Speed and quality of interbody fusion in porous bioceramic Al2O3 and polyetheretherketone cages for anterior cervical discectomy and fusion: a comparative study.

BACKGROUND: The objective of this prospective randomized monocentric study is to compare the speed and quality of interbody fusion of implanted porous Al2O3 (aluminium oxide) cages with PEEK (polyetheretherketone) cages in ACDF (anterior cervical discectomy and fusion). MATERIALS AND METHODS: A total of 111 patients were enrolled in the study, which was carried out between 2015 and 2021. The 18-month follow-up (FU) was completed in 68 patients with an Al2O3 cage and 35 patients with a PEEK cage in one-level ACDF. Initially, the first evidence (initialization) of fusion was evaluated on computed tomography. Subsequently, interbody fusion was evaluated according to the fusion quality scale, fusion rate and incidence of subsidence. RESULTS: Signs of incipient fusion at 3 months were detected in 22% of cases with the Al2O3 cage and 37.1% with the PEEK cage. At 12-month FU, the fusion rate was 88.2% for Al2O3 and 97.1% for PEEK cages, and at the final FU at 18 months, 92.6% and 100%, respectively. The incidence of subsidence was observed to be 11.8% and 22.9% of cases with Al2O3 and PEEK cages, respectively. CONCLUSIONS: Porous Al2O3 cages demonstrated a lower speed and quality of fusion in comparison with PEEK cages. However, the fusion rate of Al2O3 cages was within the range of published results for various cages. The incidence of subsidence of Al2O3 cages was lower compared to published results. We consider the porous Al2O3 cage as safe for a stand-alone disc replacement in ACDF.

Comparison of drug prescribing before and during the COVID-19 pandemic: A cross-national European study.

PURPOSE: The COVID-19 pandemic had an impact on health care, with disruption to routine clinical care. Our aim was to describe changes in prescription drugs dispensing in the primary and outpatient sectors during the first year of the pandemic across Europe. METHODS: We used routine administrative data on dispensed medicines in eight European countries (five whole countries, three represented by one region each) from January 2017 to March 2021 to compare the first year of the COVID-19 pandemic with the preceding 3 years. RESULTS: In the 10 therapeutic subgroups with the highest dispensed volumes across all countries/regions the relative changes between the COVID-19 period and the year before were mostly of a magnitude similar to changes between previous periods. However, for drugs for obstructive airway diseases the changes in the COVID-19 period were stronger in several countries/regions. In all countries/regions a decrease in dispensed DDDs of antibiotics for systemic use (from -39.4% in Romagna to -14.2% in Scotland) and nasal preparations (from -34.4% in Lithuania to -5.7% in Sweden) was observed. We observed a stockpiling effect in the total market in March 2020 in six countries/regions. In Czechia the observed increase was not significant and in Slovenia volumes increased only after the end of the first lockdown. We found an increase in average therapeutic quantity per pack dispensed, which, however, exceeded 5% only in Slovenia, Germany, and Czechia. CONCLUSIONS: The findings from this first European cross-national comparison show a substantial decrease in dispensed volumes of antibiotics for systemic use in all countries/regions. The results also indicate that the provision of medicines for common chronic conditions was mostly resilient to challenges faced during the pandemic. However, there were notable differences between the countries/regions for some therapeutic areas.

Trends and patterns in EU(7)-PIM prescribing to elderly patients in Germany.

