Karolina Kłoda

Implementing training and support, financial reimbursement, and referral to an internet-based brief advice program to improve the early identification of hazardous and harmful alcohol consumption in primary care (ODHIN) : study protocol for a cluster randomized factorial trial

BackgroundThe European level of alcohol consumption, and the subsequent burden of disease, is high compared to the rest of the world. While screening and brief interventions in primary healthcare are cost-effective, in most countries they have hardly been implemented in routine primary healthcare. In this study, we aim to examine the effectiveness and efficiency of three implementation interventions that have been chosen to address key barriers for improvement: training and support to address lack of knowledge and motivation in healthcare providers; financial reimbursement to compensate the time investment; and internet-based counselling to reduce workload for primary care providers.Methods/designIn a cluster randomized factorial trial, data from Catalan, English, Netherlands, Polish, and Swedish primary healthcare units will be collected on screening and brief advice rates for hazardous and harmful alcohol consumption. The three implementation strategies will be provided separately and in combination in a total of seven intervention groups and compared with a treatment as usual control group. Screening and brief intervention activities will be measured at baseline, during 12 weeks and after six months. Process measures include health professionals’ role security and therapeutic commitment of the participating providers (SAAPPQ questionnaire). A total of 120 primary healthcare units will be included, equally distributed over the five countries. Both intention to treat and per protocol analyses are planned to determine intervention effectiveness, using random coefficient regression modelling.DiscussionEffective interventions to implement screening and brief interventions for hazardous alcohol use are urgently required. This international multi-centre trial will provide evidence to guide decision makers.Trial registrationClinicalTrials.gov. Trial identifier: NCT01501552

Professional's Attitudes Do Not Influence Screening and Brief Interventions Rates for Hazardous and Harmful Drinkers: Results from ODHIN Study

AIMS To determine the relation between existing levels of alcohol screening and brief intervention rates in five European jurisdictions and role security and therapeutic commitment by the participating primary healthcare professionals. METHODS Health care professionals consisting of, 409 GPs, 282 nurses and 55 other staff including psychologists, social workers and nurse aids from 120 primary health care centres participated in a cross-sectional 4-week survey. The participants registered all screening and brief intervention activities as part of their normal routine. The participants also completed the Shortened Alcohol and Alcohol Problems Perception Questionnaire (SAAPPQ), which measure role security and therapeutic commitment. RESULTS The only significant but small relationship was found between role security and screening rate in a multilevel logistic regression analysis adjusted for occupation of the provider, number of eligible patients and the random effects of jurisdictions and primary health care units (PHCU). No significant relationship was found between role security and brief intervention rate nor between therapeutic commitment and screening rate/brief intervention rate. The proportion of patients screened varied across jurisdictions between 2 and 10%. CONCLUSION The findings show that the studied factors (role security and therapeutic commitment) are not of great importance for alcohol screening and BI rates. Given the fact that screening and brief intervention implementation rate has not changed much in the last decade in spite of increased policy emphasis, training initiatives and more research being published, this raises a question about what else is needed to enhance implementation.

Association between low-dose folic acid supplementation and blood lipids concentrations in male and female subjects with atherosclerosis risk factors.

Background Folic acid (FA) is one of the B complex vitamins. It is thought that FA deficiency promotes atherosclerosis formation in arterial endothelium. FA, acting through reducing homocysteine (Hcy) levels, may contribute to decreased cholesterol (Ch) synthesis. The aim of this study was to analyze the association of low-dose folic acid supplementation with blood lipids concentrations in subjects with atherosclerosis risk factors. Material/Methods The study enrolled 124 Caucasian individuals (60 M, ages 20–39; and 64 F, ages 19–39) with atherosclerosis risk factors (family history of premature ischemic stroke, arterial hypertension, dyslipidemia, overweight and obesity, cigarette smoking, and low level of physical activity). The participants were asked to take FA at a low dose of 0.4 mg/24 h for 12 weeks. Results FA levels increased in females (6.3 vs. 12.5 ng/dL; p=0.001) and males (6.4 vs. 11.4 ng/dL; p=0.001) and Hcy levels decreased (10.6 vs. 8.3 μmol/L; p=0.001 and 11.5 vs. 9.3; p=0.001, respectively). A significant reduction in mean concentration of total cholesterol in females (203.4 vs. 193.1 mg/dL; p=0.001) and in males (209.5 vs. 201.9; p=0.002) was observed. The low-density lipoprotein cholesterol (LDL-C) levels decreased in females and in males (107.4 vs. 99.9 mg/dL; p=0.001 and 121.5 vs. 115.1; p=0.002, respectively). The apoAI concentrations increased in smoking women and in men with BMI ≥25 kg/m2 (p=0.032 and p=0.024, respectively). Conclusions Low-dose FA supplementation has a beneficial effect on blood lipids through decreasing concentrations of total cholesterol and LDL-C and increasing concentrations of apoAI.

