Alarmins and Related Molecules in Elective Surgery.

Surgery is associated with alterations of alarmins' and related molecules' levels. The aim of this study was to investigate which biomarkers are most involved in surgery. The studied group consisted of 58 patients with inguinal or umbilical hernia or cholecystolithiasis and 21 healthy controls for compa-rison. We also added seven acute patients with appendicitis, cholecystitis and incarcerated hernia. Serum concentrations of soluble receptor of advanced glycation end-products (sRAGE), extracellular newly identified receptor for advanced glycation end-products binding protein (EN-RAGE), calprotectin, high mobility group box 1 (HMGB1) and interleukin 6 (IL-6) were analysed by ELISA before and after surgery. Preoperative concentrations of calprotectin were significantly decreased while concentrations of sRAGE were significantly increased in patients compared to controls; the concentrations of EN-RAGE and HMGB1 did not differ significantly. IL-6 levels were undetectable in elective patients preoperatively and in controls. Postoperatively, there was a significant increase of EN-RAGE, calprotectin, HMGB1, and IL-6 and a significant decrease of sRAGE compared to preoperative levels. In acute patients, all tested molecules except for sRAGE were significantly increased preoperatively, and sRAGE was significantly decreased. In contrast, after surgery, we could observe a further increase in IL-6; the other biomarkers did not differ significantly. We can conclude that the concentrations of all tested biomarkers are significantly influenced by elective surgery. The postoperative levels of all tested molecules increase except for sRAGE, whose level is significantly decreased after surgery. In acute states, these molecules are already increased, and the influence of surgery is, apart from IL-6, insignificant.

Pharmacotherapy as major risk factor of falls - analysis of 12 months experience in hospitals in South Bohemia.

This study aimed to analyze the effect of fall risk-increasing drugs (FRIDs) and drug-related factors relative to falls through clinical pharmacy service in hospitalized patients, focusing on the relevance of clinical pharmacist evaluation in the context of physician assessment. A prospective study of inpatient falls was conducted in 2017 retrieving data from 4 hospitals in South Bohemia, Czech Republic. An online database was developed to collect patient and fall-related data, and fall evaluation records. Healthcare professionals classified the overall effect of drugs on falls using Likert scale. Univariate and multivariate correlations were performed with a significance level of p < 0.05. Out of the total 280 falls (mean age of patients 77.0 years), a mean of 2.8 diagnoses with fall-related risk, 8.8 drugs, and 4.1 FRIDs per fall were identified. Incidence of falls decreased quarterly (p < 0.001). Use of FRIDs were positively associated with increasing age (p = 0.007). Clinical pharmacists were more likely to identify pharmacotherapy as the relevant fall-related risk, compared to physicians evaluation (p < 0.001). An increasing total number of prescribed drugs as well as higher number of FRIDs increased the suspicion in both professionals in the context of drug-related causes of falls.

Range of motion after total knee arthroplasty in hemophilic arthropathy.

BACKGROUND: Outcomes of total knee replacement in cases of hemophilic patients are worse than in patients who undergo operations due to osteoarthritis. Previous publications have reported varying rates of complications in hemophilic patients, such as infection and an unsatisfactory range of motion, which have influenced the survival of prostheses. Our retrospective study evaluated the data of hemophilic patients regarding changes in the development of the range of motion. METHODS: The data and clinical outcomes of 72 total knee replacements in 45 patients with hemophilia types A and B were reviewed retrospectively. Patients were operated between 1998 and 2013. All of the patients were systematically followed up to record the range of motion and other parameters before and after surgery. RESULTS: The mean preoperative flexion contracture was 17° ± 11° (range, 0°-40°), and it was 7° ± 12° (range, 0°-60°) postoperatively. The mean flexion of the knee was 73° ± 30° (range, 5°-135°) before the operation and 80° ± 19° (range, 30°-110°) at the last follow-up. The mean range of motion was 56° ± 34° (range, 0°-130°) before the operation and 73° ± 24° (range, 10°-110°) at the last follow-up. CONCLUSIONS: Statistical analysis suggested that the range of motion could be improved until the 9th postoperative week. The patient should be operated on until the flexion contracture reaches 22° to obtain a contracture < 15° postoperatively or until the contracture reaches 12° to obtain less than 5°. The operation generally does not change the flexion of the knee in cases of hemophilic patients, but it reduces the flexion contracture and therefore improves the range.