PURPOSE: The aim of this study was to explore patterns and long-term development in prescribing potentially inappropriate medication (PIM) according to the EU(7)-PIM list to elderly patients in Germany. METHODS: We analysed anonymized German claims data. The study population comprised 6.0 million insured individuals at least 65 years old, including all their prescriptions reimbursed in 2019. For the analysis of long-term development, we used data for the years 2009-2019. Factors associated with PIM prescribing were considered from two perspectives: patient-oriented analysis was performed with logistic regression and prescriber-oriented analysis was performed with multiple linear regression. RESULTS: EU(7)-PIM prevalence was reduced from 56.9% in 2009 to 45.1% in 2019. Average annual volume (DDDs/insured) decreased from 145 in 2009 to 121 in 2019. These figures are substantially greater than those for the older PRISCUS list. The majority of investigated ATC level 2 groups with the highest EU(7)-PIM DDD volume exhibited substantial decreases; moderate increases were found for antihypertensive and urological drugs. Antithrombotics increased strongly with the introduction of direct oral anticoagulants. The most prevalent EU(7)-PIM medication was diclofenac; however, in the age group 85+ years, apixaban was twice as prevalent as diclofenac. Polypharmacy, female sex, age < 90 years, need for nursing care and living in Eastern regions were identified as risk factors. Prescriber specialty was the most marked factor in the prescriber-oriented analysis. CONCLUSION: Although the use of EU(7)-PIMs has been declining, regional differences indicate considerable room for improvement. The comparison with PRISCUS highlights the necessity of regular updates of PIM lists.

Potential approaches for the pricing of cancer medicines across Europe to enhance the sustainability of healthcare systems and the implications.

Introduction: There are growing concerns among European health authorities regarding increasing prices for new cancer medicines, prices not necessarily linked to health gain and the implications for the sustainability of their healthcare systems.Areas covered: Narrative discussion principally among payers and their advisers regarding potential approaches to the pricing of new cancer medicines.Expert opinion: A number of potential pricing approaches are discussed including minimum effectiveness levels for new cancer medicines, managed entry agreements, multicriteria decision analyses (MCDAs), differential/tiered pricing, fair pricing models, amortization models as well as de-linkage models. We are likely to see a growth in alternative pricing deliberations in view of ongoing challenges. These include the considerable number of new oncology medicines in development including new gene therapies, new oncology medicines being launched with uncertainty regarding their value, and continued high prices coupled with the extent of confidential discounts for reimbursement. However, balanced against the need for new cancer medicines. This will lead to greater scrutiny over the prices of patent oncology medicines as more standard medicines lose their patent, calls for greater transparency as well as new models including amortization models. We will be monitoring these developments.

Can Aspartate Aminotransferase in the Cerebrospinal Fluid Be a Reliable Predictive Parameter?

Brain ischemia after central nervous system (CNS) bleeding significantly influences the final outcome of patients. Catalytic activities of aspartate aminotransferase (AST) in the cerebrospinal fluid (CSF) to detect brain ischemia were determined in this study. The principal aim of our study was to compare the dynamics of AST in 1956 CSF samples collected from 215 patients within a 3-week period after CNS hemorrhage. We compared concentrations of the AST catalytic activities in the CSF of two patient groups: survivors (Glasgow Outcome Score (GOS) 5-3) and patients in a vegetative state or dead (GOS 2-1). All statistical evaluations were performed using mixed models and the F-test adjusted by Kenward and Roger and the Bonferroni adjustment for multiple tests. The significantly higher catalytic activities of AST in the CSF from patients with the GOS of 2-1 when compared to those who survived (GOS 5-3, p = 0.001) were found immediately after CNS haemorrhage. In the further course of time, the difference even increased (p < 0.001). This study confirmed the key association between early signs of brain damage evidenced as an elevated AST activity and the prediction of the final patient's clinical outcome. The study showed that the level of AST in the CSF could be the relevant diagnostic biomarker of the presence and intensity of brain tissue damage.

Mechanical properties of a biodegradable self-expandable polydioxanone monofilament stent: In vitro force relaxation and its clinical relevance.