The impact of CTLA4 and PTPN22 genes polymorphisms on long-term renal allograft function and transplant outcomes

Abstract Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) downregulates the immune system. Lymphoid tyrosine phosphatase (Lyp)—PTPN22 protein—is suggested to be negative regulator of T-cell reaction. There are several polymorphisms in the CTLA4 and PTPN22 genes, which can influence the immune response and allograft function after kidney transplantation. The aim of this study was to examine the impact of CTLA4 and PTPN22 genes polymorphisms on the long-term renal transplant function and recipients’ outcomes during a 5-year follow-up observation. The study enrolled 268 Caucasian renal transplant recipients. Genotyping of the rs231775 (+49AG) CTLA4 gene polymorphism was performed using real-time PCR and rs2476601 (C1858T) PTPN22 gene polymorphism using PCR-RFLP method. The 5-year graft survival rate was 81.7%. Dialysis was necessary in 22 (8%) patients, 7 (2.6%) patients died and 20 (7.4%) switched to another transplantation center. We found no association between studied polymorphisms and graft loss/dialysis. Comparison of the distribution of the +49AG CTLA4 and C1858T PTPN22 genes polymorphisms genotypes among dead and living patients showed no statistically significant differences. Above results suggest that the rs231775 (+49AG) CTLA4 and rs2476601 (C1858T) PTPN22 genes polymorphisms are not associated with long-term allograft failure, graft loss and mortality after transplantation.

The impact of ICAM1 and VCAM1 gene polymorphisms on long-term renal transplant function and recipient outcomes.

BACKGROUND Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are implicated in endothelial cell-leukocyte adhesion. Several functional polymorphisms that affect the expression of ICAM-1 and VCAM-1, and therefore post-transplant immunological response, have been found in genes of these molecules. The aim of this study was to examine the impact of ICAM1 and VCAM1 gene polymorphisms on long-term renal transplant function and recipient outcome during a 5-year follow-up period. MATERIAL AND METHODS The study enrolled 269 Caucasian renal transplant recipients (165 males, 104 females, mean age 47.58 ± 12.96 years) remaining under observation for 5 years. Genotyping of the c.1405A>G (Lys469Glu, rs5498) ICAM1, T(-1592)C (rs1041163), and T(-833)C (rs3170794) VCAM1 genes polymorphisms was performed using real-time PCR. RESULTS The rs5498 ICAM1 GG genotype was an independent risk factor associated with increased creatinine concentration at 12, 24, 36, 48, and 60 months after transplantation (p=0.0004, p=0.02, p=0.01, p=0.01 and p=0.04, respectively). Creatinine concentrations 36 and 48 months after transplantation were higher among CC homozygotes of the rs1041163 VCAM1 (TT+CT vs. CC, p=0.049 and p=0.04, respectively). The C allele of the rs1041163 VCAM1 gene polymorphism was identified as a risk factor for dialysis after transplantation (HR=3.323, 95%CI=1.44-7.67, p=0.005). The C allele of the rs1041163 VCAM1 gene was at the border of statistical significance as a risk factor for death after transplantation (p=0.06). CONCLUSIONS These results suggest that the rs5498 ICAM1 GG genotype is correlated with early and long-term allograft failure. The C allele of the rs1041163 VCAM1 gene may be associated with long-term allograft failure and graft loss, as well as increased morbidity after transplantation.