The impact of C677T and A1298C MTHFR polymorphisms on methotrexate therapeutic response in East Bohemian region rheumatoid arthritis patients.

Some single-nucleotide polymorphisms (SNPs) might be predictive of methotrexate (MTX) therapeutic outcome in rheumatoid arthritis (RA). The aim of this study was to determine whether SNPs in the methylenetetrahydrofolate reductase (MTHFR) gene are predictive of MTX response. Comparison was made using EULAR response criteria and according to the change of DAS28 (∆DAS28) after a 6-month MTX treatment in RA patient cohort. The two SNPs C677T (rs1801133) and A1298C (rs1801131) have been genotyped. A total of 120 patients were enrolled in the study, and all of them fulfilled the American College of Rheumatology 1987 RA criteria and are currently or previously taking MTX oral treatment, either as a monotherapy (n = 65) or in a combination with other disease-modifying antirheumatic drugs (n = 55). Genotyping was performed using qPCR allelic discrimination. We did not found any association of C677T and A1298C genotypes with MTX treatment inefficacy in dominant model (OR 1.23, 95 % CI 0.57-2.65, P = 0.697; and OR 0.98, 95 % CI 0.47-2.14, P = 1.0, respectively), or in recessive and codominant models. However, when ∆DAS28 after a 6-month therapy was used as a measure of treatment efficacy, the 677CT and 1298AC genotypes were found to be significantly associated with less favorable response to MTX (P = 0.025 and P = 0.043, respectively). In addition, even lower ∆DAS28 was determined for double-mutated 677CT-1298AC heterozygotes. It means that a synergistic effect of 677CT and 1298AC genotypes was observed. Nevertheless, the DAS28 baseline was lower here comparing to other genotypes. Unexpectedly, quite the opposite trend-i.e., better response to MTX-was found in genotypes 677CC-1298CC and 677TT-1298AA. It is an intriguing finding, because these double-mutated homozygotes are known for their low MTHFR-specific activity. Global significance was P = 0.013, η (2) = 0.160-i.e., large-size effect. Thus, our data show greater ability of 677CC-1298CC and 677TT-1298AA genotypes to respond to MTX treatment.

Medial calcar of proximal humeral fracture as landmark in restoration of humeral length in case of hemiarthroplasty.

PURPOSE: Several methods to restore the appropriate length of the humerus in the case of proximal humeral fractures treated by hemiarthroplasty have been previously published. Our study evaluates the possibility of using the medial calcar of humerus for humeral length reconstruction not based on preoperative planning. METHODS: Preparations of 320 dry humeral bones were used for the purpose of the study. Points of interest were marked on each bone: the most proximal point of the humeral head, the crest of greater tuberosity, diameters of the head, the anatomical and surgical necks. Proximal parts of bones were then scanned from two angles with a digital camera and all measurements were performed on calibrated photographs. We compared accuracy in humeral length reconstruction using insertion of the pectoralis major and the area of medial calcar where usually a fracture develops. RESULTS: The distance between the top part of the humeral head and the insertion of pectoralis major was 54.1 ± 6.0 mm. The distance between the lateral margin of the anatomical neck and the medial calcar was 51.4 ± 4.3 mm. We compared these data with diameters of the humeral head. CONCLUSIONS: The site of the fracture can be used for the reconstruction of the humeral length with greater accuracy than area of the pectoralis major insertion. We suggest that to obtain the final distance between the lateral margin of the artificial head and medial calcar of the fracture 2-3 mm should be added to the diameter of the head.