Biodegradable stents are promising treatments for many diseases, e.g., coronary artery disease, urethral diseases, tracheal diseases, and esophageal strictures. The mechanical properties of biodegradable stent materials play a key role in the safety and efficacy of treatment. In particular, insufficient creep resistance of the stent material could result in premature stent collapse or narrowing. Commercially available biodegradable self-expandable SX-ELLA stents made of polydioxanone monofilament were tested. A new, simple, and affordable method to measure the shear modulus of tiny viscoelastic wires is presented. The important mechanical parameters of the polydioxanone filament were obtained: the median Young's modulus was [Formula: see text] = 958 (922, 974) MPa and the shear modulus was [Formula: see text] = 357 (185, 387) MPa, resulting in a Poisson's ratio of ν = 0.34. The SX-ELLA stents exhibited significant force relaxation due to the stress relaxation of the polydioxanone monofilament, approximately 19% and 36% 10 min and 48 h after stent application, respectively. However, these results were expected, and the manufacturer and implanting clinician should be aware of the known behavior of these biodegradable materials. If possible, a biodegradable stent should be designed considering therapeutic force rather than initial force. Additionally, new and more advanced biodegradable shape-memory polymers should be considered for future study and use.

Impact of EU risk assessment process and administrative regulations for manufacturers of combined hormonal contraceptive prescribing. An analysis of developments in Germany and the implications.

OBJECTIVE: Combined hormonal contraceptives (CHC) exhibit differing risks for cardiovascular and thrombotic events (VTE). A European referral process confirmed higher VTE risks for 3rd generation gestagens and drospirenone. CHC are now grouped in risk classes (RC) I, II, and III, with RC III having a higher risk than RC I and X (risk not yet known). Marketing authorization holders were obliged to implement pharmacovigilance measures and risk minimization measures including changes of prescribing information. The study assessed whether these activities induced changes in prescription patterns. METHODS: German prescription data for 1.1 million women below 20 years of age were used to analyze the effects of interventions and potential influence factors using logistic regression. Descriptive statistics were calculated for prescriptions for 3.3 million women from January 2011 to March 2016. RESULTS: Shares of RC I and RC X recipients rose substantially over the observation period, while RC III recipient share showed a steady decrease. The referral induced a slightly faster decrease in RC III and increase in RC X. The implementation of pharmacovigilance measures manifested no additional effect. CONCLUSION: The decrease in RC III share already observed before the referral process can be explained with pre-existing discussions around CHC. The effect attributable to the referral was statistically significant, although very small. While evidence for a connection between interventions and prescription change is only indirect, the study shows that routine data are suitable for impact analyses, and monitoring prescribing patterns can be recommended as feedback after regulatory or political interventions. This is being followed up.

Covariate determinants of effective dosing regimens for time-dependent beta-lactam antibiotics for critically ill patients.

AIMS: Critically ill patients undergoing aggressive fluid resuscitation and treated empirically with hydrosoluble time-dependent beta-lactam antibiotics are at risk for sub-therapeutic plasma concentrations. The aim of this study was to assess the impact of two covariates - creatinine clearance (Clcr) and cumulative fluid balance (CFB) on pharmacokinetics/pharmacodynamics (PK/PD) target attainment within a week of treatment with meropenem (ME) or piperacillin/tazobactam (PIP/TZB). METHODS: In this prospective observational pharmacokinetic (PK) study, 18 critically ill patients admitted to a surgical Intensive Care Unit (ICU) were enrolled. The primary PK/PD target was free antibiotic concentrations above MIC at 100% of the dosing interval (100%fT>MIC) to obtain maximum bactericidal activity. Drug concentration was measured using liquid chromatography-tandem mass spectrometry. RESULTS: The treatment of both 8 septic patients with IV extended ME dosing 2 g/3 h q8 h and 10 polytraumatized patients with IV intermittent PIP/TZB dosing 4.0/0.5 g q8 h was monitored. 8/18 patients (44%) manifested augmented renal clearence (ARC) where Clcr ≥130 mL/min/1.73 m2. Maximum changes were reported on days 2-3: the median positive CFB followed by the large median volume of distribution: Vdme=70.3 L (41.9-101.5), Vdpip = 46.8 L (39.7-60.0). 100%fTme>MIC was achieved in all patients on ME (aged ≥60 years), and only in two patients (non-ARC, aged ≥65 years) out of 10 on PIP/TZB. A mixed model analysis revealed positive relationship of CFBpip with Vdpip (P=0.021). CONCLUSION: Assuming that the positive correlation between CFB and Vd exists for piperacillin in the setting of the pathological state, then CFB should predict Vdpip across subjects at each and every time point.

