Whole-process individualized pharmaceutical care for a case of melioidosis sepsis / 中国药房

OBJECTIVE To provide reference for the adjustment of antibiotic treatment regimens， identification of adverse reactions， and individualized pharmaceutical care for melioidosis sepsis （MS）. METHODS Clinical pharmacists participated in the intensive and eradicating therapeutic processes for an MS patient by using blood concentration and gene detection. Based on the literature， antibiotic treatment regimens of MS were adjusted by determining the blood concentrations of β-lactam and trimethoprim/ sulfamethoxazole （TMP/SMZ） and calculating PK/PD parameters. The causes of adverse drug reactions were analyzed and addressed by detecting drug-related gene polymorphisms through high-throughput sequencing. RESULTS Clinical pharmacists used blood concentration and genetic testing methods to propose adjustments to imipenem-cilastatin sodium dosage and analyze the causes of various adverse drug reactions. PK/PD targets were calculated by measuring the blood concentrations of β-lactam and TMP/SMZ. Clinical pharmacists explained to clinical doctors the compliance status of patients with melioidosis in sepsis and non- sepsis stages through reviewing guidelines and literature； the results of blood concentration and genetic test were used to analyze the correlation of neurotoxicity of MS patients with B14） IMP cmin， and it was found that nephrotoxicity was not related to the cmax of TMP/SMZ， but to the patient’s water intake. After whole-process antibiotic treatment， the patient’s condition improved and was discharged， and the adverse reactions were effectively treated. CONCLUSIONS Clinical pharmacists use blood concentration and genetic tests to assist clinicians in formulating MS treatment regimens， and provide whole-course pharmaceutical care for a MS patient. This method has improved the safety and effectiveness of clinical drug therapy.

Pitfalls in clinical genetics

With the increasing availability of genetic tests, more doctors are offering and ordering such tests for their patients. Ordering a genetic test appears to be a simple process of filling in paperwork, drawing 3 mL of blood in an ethylenediaminetetraacetic acid tube and receiving a test report. This is identical to sending off a full blood count. However, it is far more complex than that. There are many potential pitfalls, as shown by the increasing number of complaints and lawsuits filed against doctors and allied health staff. Furthermore, clinical genetics involves more than just ordering tests; in fact, focusing on genetic tests alone is a potential pitfall. In this review, we discuss the common pitfalls in clinical genetics and how doctors can avoid these pitfalls to ensure patient safety and to safeguard their practice.

Intolerância à lactose: diagnóstico clínico laboratorial e genético / Lactose intolerance: clinical and genetic diagnosis

Introdução: A intolerância à lactose é síndrome decorrente da má digestão do dissacarídeo lactose por deficiência da enzima lactase, gerando sintomas principalmente gastrintestinais. Ela envolve 4 causas principais: deficiência congênita de lactase; deficiência de lactase de desenvolvimento; intolerância primária à lactose; e deficiência secundária à lactase. Objetivo: Revisão da apresentação clínica da intolerância à lactose e os principais métodos disponíveis para seu diagnóstico clínico. Método: Revisão narrativa da base de dados PubMed, por meio das palavras-chave "lactose intolerance" e "genetic test" utilizando o descritor boleano and. Foram incluídos somente artigos em língua inglesa e publicados entre os anos de 2017 e 2022, totalizando 8 artigos. Resultado: O diagnóstico de intolerância à lactose relaciona-se com o seu tipo e utiliza-se dos principais métodos: teste oral de tolerância à lactose, teste genético, teste do hidrogênio expirado. Conclusão: Quanto aos métodos de diagnóstico, o teste do hidrogênio expirado é o de escolha, por não ser invasivo, possuir execução fácil e baixo custo. Entretanto, ele não dispensa associação com outras técnicas diagnósticas. O teste genético também é muito útil e sua vantagem é que não há necessidade da realização do teste oral de tolerância.