Neuropsychological variables and clinical status in anorexia nervosa: relationship between visuospatial memory and central coherence and eating disorder symptom severity.

AIM: To explore the relationship between visuospatial memory, weak central coherence, and eating disorder (ED) symptoms in anorexia nervosa (AN) inpatients. SAMPLE: 31 female AN inpatients. METHODS: Rey complex figure test (RCFT) was used to assess both visuospatial memory and central coherence. RCFT consisted of copy and recall trials. ED symptoms were assessed by The Eating Disorder Examination-Questionnaire (EDE-Q) and The Clinical and Research Inventory for Eating Disorders (CR-EAT). RESULTS: We found a statistically significant negative correlation between recall accuracy and the total EDE-Q score. Furthermore, recall accuracy and recall central coherence significantly negatively correlate with several EDE-Q and CR-EAT scales. CONCLUSIONS: These findings may contribute to a better understanding of cognitive impairments specifically in ED, and to refining interventions aiming at their improvement.

Does sternal body shape reflect family relationships? A study on a genealogically documented Central European osteological sample (19th-20th centuries).

In forensic contexts, sternal anatomical varieties represent useful tools for the identification of an individual, either by comparison of ante-mortem and post-mortem data, or by potential comparison of data from biologically related individuals. Sternal body variation is also used to detect the biological affinity of individuals in bioarchaeology. However, no study has been made available to date on the degree to which the overall shape of the sternal body reflects the degree of biological relatedness. We, therefore, analyzed the sternal body shape of 10 individuals with known genealogical data, members of one family over three generations including inbred individuals (19th-20th centuries, Bohemia, Czech Republic), and a control sample of 12 biologically unrelated individuals. First, closely biologically related individuals were compared with unrelated individuals based on 10 variables expressing the morphological characteristics of the sternum, and then all individuals were compared based on Fourier analysis depending on their degree of relationship. The results showed that there is a greater degree of shape similarity in biologically related individuals than in unrelated individuals, and variability decreases with an increasing degree of relatedness. Inbred individuals showed the lowest sternum-shape distances and degree of variability, while unrelated individuals, showed the highest distances and variability. Moreover, in some cases, the documented relationships were also supported by a similar morphology of the ossified and fused xiphoid process. Thus, sternal shape analysis expands the possibilities for individual identification and the detection of the biological affinity of individuals for both the forensic sciences and bioarchaeology.

Pregnancy-associated plasma protein A as an independent mortality predictor in long-term hemodialysis patients.

BACKGROUND/AIMS: Pregnancy-associated plasma protein A (PAPP-A) is a biomarker related to vascular damage. The aim of the study was to focus on PAPP-A and related parameters and their relationship to the prognosis of long-term hemodialysis (HD) patients. METHODS: This is a prospective observational cohort study which included 261 long-term HD patients followed up for 5 years and 66 healthy subjects. PAPP-A, placental growth factor (PlGF), matrix metalloproteinase 2 and 9 (MMP-2, MMP-9), insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-4 (IGFBP-4), and cardiac, nutritional and inflammatory parameters were measured at the beginning of the study and tested as predictors of mortality. RESULTS: PAPP-A, PlGF, IGF-1, IGFBP-4 and MMP-2 were significantly increased in HD patients compared to controls (PAPP-A 27.6 ± 15.5 mIU/l in HD vs. 9.4 ± 2.5 mIU/l in controls, p < 0.001). Increased PAPP-A was a significant independent predictor of overall mortality and mortality due to infection in the multivariate Cox analysis [HR (95% CI): 1.237 (1.060-1.444), p = 0.007, and 1.416 (1.115-1.798), p = 0.004, per standard deviation, respectively]. PAPP-A was not related to cardiovascular mortality. CONCLUSION: Increased PAPP-A is a significant independent predictor of overall mortality and mortality due to infection but it was not related to cardiovascular mortality in this study.

