Human leukocyte antigen B (HLA‐B) is a gene that encodes a cell surface protein involved in presenting antigens to the immune system. The variant allele HLA‐B*15:02 is associated with an increased ...risk of Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in response to carbamazepine treatment. We summarize evidence from the published literature supporting this association and provide recommendations for the use of carbamazepine based on HLA‐B genotype (also available on PharmGKB: http://www.pharmgkb.org). The purpose of this article is to provide information to allow the interpretation of clinical HLA‐B*15:02 genotype tests so that the results can be used to guide the use of carbamazepine. The guideline provides recommendations for the use of carbamazepine when HLA‐B*15:02 genotype results are available. Detailed guidelines regarding the selection of alternative therapies, the use of phenotypic tests, when to conduct genotype testing, and cost‐effectiveness analyses are beyond the scope of this document. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines are published and updated periodically on the PharmGKB website at (http://www.pharmgkb.org).
Clinical Pharmacology & Therapeutics (2013); 94 3, 324–328. doi:10.1038/clpt.2013.103
Both the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dutch Pharmacogenetics Working Group provide therapeutic recommendations for well‐known gene‐drug pairs. Published ...recommendations show a high rate of concordance. However, as a result of different guideline development methods used by these two consortia, differences between the published guidelines exist. The aim of this paper is to compare both initiatives and explore these differences, with the objective to achieve harmonization.
The Sustainable Development Goal (SDG) target 3.4 is to reduce premature mortality from non-communicable diseases (NCDs) by a third by 2030 relative to 2015 levels, and to promote mental health and ...wellbeing. We used data on cause-specific mortality to characterise the risk and trends in NCD mortality in each country and evaluate combinations of reductions in NCD causes of death that can achieve SDG target 3.4. Among NCDs, ischaemic heart disease is responsible for the highest risk of premature death in more than half of all countries for women, and more than three-quarters for men. However, stroke, other cardiovascular diseases, and some cancers are associated with a similar risk, and in many countries, a higher risk of premature death than ischaemic heart disease. Although premature mortality from NCDs is declining in most countries, for most the pace of change is too slow to achieve SDG target 3.4. To investigate the options available to each country for achieving SDG target 3.4, we considered different scenarios, each representing a combination of fast (annual rate achieved by the tenth best performing percentile of all countries) and average (median of all countries) declines in risk of premature death from NCDs. Pathways analysis shows that every country has options for achieving SDG target 3.4. No country could achieve the target by addressing a single disease. In at least half the countries, achieving the target requires improvements in the rate of decline in at least five causes for women and in at least seven causes for men to the same rate achieved by the tenth best performing percentile of all countries. Tobacco and alcohol control and effective health-system interventions—including hypertension and diabetes treatment; primary and secondary cardiovascular disease prevention in high-risk individuals; low-dose inhaled corticosteroids and bronchodilators for asthma and chronic obstructive pulmonary disease; treatment of acute cardiovascular diseases, diabetes complications, and exacerbations of asthma and chronic obstructive pulmonary disease; and effective cancer screening and treatment—will reduce NCD causes of death necessary to achieve SDG target 3.4 in most countries.
The goal of this study was to objectively assess the effect of a platelet-rich plasma (PRP) derivate in English bulldogs with stifle degenerative joint disease secondary to cranial cruciate ligament ...rupture (CCLR). We used a force platform and affixed electrogoniometers to measure peak vertical force (PVF), vertical impulse (VI), stance time (ST), and angular range of motion (AROM), from 12 lame client-owned English bulldogs with post-CCLR stifle joint abnormalities. The 12 affected subjects were treated with 4 intra-articular injections of PRP, at 30-day intervals. Ten untreated, sound English bulldogs were used as a reference group. Clinical outcomes were evaluated using a linear mixed effects model. Mean values of PVF, VI, ST, and AROM were improved within the first 3 months post-treatment in the CCLR group, with mean measured changes increasing to maximum 4.56% body weight gain, 1.5% body weight/second, 0.07 seconds, and 6.18 degrees, respectively. The effects declined progressively after the treatment interval, ending at nearly initial levels after 6 months. This study demonstrates that dogs with CCLR treated with intra-articular PRP had improved PVF, VI, ST, and AROM over time; the duration of effect was waning by the end of the post-treatment period.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Simplified blood pressure (BP) screening approaches have been proposed. However, evidence is limited to a few countries and has not documented the cardiovascular risk amongst missed hypertension ...cases, limiting the uptake of these simplified approaches. We quantified the proportion of missed, over-diagnosed, and consistently identified hypertension cases and the 10-year cardiovascular risk in these groups.
We used 60 WHO STEPS surveys (cross-sectional and nationally representative; n = 145,174) conducted in 60 countries in 6 world regions between 2004 and 2019. Nine simplified approaches were compared against the standard (average of the last 2 of 3 BP measurements). The 10-year cardiovascular risk was computed with the 2019 World Health Organization Cardiovascular Risk Charts. We used t tests to compare the cardiovascular risk between the missed and over-diagnosed cases and the consistent hypertension cases. We used Poisson multilevel regressions to identify risk factors for missed cases (adjusted for age, sex, body mass index, and 10-year cardiovascular risk). Across all countries, compared to the standard approach, the simplified approach that missed the fewest cases was using the second BP reading if the first BP reading was 130-145/80-95 mm Hg (5.62%); using only the second BP reading missed 5.82%. The simplified approach with the smallest over-diagnosis proportion was using the second BP reading if the first BP measurement was ≥140/90 mm Hg (3.03%). In many countries, cardiovascular risk was not significantly different between the missed and consistent hypertension groups, yet the mean was slightly lower amongst missed cases. Cardiovascular risk was positively associated with missed hypertension depending on the simplified approach. The main limitation of the work is the cross-sectional design.