Introduction: Lactose intolerance is a syndrome resulting from maldigestion of the disaccharide lactose due to lactase enzyme deficiency causing symptoms mainly gastrointestinal. It involves 4 main causes: congenital lactase deficiency; developmental lactase deficiency; primary lactose intolerance; and secondary lactase deficiency. Objective: Review of the clinical presentation of lactose intolerance and the main methods available for its clinical diagnosis. Methods: Literature review in the PubMed database, using the keywords "lactose intolerance" and "genetic test" and using the Boolean data type and. Only articles in English and published between the years 2017 and 2022 were included, totalizing 8 articles. Results: The diagnosis of lactose intolerance is related to its type and uses the main diagnostic tests: oral lactose tolerance, genetic, expired hydrogen. Conclusion: Regarding diagnostic methods, the expired hydrogen test is the one of choice, as it is not invasive, is easy to perform and has low cost. However, it does not dispense association with other diagnostic techniques. Genetic testing is also very usefull and its advantage is that there is no need to use the oral lactose tolerance test.

Clinical features, gene diagnosis and pedigree analysis of Huntington disease in Sichuan Province / 中国神经精神疾病杂志

Objective To investigate the clinical characteristics of families with Huntington disease in Sichuan, and to make genetic diagnosis and pedigree analysis, and to provide genetic counseling for family members. Methods The detailed clinical data of Huntington disease patients and some family members who visited were collected from provincial people's Hospital of Sichuan between March 2016 and March 2018. The CAG trinucleotide repeats of IT15 gene were examined. The mini mental state examination (MMSE), Montreal cognitive scale (MoCA) were used to evaluate the cognitive function. Hamilton anxiety scale (HAMA), Hamilton Depression scale (HAMD) were used to evaluate the emotion. Activities of daily living scale (ADL) were used to evaluate the ability of daily life. Results Genetic test was conducted on twenty-four individuals from 4 families. Genetic test detected eight HD patients with 41-54 CAG repeats (46.75±4.03) and seven presymptomatic patients with 43~58 CAG repeats (50.00 ±6.40). Four of HD patients required genetic counseling for marriage and childbearing. The number of normal CAG repeats was 12~24, with 17 and 20 being the most common. Correlation analysis found that the number of CAG repeats was negatively correlated with the age of onset (r=-0.967, P＜0.01). ADL score was positively correlated with course of disease (r=0.842, P＜0.01), and negatively correlated with MMSE score (r=-0.930, P＜0.01) and MoCA score (r=-0.932, P＜0.01). Conclusion Genetic test is of great significance in the diagnosis of Huntington's disease, especially in patients with negative family history. The number of CAG repeats is increase from generation to generation and there is genetic anticipation in HD families. The number of CAG repeats can predict the onset age to some extent. Genetic counseling and prenatal diagnosis are important to avoid the birth of a child with HD.

Test-Linked Lectures on Genetic Testing-Related Knowledge for University Festival Visitors: Effectiveness Evaluation / 社会薬学

In this study, we conducted test-linked lectures (using a pre-test and a poster related to the pre-test) to understand the contents of “genetic testing-related knowledge” for university festival visitors. We also assessed their level of understanding and the effectiveness of the lectures pre- and post-test, by dividing the visitors into groups according to gender, medication, and age. First, pharmacy students performed a pre-test (9 questions, each with 4 answer choices) on “flow of genetic information, protein structure and function, relation between gene and protein/living body, basic knowledge of genetic testing and sampling method” for the visitors. Second, lectures were conducted using posters that included the contents of the pre-test. Finally, a post-test was performed with the same content as that of the pre-test. The results revealed a high correct-response rate (more than 65%) for the post-test in most groups (except for some groups with visitors in their 70s). In addition, compared to the overall pre-test scores, those of the post-test showed a significant increase. Thus, we elucidated that test-linked lectures contribute to the comprehension degree improvement in visitors aged from their teens to their 60s ; the validity of lectures using pre-test and poster was also proved.