New methodology of TMB assessment from tissue and liquid biopsy in NSCLC.

Immunotherapy has dramatically influenced and changed therapeutical approach in non-small cell lung cancer (NSCLC) in recent five years. Even though we can reach long-term response to this treatment in approximately 20% of patients with NSCLC, we are still not able to identify this cohort of patients based on predictive biomarkers. In our study we have focused on tumor mutation burden (TMB), one of the potential biomarkers which could predict effectiveness of check-point inhibitors, but has several limitations, especially in multiple approaches to TMB quantification and ununiform threshold. We determined the value of TMB in tumor tissue (tTMB) and blood (bTMB) in 20 patients with early stage NSCLC using original custom gene panel LMB_TMB1. We evaluated various possibilities of TMB calculation and concluded that TMB should be counted from both somatic non-synonymous and synonymous mutations. Considering various factors, we established cut-offs of tTMB in/excluding HLA genes as ≥22 mut/Mb and 12 mut/Mb respectively, and cut-offs of bTMB were defined as ≥21 mut/Mb and ≥5 mut/Mb, respectively. We also observed trend in correlation of somatic mutations in HLA genes with overall survival of patients.

Changes in Beliefs About Post-Transplant Immunosuppressants Over Time and Its Relation to Medication Adherence and Kidney Graft Dysfunction: A Follow-Up Study.

PURPOSE: The main aim was to evaluate the changes in beliefs about immunosuppressants over a 3-year period in patients after kidney transplantation. The second aim was to investigate the relationship between beliefs, medication adherence, and selected clinical outcomes such as graft functioning. PATIENTS AND METHODS: This observational follow-up study was conducted in the outpatient post-transplant clinic at the University Hospital Hradec Kralove in the Czech Republic. Adult patients, at least 4 weeks after kidney transplantation, were invited for the structured interview, which was followed by a self-administered questionnaire survey during their regularly scheduled visits at the clinic. Appropriate paired tests were used to compare two measurements of beliefs about immunosuppressants by BMQ-CZ© in 2016 (baseline) and in 2019 (follow-up). Self-reported adherence was measured by two validated tools (MARS-CZ© and BAASIS©) capturing implementation and discontinuation phases. A generalized linear model was used to investigate the relation between beliefs and the consecutive estimated glomerular filtration rate. RESULTS: The study involved 134 patients. Over time, their perceived treatment necessity beliefs of immunosuppressants decreased, while their treatment-related concerns increased. Overall self-reported non-adherence (ie, taking, dosing and discontinuation of immunosuppressants) was reported by 12% of the patients in both observation periods. In the follow-up period, timing non-adherence was reported by 52 (38.8%) patients. Higher baseline treatment concerns were associated with poor adherence whereas higher baseline treatment necessity beliefs corresponded with better kidney functioning, even after adjusting for age. CONCLUSION: Higher treatment necessity beliefs corresponded with better kidney functioning, whereas higher treatment concerns were related to non-adherence to immunosuppressants at the beginning of the observed period. Still, most patients accepted their medicines that do not come without risk. Nevertheless, decreasing treatment necessity beliefs on one hand, and increasing treatment concerns on the other, should be considered in clinical practice.

Hospital admissions to geriatric ward related to adverse drug events: a cross-sectional study from the Czech Republic.