The Use of Complementary and Alternative Medicine by the General Population in the Czech Republic: A Follow-Up Study.

BACKGROUND: The prevalence of complementary and alternative medicine (CAM) ranges between 0.3% and 86% in most highly developed countries. In the Czech Republic, CAM is used by 76% of the general population. Our aim was to examine patterns in CAM use among a representative sample of the general population in the Czech Republic, for 2011 and 2014. MATERIAL AND METHODS: A cross-sectional survey was conducted. A sex-, age- and region-stratified sample of citizens aged 15 years and older was randomly selected from the 2014 voter registration lists (n = 8,395,132). A comparative analysis of data collected in 2011 and 2014 was performed. RESULTS: Overall, 76.0% (N = 1,365) versus 87.0% (N = 1,565) of the respondents reported use of 1 or more CAM modalities during the past 30 days, in 2011 and 2014, respectively (p < 0.001). In both years, the top 4 CAM modalities used were vitamins/minerals, herbal teas, massage, and relaxation. Yoga replaced dietary supplements excluding vitamins/minerals in the 5th position. Nevertheless, only herbal teas (48.0% vs. 53.0%, p = 0.002), massage (20.0% vs. 26.0%, p < 0.001), relaxation (10.0% vs. 19.0%, p < 0.001), and yoga (3.7% vs. 7.1%, p < 0.001) showed a significant increase in use. CONCLUSIONS: The prevalence of CAM use in the Czech Republic is increasing, especially among people who use biological, body- and mind-based CAM therapies. There is a great need to educate students and health care professionals about the efficacy and safety of CAM in order to meet the patients' demands on CAM.

Genotoxic changes in peripheral lymphocytes after therapeutic exposure to crude coal tar and ultraviolet radiation.

AIMS: Goeckerman therapy is based on combined exposure to UV radiation (UVA, UVB) and crude coal tar (PAHs). Some indicators suggest a genotoxic hazard, however, the level of genotoxic risk of the therapy has not yet been investigated sufficiently. This study aims to assesss the genotoxic risk. METHODS: The studied group consisted of patients with chronic stable plaque psoriasis treated by Goeckerman therapy (n = 29). Heparin-treated peripheral blood samples were collected one day before the first treatment and immediately after the last procedure. The lymphocytes were isolated from the blood. The level of genotoxicity was evaluated using an alkaline version of the Comet assay which detects DNA single strand breaks (DNA-SSBs), a neutral version of the Comet assay which detects DNA double strand breaks (DNA-DSBs), and using chromosomal aberrations. RESULTS: The level of DNA-SSBs increased insignificantly (median; Q1-Q3): 1.4 (0.4; 0.1-1.4) vs. 2.5 (0.6; 0.3-2.7) %tDNA (P = 0.11) and the level of DNA-DSBs increased significantly: 7.8 (6.5; 3.4-10.5) vs. 20.7 (19.3; 14.2-24.6) % DNA (P < 0.001). The total number of aberrated cells (P < 0.001) and structurally aberrated cells (P < 0.001) increased significantly. CONCLUSION: The elevated levels of the DNA-DSBs and the chromosomal aberrations in the peripheral lymphocytes indicated a genotoxic hazard. However, the elevated level of the chromosomal abnormalities was below the upper level of the reference range for healthy Czech adults. While, the genotoxic risk appears to be low, Goeckerman treatment represents a further contribution to the lifetime load of genotoxic factors.

Prevalence of Complementary and Alternative Medicine Use in the General Population in the Czech Republic.