Regulated sandbox and disease-related genetic tests as a direct-to-consumer test

Recently, the Korean government introduced a regulatory sandbox that includes direct-to-consumer (DTC) genetic tests. Several genetic testing companies received approval for predictive DTC genetic tests for conditions ranging from cancer to chronic diseases. However, it is not evident how DTC tests should be carried out and interpreted. It does not seem to estimate the accuracy of the predictive genetic testing from a two-year exemption trial. However, clinical laboratories can no longer explore innovative approaches to genetic testing because of the restrictive regulatory and legal environment. Genetic testing companies can provide DTC services without restrictions on facilities, equipment, and personnel although those testing services were not fully supported scientifically. Present situation in Korea on DTC genetic test should be reformed.

Pharmacoeconomics Evaluation of CYP2C19 Genetic Test Guiding Antiplatelet Therapy for Acute Coro-nary Syndrome Patients in China / 中国药房

OBJECTIVE:To evaluate the feasibility of using CYP2C19 gene to guide the use of antiplatelet agents in acute cor-onary syndrome(ACS)patients undergoing interventional operation in China from the viewpoint of pharmacoeconomics. METH-ODS:Based on global PLATO trial data,the patients were divided into 3 groups according to treatment strategies(clopidogrel group,ticagrelor group,genetic test group). By applying Treeage Pro 2011 software,short-term decision tree model and long-term Markov model were established,and related data were imported to evaluate cost-effectiveness of different treatment strategies. RE-SULTS&CONCLUSIONS:For ACS patients,according to the level of GDP in China,conventional use of ticagrelor is of pharma-coeconomic advantage for in Shanghai and uninsured patients insured patients;the use of antiplatelet agents guided by CYP2C19 gene test is of pharmacoeconomic advantage among nationwide insured patients.

Pharmacogenomics and Clinical Pharmacists / 医药导报

Pharmacogenomics does not only bring the connection of genes,medicines and diseases,but also become a powerful tool for clinical pharmacists.Pharmacogenomics is commonly used in clinical practice,especially in the implementation of genetic-test results for guiding rational use of medicines.The genotyping results of genes can provide good individualized medication guidance for patients,which can be confirmed by clinical use of the clopidogrel and warfarin.As a member of the clinical treatment team,clinical pharmacists should take advantage of pharmaceutical and pharmacogenomics information to promote rational use of medicines.

Clinical features and genetic analysis of intellectual disability in children with epilepsy of unknown causes / 中华实用儿科临床杂志

Objective To explore the clinical features,genetic causes and prognosis of intellectual disability with epilepsy(ID-E)in children.Methods The data of unknown causes of ID-E children(n=40)who were identified in Department of Pediatrics,Xiangya Hospital of Central South University from March 2015 to March 2016 were respectively analyzed,and follow-up studies were performed to investigate the epilepsy control and intellectual deve-lopment.Results Forty unexplained ID-E included 25(62.5％)male,and 34(85.0％)cases were severe intellectual disability patients.The onset age of epilepsy was 0.16 to 8.00 years old,median age was 1.5 years old.Twenty cases(50.0％)had slow electroencephalogram background,and 22 cases(55.0％)had focal spikes.Ten cases(25.0％)had abnormal cranial images,with brain dysplasia or atrophy.Follow-up lasted from 0.58 to 1.58 years,and 19 cases(47.5％)had seizure control.Twenty-five cases(62.5％)had used at least 2 anti-epilepsy drugs during follow-up,and 19 cases(47.5％)had drug refractory epilepsy.Improvement of mental or motor development in epilepsy controlled group and the uncontrolled group were 12 cases(63.2％)and 2 cases(9.5％).There were separately 8 cases(8/40 cases,20.0％)and 3 cases(3/16 cases,18.8％)diagnosed respectively by whole genome-wide analysis of copy number variants(CNVs)and gene-panel whose CNVs test findings were negative.Conclusions ID-E patients of unknown causes have the following clinical features:they were mostly found in male patients with severe intellectual disability,and drug refractory epilepsy patients have rather high percentage;well controlling of epilepsy is useful for improvement of mental and motor development.Genetic analysis is significant for control and prognosis of ID-E patients,and genome-wide CNVs have high positive rates which can be used as first-tier test to detect genetic etiology of ID-E of unknown cause.