Background Geriatric patients represent a vulnerable population in terms of adverse drug events (ADEs). Objective The aims of this study were to determine the prevalence and preventability of hospital admissions to a geriatric ward related to ADEs, to identify medications involved in these ADEs and to describe potential preventability aspects of ADE-related admissions. Setting University Hospital Hradec Králové, Czech Republic. Methods This cross-sectional study evaluated acute hospital admissions to the geriatric ward of University Hospital Hradec Králové over a period of nine months (April-December 2017). Medication reviews were performed in order to identify ADE-related hospital admissions. Causality was assessed using the World Health Organization-Uppsala Monitoring Centre criteria. Modified Schumock-Thornton algorithm was used to assess the preventability of ADEs. Main outcome measure 9-month-prevalence of ADE-related hospital admissions. Results A total of 366 hospital admissions were included. The 9-month-prevalence of ADE-related hospital admissions was 11.75% [95% confidence interval 8.45-15.05]. Antithrombotic agents and diuretics represented the most common medication classes associated with ADEs (30.2% each). Electrolyte disturbances and gastrointestinal haemorrhages and ulcerations were the most frequently observed ADEs associated with hospital admission. Out of 43 ADE-related hospitalisations, 23 (53.5%) were considered potentially preventable. Conclusion The contribution of ADEs to hospital admission to the geriatric ward was not negligible. Our results also suggest that 53.5% of identified ADE-related admissions could be potentially prevented. This finding demonstrates just how important the research on the preventability of medication-related hospitalisations is. Further studies and implementations are still needed aiming to minimize the risk of medication-related harm.

Spontaneous reports of adverse drug reactions related to oral anticoagulants in the Czech Republic.

Background Oral anticoagulants are established drugs of choice for the prevention and treatment of thromboembolic events. However, monitoring their safety remains warranted. Objective The aim was to analyze spontaneous reports of adverse drug reactions related to oral anticoagulants in the Czech Republic. Setting Retrospective observational pharmacovigilance study. Methods Adverse drug reaction reports were obtained from the State Institute for Drug Control between January 2005 and November 2017. Reports related to warfarin, dabigatran, apixaban, and rivaroxaban received from healthcare professionals and patients were analyzed. Main outcome measure Frequency and nature of adverse drug reactions reported to oral anticoagulants. Results In total, 297 reports containing 672 adverse drug reactions were received; 269 reports were sent by healthcare professionals (85% by physicians). In 65% of all reports, reactions were due to direct oral anticoagulants. A higher total number of adverse drug reactions was associated with direct oral anticoagulants than with warfarin [reporting odds ratio (ROR): 10.76; confidence interval (CI): 8.70-13.32; p < 0.001]. Along with the increasing utilization of direct oral anticoagulants, the reporting rate gradually declined over time, especially for rivaroxaban and apixaban. Fatal outcomes were reported in 7%, mostly for dabigatran. Hemorrhagic reactions were the most frequently reported adverse drug reactions (37% associated with dabigatran, 28% with apixaban, 24% with warfarin, and 23% with rivaroxaban), and compared to warfarin, they were significantly more often associated with direct oral anticoagulants (ROR: 14.36; CI: 9.57-21.54; p < 0.001). Conclusion The number of adverse drug reaction reports related to oral anticoagulants in the Czech Republic was relatively low, compared to other studies, but 96% of the cases were serious. Data from spontaneous adverse drug reactions reporting should be further analyzed in order to obtain additional information on the safety profile of oral anticoagulants.

Genetic predisposition to advanced glycation end products toxicity is related to prognosis of chronic hemodialysis patients.

BACKGROUND: Advanced glycation end products (AGEs) belong to uremic toxins and some pathological effects of AGEs are linked to RAGE (receptor for AGEs). Their precursors are detoxified by the glyoxalase (GLO) system. The A419C (E111A) polymorphism of the GLO I gene is associated with vascular disease in hemodialysis (HD) patients and some RAGE gene polymorphisms are implicated in various pathological states. AIM: To study the relationship of A419C GLO I and four RAGE polymorphisms (-429T/C, -374T/A, 2184A/G and Gly82Ser) in the prognosis of HD patients. METHODS: The group studied consisted of 214 chronic HD patients prospectively followed up for 43 months. 100 patients died, 48 due to cardiovascular causes. RESULTS: The Kaplan-Meier analysis showed a higher mortality rate in patient-mutated homozygotes for RAGE -429CC, RAGE 2184GG and GLO I 419CC. A higher hazard risk was confirmed by the Cox proportional hazards model when wild-type homozygotes were taken as reference: RAGE -429CC 2.28 (95% CI 1.04-4.99), RAGE 2184GG 3.16 (95% CI 1.44-6.93), and GLO I 419CC 1.75 (95% CI 1.08-2.86). Both RAGE polymorphisms were also associated with cardiovascular mortality: RAGE -429CC 3.54 (95% CI 1.37-9.14) and RAGE 2184GG 5.04 (95% CI 1.93-13.11). CONCLUSION: In summary, our study shows for the first time a link between RAGE and GLO polymorphisms in the prognosis of HD patients.