Simplified BP screening approaches seem to have low misdiagnosis rates, and cardiovascular risk could be lower amongst missed cases than amongst consistent hypertension cases. Simplified BP screening approaches could be included in large screening programmes and busy clinics.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•HIU is a potential technology for adoption in the dairy industry.•Ultrasound significantly modifies the components in milk.•Ultrasound improves gelation and syneresis during cheese ...production.•The texture of dairy products can be manipulated by ultrasound.•Ultrasound reduces fermentation time or dairy products.•Improvements depend on time, frequency and intensity of sonication.
Alternative methods for improving traditional food processing have increased in the last decades. Additionally, the development of novel dairy products is gaining importance due to an increased consumer demand for palatable, healthy, and minimally processed products. Ultrasonic processing or sonication is a promising alternative technology in the food industry as it has potential to improve the technological and functional properties of milk and dairy products. This review presents a detailed summary of the latest research on the impact of high-intensity ultrasound techniques in dairy processing. It explores the ways in which ultrasound has been employed to enhance milk properties and processes of interest to the dairy industry, such as homogenization, emulsification, yogurt and fermented beverages production, and food safety. Special emphasis has been given to ultrasonic effects on milk components; fermentation and spoilage by microorganisms; and the technological, functional, and sensory properties of dairy foods. Several current and potential applications of ultrasound as a processing technique in milk applications are also discussed in this review.
The overall increase of chronic degenerative diseases associated with ageing makes wound care a tremendous socioeconomic burden. Thus, there is a growing need to develop novel wound healing therapies ...to improve cutaneous wound healing. The use of regenerative therapies is becoming increasingly popular due to the low-invasive procedures needed to apply them. Platelet-rich plasma (PRP) is gaining interest due to its potential to stimulate and accelerate the wound healing process. The cytokines and growth factors forming PRP play a crucial role in the healing process. This article reviews the emerging field of skin wound regenerative therapies with particular emphasis on PRP and the role of growth factors in the wound healing process.
Thiopurine methyltransferase (TPMT) activity exhibits monogenic co‐dominant inheritance, with ethnic differences in the frequency of occurrence of variant alleles. With conventional thiopurine doses, ...homozygous TPMT‐deficient patients (~1 in 178 to 1 in 3,736 individuals with two nonfunctional TPMT alleles) experience severe myelosuppression, 30–60% of individuals who are heterozygotes (~3–14% of the population) show moderate toxicity, and homozygous wild‐type individuals (~86–97% of the population) show lower active thioguanine nucleolides and less myelosuppression. We provide dosing recommendations (updates at http://www.pharmgkb.org) for azathioprine, mercaptopurine (MP), and thioguanine based on TPMT genotype.
Clinical Pharmacology & Therapeutics (2011) 89 3, 387–391. doi:10.1038/clpt.2010.320
The Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Thiopurine Methyltransferase Genotype and Thiopurine Dosing was originally published in March 2011. We reviewed recent ...literature and concluded that although relevant new evidence has been generated, none of the evidence would change the primary dosing recommendations in the original guideline; therefore, the original publication remains clinically current. Up‐to‐date information on thiopurine methyltransferase (TPMT) gene alleles and nomenclature can be found at PharmGKB (http://www.pharmgkb.org).
Clinical Pharmacology & Therapeutics (2013); 93 4, 324–325. doi:10.1038/clpt.2013.4
Background
Screening for type 2 diabetes mellitus (T2DM) targets people aged 35+ years and those with overweight/obesity. With mounting evidence on young‐onset T2DM and T2DM patients with lean ...phenotypes, it is worth revising the screening criteria to include younger and leaner adults. We quantified the mean age and body mass index (BMI; kg/m2) at T2DM diagnosis in 56 countries.
Methods
Descriptive cross‐sectional analysis of WHO STEPS surveys. We analysed adults (25–69 years) with new T2DM diagnosis (not necessarily T2DM onset) as per fasting plasma glucose ≥126 mg/dL measured during the survey. For people with new T2DM diagnosis, we summarized the mean age and the proportion of each five‐year age group; also, we summarized the mean BMI and the proportion of mutually exclusive BMI categories.
Results
There were 8695 new T2DM patients. Overall, the mean age at T2DM diagnosis was 45.1 years in men and 45.0 years in women; and the mean BMI at T2DM diagnosis was 25.2 in men and 26.9 in women. Overall, in men, 10.3% were 25–29 years and 8.5% were 30–34 years old; in women, 8.6% and 12.5% were 25–29 years and 30–34 years old, respectively. 48.5% of men and 37.3% of women were in the normal BMI category.
Conclusions
A non‐negligible proportion of new T2DM patients were younger than 35 years. Many new T2DM patients were in the normal weight range. Guidelines for T2DM screening may consider revising the age and BMI criteria to incorporate young and lean adults.
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