Analysis on Policy and Ethics of Non-Invasive Prenatal Test / 中国医学伦理学

This paper comprehensively reviewed the practice and meanings of non-invasive prenatal test (NIPT) in China and discussed the ethical issues.NIPT,as a step of prenatal diagnosis,brought conflicting values and moral economic influences.Its widely application also imposes higher requirements on policy regulation and lead to some ethical issues,including whether the client really informed consent.Genetic counselling is also crucial before and after the test.However,the subjects,doctors and medical staff have not yet fully prepared.Furthermore,this technique is relatively simple and cheap,and its application relates to many aspects.It is necessary to discuss the influence at the early stage and put forward the ethical issues that need to be paid attention to.Therefore,life ethics expert participation is extremely important,and to some extent will leadfetal and maternal supervision,management and supervision to a new level,especially with the development of NIPT and the application of whole genome sequencing (WGS).

The clinical analysis of Huntington disease：a case study from 12 genetic diagnosis families / 中国神经精神疾病杂志

Objective To investigate the clinical manifestation, inherited pattern and the related factor of Hunting?ton disease families. Method The clinical data from 12 HD families was collected from 2013-2014. Patients received the genetic test and neurological evaluation including motor, cognitive and problem of behavior. Results There were 12 patients having the IT15 gene dynamic mutations, including 1 Juvenile Huntington disease patient and 3 pre-symptomat?ic mutant gene carriers. The average CAG repeats of these patients was between the range of 40 to 60, and the average on?set age ranged from 13 to 54 year-old. Positive family history and genetic anticipation could be observed. Patients pre?sented with different clinical manifestations at the early stage while had typical chorea movements, declined cognitive and psychiatric symptoms at the late stage of the illness. Conclusions There are typical triad symptoms in the late stage but not in the early stage nor pre-symptom stage illness. Clinical manifestation and the neuroimaging are both of great ref?erence value, and the genetic test is essential for final diagnosis.

Bibliometric Analysis of Clinical Molecular Diagnosis Based on SCI Database from 1986 to Aug.2015 / 现代检验医学杂志

Objective To analyze literature distribution and research of clinical molecular diagnosis in recent years using bib-liometric method.Methods The “clinicalmolecular diagnosis”as the topic,the papers related to clinical molecular diagnosis were searched from the database of “Web of Sciences”(from 1986 to 2015.8.31).The resulting papers were analyzed using bibliometric method concerning the paper numbers,countries/districts,institutes,journal distribution,etc.Summary of the times cited and citing papers were also investigated.Results A total of 6 279 papers were obtained from the database,and the annual number of publications and citations increased all the time.United States and West European countries (France, Italy,Germany,England,Spain,etc.)issued the largest number of papers.The mean number of citation and h-index were 16.6 times and 118,respectively.The papers about the usage of clinical molecular diagnosis on disease diagnosis,treatment and prognosis had the most citations.Conclusion Clinical molecular diagnostics technology is in the development stage.It plays a larger role in the diagnosis and treatment of disease.The application of this technology may improve our services lev-el significantly.

Rifampin and increase of warfarin dose: A case report and review of the literature / 中国药学杂志

OBJECTIVE: To report an actual case and doing a review about the interaction of warfarin and rifampin to provide a regimen about the combination of the two drugs. METHODS: Discribed a case and analyzed it, while access to relevant literature review. RESULTS: With concurrent use of rifampin, the dose of warfarin increase to 84 mg · week-1 when targeted INR reached. The available literature suggest that when the two drug concurrent used, warfarin doses may increase for several folds, once discontinue rifampin the warfarin dose should be decreased and more INR tests were needed. CONCLUSION: For patient taking rifampin at the same time, the warfarin dose would increase according to the INR, the genetic test may be helpful; when warfarin is discontinued, the warfarin dose may decrease and INR test may increase to get a efficacy and safety anticoagulation therapy.