Attachments of muscles as landmarks for implantation of shoulder hemiarthoplasty in fractures.

BACKGROUND: The attachments of muscles and the position of the humeral head are important for a good functional outcome of shoulder hemiarthroplasties after displaced fractures of the proximal humerus. Deviations in the attachments and changes in their spatial position with respect to the humeral head during surgical reconstruction change the biomechanics and reduce the range of motion of the should joint postoperatively. METHODS AND RESULTS: We used 198 humerus preparations and using 3-dimensional analysis measured the angular relationships between the humeral head axis and medial margin of the greater tuberosity (11.9 degrees +/- 9.1 degrees ), lateral margin of the lesser tuberosity (48.0 degrees +/- 7.8 degrees ), and the crest of the greater tuberosity (27.1 degrees +/- 9.6 degrees ). CONCLUSION: This study provides average values of the positions of the greater and lesser tuberosities with respect to the humeral head axis. We show that the greater and lesser tuberosities are more reliable than the transepicondylar line for reconstruction of humeral head retroversion. LEVEL OF EVIDENCE: Basic Science.

Lesser tuberosity is more reliable than bicipital groove when determining orientation of humeral head in primary shoulder arthroplasty.

PURPOSE: The objective of the study was to provide statistical evaluation of position of bone landmarks of proximal humerus in relation to transepicondylar line and find out which one is the most suitable for setup of the head retroversion in case of humeral head destruction. METHODS: We measured 185 dry humeral preparations (92 left, 93 right). Structures of interest on the proximal humerus were marked with pointers of custom made steel frame. Angular relationships between the humeral head axis and medial margin of the greater tuberosity, lateral margin of the lesser tuberosity, bicipital groove, and crest of the greater tuberosity were evaluated with respect to intramedullary axis of the proximal humeral shaft. RESULTS: The angle between the humeral head axis and medial margin of greater tuberosity was 11.5 +/- 9.0 degrees , the angle between the lateral margin of the lesser tuberosity and the axis was 47.5 +/- 7.4 degrees , the angle between the bicipital groove and the axis was 31.6 +/- 8.8 degrees at the level of the humeral head. The angle between the crest of the greater tuberosity and the axis was 26.6 +/- 9.6 degrees in plane of the surgical neck. CONCLUSIONS: We statistically proved that the lateral margin of lesser tuberosity is more reliable than the bicipital groove; medial margin of the greater and transepicondylar line for reconstruction of humeral head retroversion. We suggest that the lesser tuberosity should be used to determine the retroversion, especially in cases when the margin of humeral head was destructed.

Analysis of the fall-related risk of pharmacotherapy in Czech hospitals: A case control study.

