Type 2 Diabetes mellitus is a progressive metabolic disease characterized by relative insulin insufficiency and insulin resistance resulting in hyperglycemia. Despite the widespread use of metformin, there is considerable variation in treatment response; with approximately one-third of patients failing to achieve adequate glycemic control. Studies have reported the involvement of single nucleotide polymorphisms and their interactions in genetic pathways i.e., pharmacodynamics and pharmacokinetics. This study aims to investigate the association between 19 pharmacogenetics biomarkers and response to metformin treatment.
MassARRAY panels were designed and optimized by Inqaba Biotechnical Industries, to genotype 19 biomarkers for 140 type 2 diabetic outpatients.
The CT genotype of the rs12752688 polymorphism was significantly associated with increased response to metformin therapy after correction (OR=0.33, 95% CI [0.16–0.68], p-value=0.006). An association was also found between the GA genotype of SLC47A2 rs12943590 and a decreased response to metformin therapy after correction (OR=2.29, 95% CI [1.01–5.21], p-value=0.01).
This is the first study investigating the association between genetic variants and responsiveness to medication for diabetic patients from the indigenous Nguni population in South Africa. It is suggested that rs12752688 and rs12943590 be included in pharmacogenomics profiling systems to individualize metformin therapy for diabetic patients from African populations.
Cytochromes P450 play a role in human drugs metabolic pathways and their genes are among the most variable in humans. The aim of this study was to analyze genotype frequencies of five common polymorphisms of cytochromes P450 in Roma/Gypsy and Czech (non-Roma) population samples with Czech origin.
Roma/Gypsy (n=302) and Czech subjects (n=298) were genotyped for CYP1A2 (rs762551), CYP2A6 (rs4105144), CYP2B6 (rs3745274) and CYP2D6 (rs3892097; rs1065852) polymorphisms using PCR-RFLP or Taqman assay.
We found significant allelic/genotype differences between ethnics in three genes. For rs3745274 polymorphism, there was increased frequency of T allele carriers in Roma in comparison with Czech population (53.1 vs. 43.7%; p=0.02). For rs4105144 (CYP2A6) there was higher frequency of T allele carriers in Roma in comparison with Czech population (68.7 vs. 49.8%; p<0.0001). For rs3892097 (CYP2D6) there was more carriers of the A allele between Roma in comparison with Czech population (39.2 vs. 38.2%; p=0.048). Genotype/allelic frequencies of CYP2D6 (rs1065852) and CYP1A2 (rs762551) variants did not significantly differ between the ethnics.
There were significant differences in allelic/genotype frequencies of some, but not all cytochromes P450 polymorphisms between the Czech Roma/Gypsies and Czech non-Roma subjects.
Valproic acid (VPA) is an anticonvulsant used in several clinical scenarios. VPA has been increasingly associated with intentional or unintentional overdose. In patients presenting with severe VPA overdose, supportive care and airway protection are cornerstones of treatment, while levocarnitine is suggested in patients with hyperammonemia and hemodialysis is recommended in patients with VPA serum concentrations (SC) >1,300 mg/L and presence of cerebral edema or shock. Meropenem is a carbapenem antibiotic with a broad spectrum of activity. The pharmacological interaction between VPA and meropenem is characterized by a rapid decrease in VPA concentrations, which contraindicates concurrent use.
The following case report describes the use of meropenem to enhance the clearance of VPA in the case of severe VPA overdose. A patient with altered mental status was transported to the emergency department (ED) after VPA overdose. Meropenem was prescribed for significant elevated VPA SC. An important decline in SC was observed with short-term meropenem dosing, and an improvement in mental status occurred shortly after administration.
Carbapenem therapy has the potential to be used as last line strategy in the management of severe VPA overdose in patients where SC represent a significant risk of toxicity and clinical symptoms suggest difficulty managing the patient.
Coenzyme Q10 (CoQ10) has many vital functions in human body and its endogenous level can be affected either by various diseases or by administrated drugs. This study reveals the effect of atorvastatin, amlodipine and ethoxidol on the endogenous CoQ10 plasma concentration.
It was determined the total plasma concentration of endogenous CoQ10 in the plasma of 54 healthy individuals and 62 patients with cardiovascular diseases during treatment with various drugs using high performance liquid chromatography with mass spectrometric detection (HPLC-MS/MS).
It was found that CoQ10 plasma concentration in patients is statistically significantly lower (on average −49.0 Δ%) than in practically healthy individuals. The total CoQ10 plasma level in patients receiving atorvastatin in the complex therapy is statistically significantly lower (−15.2 Δ%), and in patients taking amlodipine or ethoxidol is statistically significantly higher (+18.2 and + 20.2 Δ%, respectively) than in patients of control groups (a group of patients who receive the same drugs, except for the studied one).