Correlation between ICAM1 and VCAM1 gene polymorphisms and histopathological changes in kidney allograft biopsies

Introduction The immunoglobulin-like molecules intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) are responsible for endothelial cell-leukocyte adhesion followed by transmigration of leukocytes through the endothelial cell lining. The aim of this study was to examine the correlation between polymorphisms in ICAM1 and VCAM1 genes and histopathological changes in transplanted kidney biopsies. Material and methods The study enrolled 82 Caucasian renal transplant recipients (48 males, 34 females). Genotyping of the rs5498 ICAM1 and the rs1041163 and rs3170794 VCAM1 gene polymorphisms was performed using real-time polymerase chain reaction (PCR). Biopsies were performed in 82 patients and were reviewed by a renal pathologist and the Banff working classification criteria were used. Results There were no significant associations between VCAM gene polymorphisms and histopathological changes in kidney allograft biopsies. ICAM1 gene polymorphism was associated with the grade of interstitial fibrosis. Interstitial fibrosis was more severe among individuals with the G allele than those with the A allele (AA vs. GG+AG, p = 0.017). There were no statistically significant associations between ICAM1 gene polymorphism and other histopathological changes in kidney allograft biopsies. Conclusions The results of our study suggest that rs5498 ICAM1 gene polymorphism is associated with the grade of interstitial fibrosis in kidney recipients and the changes are more severe in patients with the G allele.

Is there an effect of folic acid supplementation on the coagulation factors and C-reactive protein concentrations in subjects with atherosclerosis risk factors?

INTRODUCTION Folic acid (FA) may delay the formation of atherosclerotic lesions. Increased plasma levels of von Willebrand factor (VWF) are observed in cardiovascular disease, which leads to higher risk of thrombosis. Fibrinogen (Fb) is a well-documented risk factor of cardiovascular disease. The aim of this study was to analyze the effect of FA supplementation on the Fb, VWF and C-reactive protein (CRP) plasma concentrations in subjects with atherosclerosis risk factors. MATERIAL/METHODS The study enrolled 124 Caucasian individuals (60 M, 64 F) with atherosclerosis risk factors--family history of premature ischaemic stroke, arterial hypertension, dyslipidaemia, overweight and obesity, cigarette smoking and low physical activity. The participants were asked to take FA in the low dose of 0.4 mg/24 h for three months. RESULTS After FA supplementation a significant reduction of the VWF concentrations in females (76.6 vs 72.3%; p=0.028) and in males (75.5 vs 66.9%; p=0.001) was observed. Among women and men with dyslipidaemia concentrations of VWF decreased after FA supplementation (76.8% vs 69.6%; p=0.003 and 76.7% vs 67.8%; p=0.001 respectively). Among females and males with BMI ≥25 kg/m² concentrations of VWF decreased only in men (77.6% vs 66.5%; p=0.001). In female and male smokers supplementation of FA decreased VWF concentrations (82.5% vs 74.4%; p=0.012 and 76.6% vs 69.5%; p=0.036 respectively). DISCUSSION The results of our study suggest that there is an effect of FA supplementation on VWF concentrations in subjects with atherosclerosis risk factors.

Influence of folic acid supplementation on coagulation, inflammatory, lipid, and kidney function parameters in subjects with low and moderate content of folic acid in the diet