RATIONALE, AIMS, AND OBJECTIVES: Falls are among the major problems occurring in hospital setting, when drugs are viewed as important modifiable risk factor of falling. The aim was to analyse the effect of pharmacotherapy on the risk of falls in hospitalized patients. METHODS: A multicentre prospective case-control study was conducted in 2017 retrieving data from four hospitals in South Bohemia, Czech Republic. An online database was constructed to collect patient and fall-related data. Each fall that occurred during hospitalization was assigned to appropriate controls (no fall during hospitalization) based on gender, age, length of hospitalization, and the number of drugs. Univariate and multivariate correlations were performed with a significance level of P < .05. RESULTS: A total of 222 fall cases (107 males; median age, 81 y) and 1076 controls (516 males; median age, 80 y) were included. According to the first ATC level classification, drugs from groups S, N, and P were significantly associated with fall-related risk compared with controls (P < .05); further analysis of ATC levels showed that only psycholeptics (N05), antipsychotics (N05A), and tiapride were significantly associated with falls. Regression analysis revealed use of psycholeptics N05 (OR = 2.06; 95% CI, 1.56-2.76), or ophthalmologicals S01 (OR = 2.72; 95% CI, 1.37-5.41), as factors with the highest fall-related risk. CONCLUSIONS: Apart from the commonly considered fall-risk increasing drugs, other groups, such as ophthalmologicals, should also be considered; however, regarding clinical practice, it is difficult to evaluate the effects of individual drugs in the context of other risk factors of falls, due to the multifactorial nature of falls.

Atmospheric metal pollution records in the Kovárská Bog (Czech Republic) as an indicator of anthropogenic activities over the last three millennia.

Three peat cores were extracted from the Kovárská Bog in the central Ore Mountains to study anthropogenic pollution generated by mining and metallurgy. The core profiles were 14C dated, and concentrations of selected elements were determined by ICP MS and HG-AAS. Principal component analysis indicated that Pb, Cu, As and Ag may be useful elements for the reconstruction of historical atmospheric pollution. Total and anthropogenic accumulation rates (ARs) of Pb, Cu and As estimated for the last ca. 3500years showed similar chronologies, and revealed twelve periods of elevated ARs of Pb, As and Cu related to possible mining and metallurgic activities. In total, four periods of elevated ARs of Pb, Cu and As were detected during the Middle and Late Bronze Ages, including a distinct Late Bronze Age pollution event between 1030BCE and 910BCE. The Iron Age included three episodes of increased ARs of Pb and As; the first and the most distinctive episode, recorded between 730 and 440BCE, was simultaneous with the Bylany culture during the Hallstatt Period. The Roman Age was characterized by one pollution event, two events were detected in the Middle Ages, and the last two during the modern period. Enhanced element ARs in the late 12th and 15th centuries clearly documented the onset of two periods of intense mining in the Ore Mountains. Metal ARs culminated in ca. 1600CE, and subsequently decreased after the beginning of the Thirty Years' War. The last boom of mining between 1700CE and 1830CE represented the last period of important metallurgical operations. Late Medieval and modern period metal ARs are in good agreement with written documents. Earlier pollution peaks suggest that local metal production could have a much longer tradition than commonly believed; however, archaeological or written evidence is scarce or lacking.

Immunosuppressive therapy related adherence, beliefs and self-management in kidney transplant outpatients.

PURPOSE: Kidney transplant (KTx) recipients should strictly adhere to their lifelong complex therapeutic regimen, and any barriers to medication adherence can weaken correct patient behavior. This study aimed to determine the adherence to immunosuppressive therapy (IS) in KTx adult outpatients in the Czech Republic, and attempted to gain a greater insight into their attitudes toward IS and self-management tasks. MATERIALS AND METHODS: Pharmacist-led structured interviews were conducted to assess self-reported adherence to IS using the Czech version of the Medication Adherence Report Scale, in the context of attitudes toward IS in terms of necessity and concern scale of the Beliefs about Medicines Questionnaire. A specific questionnaire was developed to target IS self-management tasks. Medication records were also reviewed for IS serum levels, reflecting direct adherence measurement. Descriptive statistics were used to calculate adherence and self-management variables, and were analyzed by univariate and multivariate correlations, including the decision-tree method. RESULTS: The interview was completed by 211 (male 123; mean age 55.0±12.4 years, mean time 6.6±5.9 years after KTx) of the total of 235 patients. Full adherence to IS was reported by 173 (82.0%) patients. Most of them had IS serum levels within the therapeutic range, however, cyclosporine was associated with the highest variability (P<0.001). Non-adherence and concerns increased over time after KTx (P<0.05). Despite the more common unintentional non-adherence (P<0.001), relatively high concerns signified the risk of not taking IS as prescribed. Concerns also correlated with the perception of impaired health status (P<0.01), as well as the occurrence of IS-related adverse effects (P<0.001). The patients' awareness of their therapy was insufficient, and main gaps in self-management comprised inadequate sun protection, incorrect administration of IS, and unfamiliarity with the IS name, or their indications. CONCLUSION: Although self-reported adherence to IS therapy was satisfactory, the comprehensive evaluation enabled the detection of greater concerns about IS, as well as underestimated self-management tasks that posttransplant interventions should target in the future.