Strategy for the Customized Mass Screening of Genetic Sensorineural Hearing Loss in Koreans

Hearing loss is one of the most common sensorineural disorder. More than half of congenital bilateral profound deafness cases have been estimated to be attributed to genetic cause. Identification of genetic cause can provide valuable information. We developed new diagnostic strategy combining phenotype-driven candidate gene approach and targeted exome sequencing to find out the causative mutation of hearing loss. The causative mutation detection rates of this strategy were 78.1% and 54.8% in Korean multiplex families and sporadic severe to profound hearing loss families, respectively. The most frequent causative genes of Korean multiplex families were SLC26A4 and POU3F4. The other causative genes were MRNR1, WFS1, COCH, TECTA, MYO6, COL11A2, EYA4, GJB3, OTOF, STRC, MYO3A, and GJB2. The most frequent causative gene of Korean sporadic severe to profound hearing loss families was SLC26A4 followed by GJB2, CHD7, and CDH23. Based upon the results, the value of this strategy as a diagnostic tool seems to be promising. Although whole genome and exome sequencing have advanced as the development of next-generation sequencing, this new strategy could be a good screening and diagnostic tool to find the causative mutations.

Total intravenous anesthesia in a 10-month-old patient with congenital myotonic dystrophy undergoing endoscopic third ventriculostomy: A case report / 대한마취과학회지

Myotonic dystrophy is a rare genetic disorder characterized by muscle atrophy and weakness. Surgical treatment of this condition poses various problems for the anesthesiologist. We describe the anesthetic management of a 10-month-old infant with congenital myotonic dystrophy, who was scheduled for endoscopic third ventriculostomy under general anesthesia. Anesthesia was induced with thiopental sodium, fentanyl, and vecuronium, and thereafter maintained via continuous infusion of propofol and remifentanil. The train-of-four ratio was monitored throughout the operation, and muscle relaxation was reversed with pyridostigmine and glycopyrrolate at the end of the procedure. We show that total intravenous anesthesia using propofol and remifentanil is a satisfactory anesthetic technique in very young patients with congenital myotonic dystrophy.

Prenatal Genetic Test

Genetic testing has been generalized for the diagnosis of diseases and is an important method of research with advances in the life sciences. In particular, we should give better attention to the genetic test for a fetus. Because the fetus has no autonomy, ethical and social issues can arise. Therefore, appropriate genetic counseling is needed for parents to be informed with the characteristics, natural progress, and possible treatment of a genetic disease, prior to the prenatal genetic test. Physicians should also inform parents how a particular genetic risk factor relates with the likelihood of a disease, in order to assist the parents in making the best decision. Furthermore, the current law for prenatal genetic testing should be approached rationally.

Comparative analysis of the recurrent mutations between Uigur and Han ethnic deaf group in Xinjiang region of China / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the recurrent mutations between Uigur and Han ethnic deaf group in Xinjiang region and determine the relationship between ethnicity and mutations.Method:DNA were extracted from peripheral blood of 125 deaf patients from Urumqi and Korla special educational schools in Xinjiang.Audiologic examinations showed that all patients had severe to profound bilateral sensorineural hearing hoss. The coding region of GJB2 gene, SLC26A4 and mitochondrial DNA target fragments were amplified by polymerase chain reaction(PCR).Mutations in GJB2 gene, SLC26A4IVS7-2 A>G, mtDNA 1494C>T and mtDNA1555 A>G were identified by sequencing analysis.Result:Allelic Frequency of the GJB2 35delG and SLC26A4IVS7-2 A>G mutations in Han deaf students were 7.4%and 10.1%,respectively, whereas not found in Uigur deaf groups.The difference was statistically significant. We did not find significant differences in GJB2 235 delC, 299-300delAT, mtDNA A1555G and C1494T allelic frequency between Uigur and Han students.Conclusion:Prevalence of the recurrent mutations between Uigur and Han ethnic deaf group in Xinjiang has a great diversity.