BACKGROUND The human body requires folic acid (FA) to produce blood cells, secure cell division, and growth. Moreover, this vitamin is important in the prevention of cardiovascular disease (CVD). Because the results of studies on the use of FA in the prevention of CVD are ambiguous, it seems necessary to conduct further research, which will explain in which cases supplementation is effective. AIM To assess the impact of FA supplementation on the coagulation, inflammatory, lipid parameters, and kidney function in subjects with atherosclerosis risk factors, depending on the content of FA in their diet. METHODS The study enrolled 97 young adult Caucasian individuals (34 males and 63 females) with atherosclerosis risk factors. This population was divided into two groups: A--with low content of FA in the diet (< 40% of reference daily intake) and B--with moderate content of FA in the diet (40-90% of reference daily intake). The participants were asked to take FA in the low-dose of 0.4 mg/24 h for 3 months. RESULTS Low-dose FA supplementation resulted in elevation of FA concentrations (79% vs. 75.1%) in the studied groups and, concomitantly, a decrease in homocysteine concentrations (21% vs. 20.3%). Mean level of creatinine decreased after FA supplementation in both groups (0.93 ± 1.1 vs. 0.72 ± 0.15 mg/dL and 0.83 ± 0.16 vs. 0.77 ± 0.15 mg/dL). These differences were statistically significant (p < 0.0001). The difference in mean estimated glomerular filtration rate values before and after FA supplementation was statistically significant in group A (p = 0.002) and on the border of statistical significance in group B (p = 0.06). CONCLUSIONS FA supplementation has no influence on the coagulation, inflammatory and lipid parameters in subjects with atherosclerosis risk factors depending on the content of FA in their diet. However FA supplementation may have a beneficial effect on kidney function in subjects with low content of FA in the diet.

Telomere Length Assessment for Prediction of Organ Transplantation Outcome. Future or Failure: A Review of the Literature

Telomeres are located at each end of eukaryotic chromosomes. Their functional role is genomic stability maintenance. The protective role of telomeres depends on various factors, including number of nucleotides repeats, telomere-binding proteins, and telomerase activity. Organ transplantation is the preferred replacement therapy in the case of chronic kidney disease and the only possibility of sustaining recipients’ life in the case of advanced liver failure. While the prevalence of acute rejection is constantly decreasing, prevention of transplanted organ long-term function loss is still challenging. It has been demonstrated that post-transplant stressors accelerate aging of the allografts manifested through telomere shortening. The aim of this paper was to evaluate the importance of telomere length assessment for prediction of organ transplantation outcome. Literature review included the 10 most important studies regarding linkage between allograft function and telomere erosion, including 2 of our own reports. Telomere length assessment is useful to predict organ transplantation outcome. The importance of telomere length as a prediction marker depends on the analyzed material. To obtain reliable results, both graft cells (donor material) and lymphocytes (recipient material) should be examined. In the case of kidney transplantation, assessment of telomere length in the early post-transplant period allows prediction of the long-term function of the transplanted organ. To increase the accuracy of transplantation outcome prediction, telomere length assessment should be combined with evaluation of other aging biomarkers, like CDKN2A (p16). Large-scale clinical studies regarding telomere length measurement, including genome wide association analysis introducing relevant genetic factors, are needed for the future.

Attitudes and Learning through Practice Are Key to Delivering Brief Interventions for Heavy Drinking in Primary Health Care: Analyses from the ODHIN Five Country Cluster Randomized Factorial Trial

In this paper, we test path models that study the interrelations between primary health care provider attitudes towards working with drinkers, their screening and brief advice activity, and their receipt of training and support and financial reimbursement. Study participants were 756 primary health care providers from 120 primary health care units (PHCUs) in different locations throughout Catalonia, England, The Netherlands, Poland, and Sweden. Our interventions were training and support and financial reimbursement to providers. Our design was a randomized factorial trial with baseline measurement period, 12-week implementation period, and 9-month follow-up measurement period. Our outcome measures were: attitudes of individual providers in working with drinkers as measured by the Short Alcohol and Alcohol Problems Perception Questionnaire; and the proportion of consulting adult patients (age 18+ years) who screened positive and were given advice to reduce their alcohol consumption (intervention activity). We found that more positive attitudes were associated with higher intervention activity, and higher intervention activity was then associated with more positive attitudes. Training and support was associated with both positive changes in attitudes and higher intervention activity. Financial reimbursement was associated with more positive attitudes through its impact on higher intervention activity. We conclude that improving primary health care providers’ screening and brief advice activity for heavy drinking requires a combination of training and support and on-the-job experience of actually delivering screening and brief advice activity.