Correlation of Vitreous Vascular Endothelial Growth Factor and Uric Acid Concentration Using Optical Coherence Tomography in Diabetic Macular Edema.

Purpose. We investigated two factors linked to diabetic macular edema (DME), vitreous and serum levels of vascular endothelial growth factor (VEGF) and uric acid (UA) in patients with DME, and compared the results with changes in optical coherence tomography (OCT) and visual acuity (VA). Methods. A prospective study of 29 eyes, 16 cystoid DME and nonproliferative diabetic retinopathy (DR) and 13 nondiabetic controls. Biochemical analysis of vitreous and serum samples was performed and OCT scans were graded according to central retinal thickness (CRT), cube volume (CV), cube average thickness (CAT), and serous retinal detachment (SRD). Results. In DME group, intravitreal concentrations of VEGF (p < 0.001), UA (p = 0.038), and total protein (p < 0.001) were significantly higher than in control group. In DME subjects, intravitreal UA correlated significantly with intravitreal VEGF (ƍ = 0.559, p = 0.03) but not with total vitreous protein and serum UA. Increased intravitreal VEGF in DME group correlated with increase in CV (ƍ = 0.515/p = 0.041). None of the OCT parameters correlated with the VA. Conclusions. The results suggest that the CV might be assessor of anti-VEGF therapy efficacy. Second, apart from VEGF, the role of UA in the pathogenesis and progression of DR should be considered.

Drug holidays: the most frequent type of noncompliance with calcium plus vitamin D supplementation in persistent patients with osteoporosis.

PURPOSE: All current recommendations include calcium and vitamin D (Ca-D) as an integrated part of osteoporosis treatment. The purpose of this pilot study was to analyze compliance with a fixed combination of Ca-D in women persistent with the treatment. PATIENTS AND METHODS: An observational study was carried out in three osteocenters in the Czech Republic. Women with osteoporosis ≥55 years of age concurrently treated with oral ibandronate were eligible. Compliance was evaluated in a period of 3 months by Medication Event Monitoring System (MEMS), tablet count, and self-report. Nonpersistence was defined as a MEMS-based gap in the use of Ca-D to be 30 days or more. RESULTS: A total of 73 patients were monitored, of which 49 patients were analyzed (target population). Based on MEMS, mean overall compliance was 71%; good compliance (≥80%) was observed in 59% of the patients. As many as 71% of the patients took drug holidays (≥3 consecutive days without intake); overall compliance of these patients was 59% and was slightly lower on Fridays and weekends. Patients without drug holidays were fully compliant (did not omit individual doses). Compliance differed according to daily time at which the patients mostly used the Ca-D. Afternoon/evening takers showed a mean overall compliance of 82% while morning/night takers only 51% (P=0.049). Based on MEMS, tablet count, and self-report, compliance ≥75% was observed in 59%, 100%, and 87% of the patients, respectively. Outcomes obtained by the three methods were not associated with each other. Undesirable concurrent ingestion of Ca-D and ibandronate was present only twice. CONCLUSION: Despite almost perfect self-reported and tablet count-based compliance, MEMS-based compliance was relatively poor. Consecutive supplementation-free days were common; more than two-thirds of the patients took at least one drug holiday. This pilot study showed drug holiday to be the most important type of noncompliance with Ca-D in those who are persistent with the treatment.