MLPA Applications in Genetic Testing

Multiplex ligation dependent probe amplification (MLPA) is a PCR-based method to detect gene dosage. Since its introduction, MLPA has been used to test a large number of genes for major deletions or duplications. Genetic testing, as a diagnostic tool for genetic disease, has been used primarily to identify point mutations, including base substitutions and small insertions/deletions, using PCR and sequence analysis. However, it is difficult to identify large deletions or duplications using routine PCR- gel based assays, especially in heterozygotes. The MLPA is a more feasible method for identification of gene dosage than another routine PCR-based methods, and better able to detect deleterious deletions or duplications. In addition to detection of gene dosage, MLPA can be applied to identify methylation patterns of target genes, aneuploidy during prenatal diagnoses, and large deletions or duplications that may be associated with various cancers. The MLPA method offers numerous advantages, as it requires only a small amount of template DNA, is applicable to a wide variety of applications, and is high-throughput. On the other hand, this method suffers from disadvantages including the possibility of false positive results affected by template DNA quality, difficulties identifying SNPs located in probe sequences, and analytical complications in quantitative aspects.

Anesthetic experience for patients with malignant hyperthermia susceptibility determined by molecular genetic test: A report of 2 cases / 대한마취과학회지

Malignant hyperthermia (MH) is a potentially fatal pharmacogenetic disorder manifested as a life threatening hypermetabolic crisis in susceptible individuals following exposure to inhalation anesthetics and to depolarizing muscle relaxants. The preoperative diagnosis of MH susceptibility is difficult. The gold standard for determination of MH susceptibility is the in vitro contracture test. However, it is invasive, requiring skeletal muscle biopsy and is not widely available. Recent advances in genetic testing for mutations that result in MH during anesthesia have helped some genetic test have limitations in clinical application due to the diversity of mutations. In Korea, we found the RYR1 genetic mutation by molecular genetic testing for MH susceptibility in a family for which MH had occurred. Based on the results of genetic testing, we could known MH susceptibility of 2 patients. We believe that the genetic testing for MH can be developed and used with some limitations in clinical settings in Korea.

Assinaturas genéticas no câncer de mama / Genetics signatures at the breast cancer

A heterogeneidade nas apresentações clínica e morfológica do câncer de mama é em grande parte decorrente da sua expressão gênica. O comportamento da neoplasia depende de complexa relação entre centenas ou milhares de genes distintos, atuando por meio de suas respectivas proteínas sobre diferentes etapas do funcionamento celular. A possibilidade de estudo da expressão de múltiplas variáveis, de maneira simultânea, por métodos como microarranjos de DNA e RT-PCR, inaugurou uma nova etapa de conhecimento e manejo do câncer de mama. Quatro grandes classes de câncer mamário nasceram de vários estudos: luminal-A, luminal-B, HER2 e basal-símile. As pesquisas que se seguiram procuraram por padrões de expressão genética relacionados a comportamentos biológicos mais especificos, como o risco de recorrência a distância. Os dados obtidos a partir destes testes potencializam as informações obtidas por meio de variáveis clínicas e anatomopatológicas clássicas. Estudos clínicos prospectivos, alguns em andamento, decidirão quanto à incorporação definitiva destes testes no planejamento terapêutico.

The clinical and morphologic heterogeneity of breast cancer is driven to a large extent by abnormal gene expression within tumors. The behavior of the neoplasia depends on complex relation between hundreds or thousands of distinct genes, acting through its respective proteins on different stages of the cellular functions. The possibility of studying multiple variables simultaneously through methods as DNA microarray and RT-PCR inaugurated a new stage if knowledge and management of the breast cancer. Four major molecular classes of breast cancer emerged from several studies: luminal-A, luminal-B, HER2 and basal-like. The following researches looked fir genetic profile related to more specific biological behavior such as the risk of distant recurrence. The data gathered from these tests augment standard diagnostic and prognostic information obtained from traditional clinical pathological variables. Prospective clinical trials, some in progress, will decide about the definitive incorporation of these tests in the therapeutic planning.