The study showed that in patients with CVDs treated with various drugs the CoQ10 plasma level is statistically significantly lower than in practically healthy individuals. So, to avoid the adverse reactions connected with low CoQ10 plasma levels, it is recommended to adjust the therapy to maintain its constant level.
Self-esteem is the degree to which the qualities and characteristics contained in one’s self-concept are perceived to be positive. The aim of this study was to evaluate the self-esteem scores in phenylketonuria (PKU) patients on “strict”, “loos” and “off diet”. Sixty PKU patients were divided in three equal groups.
Group a: “on strict”, group b: “on loos” and group c: “off diet”. A special questionnaire for self-esteem scores was created for these patients.
Before psychological support, group a patients demonstrated 6/20 (30%) very high self-esteem, 9/20 (45%) high and 5/25 (25%) moderate. After support 14/20 (70%) were turned to very high, 5/20 (25%) represented high except one whose degrees remained an altered. group b 4/20 (20%) were very high, 7/20 (35%) were high, 3/20 (15%) moderate and the rest of them showed low self-esteem degrees, after support, 10/20 (50%) showed very high, 5/20 (25%) became high, 3/20 (15%) turned to moderate and 2/20 (10%) remained unaltered. Group c, 1/20 (5%) were very high self-esteemed, 7/20 (35%) were high, 6/20 (30%) were moderate and 6/20 (30%) with low self-esteemed, at the end of support, 6/20 (30%) become very high, 8/20 (40%) with high, 4/20 (20.0%), moderate self-esteem whereas the rest were unaltered.
Very high and high self-esteem degrees were demonstrated in patients who follow their PKU diet. Moderate and low self-esteem degrees were predominantly found in patients on loos and or off diet. Psychological supports commonly result in amelioration of self-esteem degrees.
Due to lack of adequate data on tramadol kinetic in relevance of CYP2D6 toxicity, this study was designed to investigate the effect of CYP2D6 phenotype in tramadol poisoning. The saliva, urine and blood samples were taken at the admission time. Consequently, concentration of tramadol and its major metabolites were measured.
A pharmacokinetic and metabolic study was developed in cases of tramadol poisoned (n=96). Cases of tramadol poisoned evidenced seizure, hypertension, dizziness, nausea and vomiting symptoms participated.
Female cases showed higher N-desmethyltramadol (M2) tramadol concentrations than male cases: in urine (40.12 ± 124.53 vs. 7.3 ± 7.13), saliva (16.91 ± 26.03 vs. 5.89 ± 7.02), and blood (1.11 ± 1.56 vs. 0.3 ± 0.38) samples. Significant correlation between blood, saliva, and urine concentrations were found (r = 0.5). Based on the metabolic ratio of O-desmethyltramadol (M1) of male (0.53 ± 0.22) and female (0.43 ± 0.26), poisoning and severe symptoms like seizure in female occurs statistically fewer (13.04%) than in male (50.6%). Assessment of CYP2D6 phenotype showed all of the participants were extensive metabolizers (EM) and their phenotype was associated with clinical symptoms.
According to our results, M1 as a high potent metabolite has an important role in toxicity and the likelihood of poisoning in people with EM phenotype. Finally, tramadol metabolic ratio may justify the cause of various symptoms in human tramadol poisoning.
Haemophilia is a rare hereditary haemorrhagic disease caused by coagulation factor VIII (haemophilia A) or IX (haemophilia B) deficiency. Very few data exist on this disease in Congo. This survey aims to describe the epidemiological and clinical aspects of the children affected.
Materials and methods
A descriptive cross-sectional study was carried out in the haematology department of the Brazzaville University Hospital over a period of two years. Children (under 18 years of age) with haemophilia and with a factor VIII or IX level less than or equal to 30% were identified. The parameters analysed included age, diagnostic delay, type and severity of haemophilia, type and frequency of bleeding manifestations, complications and history of transfusion.
Nineteen patients were identified with an average age at diagnosis of four years. The average time to diagnosis was six years, and the most frequent first known bleeding episode was haemorrhage during circumcision. Family history was found in 14 cases. There were 13 cases of haemophilia A and six cases of haemophilia B. Fourteen cases were severe haemophilia; no mild cases were identified. Haemorrhagic manifestations included haemarthrosis, haematomas and mucocutaneous haemorrhages. The average number of haemorrhagic episodes per year was 12. Haemophilic arthropathy was present at diagnosis in seven cases, with the main location being the knee. The average number of hospitalisations before diagnosis was two. Sixteen patients had been transfused at least once.
