digital photography is already in widespread use to document clinical outcomes and requires less patient interaction. Thus, assessment of scar coloration by digital photography is an attractive alternative. The goal of this study was to compare colour measurements obtained by digital photography and colorimetry. Methods Agreements between photographic and colorimetric measurements of colour were evaluated. Experimental conditions were controlled by performing measurements on artificial scars created by a make‐up artist. The colorimetric measurements of the artificial scars were compared with those reported in the literature for real scars in order to confirm the validity of this approach. We assessed the agreement between the colorimetric and photographic measurements of colour using a hypothesis test for equivalence, the intraclass correlation coefficient and the Bland–Altman method. Results Overall, good agreement was obtained for three parameters (L*a*b*) measured by colorimetry and photography from the results of three statistical analyses. Conclusion Colour measurements obtained by digital photography were equivalent to those obtained using colorimetry. Thus, digital photography is a reliable, cost‐effective measurement method of skin colour and should be further investigated for quantitative analysis of surgical outcomes.     

Sexological Competence of Different Rehabilitation Disciplines and Effects of a Discipline-specific Sexological Training

Dealing with sexual problems due to disease or disability is part of medical rehabilitation, but both patients and professionals experience barriers to discuss sexual issues. A brief discipline-specific sexological training for rehabilitation professionals was therefore developed and evaluated in two rehabilitation centers in The Netherlands. Among the 283 participants were physicians (42), physical therapists (38), occupational therapists (40), psychologists and social workers (26), nurses (101), and other disciplines (36). Measurements before training, after training, and at 3–4 months follow-up showed increase of self-rated sexological competence and of scores on the Knowledge, Comfort, Approach, and Attitudes towards Sexuality Scale (KCAASS) during the training that were maintained at follow-up. Disciplines differed in sexual competence before training and in increase of sexual competence after training. Implementation of the training in other rehabilitation centers is recommended.     

5alpha-reductase 2 polymorphisms as risk factors in prostate cancer

Prostate cancer is a significant cause of death in Western countries and is under the strong influence of androgens. The steroid 5alpha-reductase 2 catalyzes the metabolism of testosterone into the more potent androgen dihydrotestosterone in the prostate gland. The enzyme is a target in pharmacological treatment of benign prostatic hyperplasia using specific inhibitors such as finasteride. Makridakis et al. have characterized the V89L and A49T polymorphisms in recombinant expression systems. The L allelic variant has a lower Vmax/Km ratio than the V variant. In the A49T polymorphism, the T variant has an increased Vmax/Km ratio. We performed a population-based case-control study of the impact of the SRD5A2 V89L and A49T polymorphisms on the risk of prostate cancer. We also studied the relation between the genotypes and age at diagnosis, tumor, node, metastasis stage, differentiation grade, prostate specific antigen and heredity. The study included 175 prostate cancer patients and 159 healthy controls that were matched for age. There was an association with SRD5A2 V89L LL genotype and metastases at the time of diagnosis, OR 5.67 (95% CI 1.44-22.30) when adjusted for age, differentiation grade, T-stage and prostate specific antigen. Heterozygous prostate cancer cases that carried the SRD5A2 A49T AT genotype were significantly younger than cases that carried the AA genotype, (mean age 66 years vs 71, P = 0.038). The SRD5A2 V89L and A49T polymorphisms were, however, not associated with altered prostate cancer risk. Further studies of the V89L polymorphism may lead to better understanding of the etiology of prostate cancer metastases.     

The epidemiology of gastric cancer

The epidemiology of gastric cancer is remarkable for both its dramatic decline in incidence over the past century and its continuing presence as the second leading cause of cancer deaths worldwide despite this decline. Factors including increased consumption of fruits and vegetables, and decreased intake of salty foods have largely been credited for the decline. Epidemiologic studies continue to provide data on other gastric cancer risk factors, including associations with Helicobacter pylori infection, as well as dietary factors, tobacco, and alcohol intake. In response to the opposing trends of decreasing distal gastric cancer and increasing gastric cardia adenocarcinoma, studies are beginning to identify gastric cancer risk factors separately by tumor subsite. Future epidemiologic studies that include information on site of origin as well as molecular markers promise to yield more homogeneous classification of case groups, which will enhance identification of underlying disease processes.     

Noscapine alters microtubule dynamics in living cells and inhibits the progression of melanoma

Cellular microtubules, polymers of tubulin, alternate relentlessly between phases of growth and shortening. We now show that noscapine, a tubulin-binding agent, increases the time that cellular microtubules spend idle in a paused state. As a result, most mammalian cell types observed arrest in mitosis in the presence of noscapine. We demonstrate that noscapine-treated murine melanoma B16LS9 cells do not arrest in mitosis but rather become polyploid followed by cell death, whereas primary melanocytes reversibly arrest in mitosis and resume a normal cell cycle after noscapine removal. Furthermore, in a syngeneic murine model of established s.c. melanoma, noscapine treatment resulted in an 85% inhibition of tumor volume on day 17 when delivered by gavage compared with untreated animals (P 相似文献