Although circumcision is the most frequent first known haemorrhagic manifestation of haemophilia in Congo, patients are often diagnosed late, sometimes with severe osteoarticular complications. Further measures are needed to help ensure early diagnosis and improve care.
Management of haemophilia A requires administration of factor VIII therapy which, for those with severe haemophilia A in the UK, is predominantly self-administered at home in a prophylactic regimen to prevent or minimise bleeding. The UK undertakes a national tendering process every three years to ensure access to current and new therapies at a cost-effective price, through contracting for large volumes from individual suppliers. This means that some products may no longer be available and that new products can enter the UK market at any tendering stage.
In the latest tendering round, in 2018, more than one product was withdrawn from the UK market and a new product (NovoEight®; Novo Nordisk) was added to the prescribing list. This meant people with haemophilia having to change products. The experience of 77 people with haemophilia or their carers who changed treatment products during this process was captured by questionnaires administered by haemophilia nurses from 12 treatment centres. Overall, although people with haemophilia felt that they had little influence in decision making about changing to NovoEight, they were confident with their new treatment including packaging and accessories for administration. This was seen more in those who switched from plasma-derived products where ease of infusion was rated highly. Users’ views of haemophilia treatment should be collected at times of change to identify facilitators and barriers experienced in self-management
Haemophilia is an X-linked congenital bleeding disorder due to deficiency of coagulation factor VIII (in haemophilia A) or factor IX (in haemophilia B) caused by mutations of the respective clotting factor genes. Treatment involves the administration of an appropriate dose of factor concentrate, as soon as possible, in the event of any bleeding episode. In low-resource settings, such as Northeast India, where factor concentrates are not widely available, people with haemophilia (PwH) may bleed profusely even from trivial external injuries, warranting transfusion of blood or blood products. We previously reported on the use of a low cost, foam-based haemostatic patch to treat an external bleed in a single patient. In this study, we investigated its use to treat a range of external injuries in PwH presenting at Assam Medical College and Hospital.
Over 24 months, eligible PwH with external injuries attending our haemophilia clinic were treated with a topical haemostatic patch (VELSEAL-T) at the target bleeding site. The time to cessation of bleeding was recorded and the wound sites evaluated after haemostasis to monitor efficacy and safety.
Out of 72 individuals with bleeding disorders who volunteered to participate, 59 cases of external bleeding in 48 PwH were eligible for inclusion in the study. Nine (15.3%) had aberration wounds, 24 (40.7%) cut wounds, 21 (35.6%) tooth and/or gum bleeding and five (8.4%) bleeding from puncture wounds. The average time required for achievement of haemostasis was 9.9 (±4.7) minutes. Aberration wounds required the least amount of time for haemostasis at 7.3 (±4.4) minutes. Cut wounds required a mean time of 8.5 (±2.9) minutes; puncture wounds required 9.0 (±3.1) minutes; gum bleeding required the longest time to achieve haemostasis with a mean of 12.7 (±5.6) minutes.
The use of this topical haemostatic patch has been shown to be beneficial in the treatment of external injuries in PwH, and provides a good treatment option in resource-constrained areas. A larger controlled study would be helpful to further investigate its efficacy and safety.
Haemophilia nurses in the UK are instrumental in supporting people with haemophilia in self-management, including managing treatment options, recording treatment use and understanding the budgetary impact of prescribing practice. The widespread use of prophylaxis identified haemophilia as a high cost disorder to treat, resulting in a financially successful national tendering process with increased scrutiny of clotting factor use at both individual and haemophilia treatment centre level. The UK tenders, undertaken at a national level every three years, have ensured access to current and new therapies at the most cost-effective price through economies of scale in committing to purchase large volumes from suppliers.
In the 2018 tendering round, NovoEight® (NovoNordisk) was added to the prescribing list and other recombinant factors were withdrawn, resulting in changes in prescribing for individual people with haemophilia. This ‘switching’ process is not uncommon in the UK, where national tenders have been in place since 2004. However, the unseen additional workload for nurses, driven by the demands of timely switching to meet product volumes and contracts, has never been captured. During the 2018 switch we interviewed 11 nurses and one operational manager from haemophilia centres across the UK to identify the barriers and facilitators to instigating this change.
Ultimately the switching was completed in a timely manner, demonstrating significant cost reductions for factor concentrates. The unseen workload of the nurse – identifying which patients should have their product switched, discussion with and education of patients/families, adjusting prescriptions for home delivery of clotting factor concentrates and stock management and control to avoid waste, and organising the necessary additional clinic visits – was identified and costed based on salary per hour. Nurses remained positive that they were able to undertake this additional role but recognised that, with no specific national guidance regarding product choice, there may have inevitably been differences in approach between treatment centres.