BACKGROUND: Prevalence rates of complementary and alternative medicine (CAM) use are still missing for some European countries, especially in the East. Thus, we measured patterns and determinants of CAM use among a representative sample of the general population in the Czech Republic. METHODS: A cross-sectional survey was conducted. A sex-, age- and region-stratified sample of citizens aged 15 and older were randomly selected from voter registration lists (n = 8,639,375). RESULTS: Overall, 76.0% (n = 1,365) of the respondents reported use of one or more CAM modalities during the past 30 days. The top five CAM modalities used were vitamins/minerals (54.6%), herbal remedies (47.8%), massage (19.9%), relaxation techniques (9.5%), and dietary supplements excluding vitamins/minerals (9.2%). Prevention (82.0%) was the primary reason for CAM use. Only 15.9% of CAM users employed it for therapeutic purposes. The most commonly treated ailments were respiratory (35.0%) and musculoskeletal (33.6%) disorders. CONCLUSION: The prevalence of CAM use in the Czech Republic is high, especially among people who apply CAM for self-treatment prior to seeing a doctor. Half of the study population combined CAM with conventional medical treatment, which may result in potential harm to the patient. Healthcare providers as well as the public should be educated about effective and safe use of CAM.

Thermomechanical properties of nickel-titanium closed-coil springs and their implications for clinical practice.

INTRODUCTION: The aim was to study nickel-titanium closed-coil springs in a clinically relevant test setting with respect to the accuracy of the "preactivation" for nickel-titanium closed-coil springs application and whether it is possible to keep activation forces constant during the whole time of treatment. METHODS: We tested 10 types of springs from 5 manufacturers under clinically relevant conditions, allowing us to study the interactions between load and temperature over time. Hystereses were compared using t tests. RESULTS: Springs with a large mechanical hysteresis also showed a large thermal hysteresis. After heating shock, these springs showed intensive force spikes and persistent high loads. Some springs showed negligible thermal and mechanical hysteresis. Such springs never showed any clinically significant persistent high loads. CONCLUSIONS: Springs with a large hysteresis were unable to keep activation forces constant during the whole time of treatment even after any preactivation, and they might cause persistently high loads and possibly overloading. Only springs with minor hysteresis, low temperature dependence of force, and a clinically useful plateau have the following clinical advantages: reduced chair time, optimal rates of tooth movement, reproducible clinical results, and conservation of anchorage.

Effectiveness of a comprehensive lifestyle modification program for asthma patients: a randomized controlled pilot trial.

OBJECTIVE: The aim of the study was to investigate the effectiveness and feasibility of conducting a complementary 8-week comprehensive lifestyle modification program (CLMP) compared to standard care in patients with bronchial asthma over a 6-month period. METHODS: This was a randomized controlled pilot trial with two groups: intervention (N = 15) group and attention-placebo control (N = 14) group. The intervention group received an 8-week CLMP in addition to standard care. Quality of life, asthma control, lung function, reduction of rescue medication, perceived stress, and psychosocial and spiritual status were measured at the end of the intervention and at the 4-month follow-up. RESULTS: In the intervention group, there was a statistically significant difference in the improvements of quality of life, asthma control, lung function, and the reduction of rescue medication intake at both the end of the intervention and at the 4-month follow-up, with no change being observed in the control group. Significant stress reduction and greater psychosocial and spiritual well-being were observed during the 8-week CLMP in the intervention group. At the end of the intervention, the measures of stress and psychological and spiritual well-being reached statistical significance. CONCLUSIONS: Preliminary findings suggest that adding a CLMP to standard care in patients with bronchial asthma offers greater clinical benefit than standard care alone and also suggest that conducting a large randomized clinical trial is feasible.

Tolerability and outcomes of kinetically guided therapy with gentamicin in critically ill neonates during the first week of life: an open-label, prospective study.

BACKGROUND: Aminoglycosides are bactericidal antibiotics used worldwide for the treatment of serious infections in critically ill patients, including neonates. Critically ill neonates constitute a unique challenge in dosing owing to the pathologic alterations that accompany severe illness and the rapidly changing conditions of these patients. OBJECTIVES: The main objective of this study was to analyze the kinetically guided dosage adjustment of gentamicin in neonates critically ill during the first week of life based on plasma concentrations after the first dose and to identify the impact of covariates (eg, fluid intake, body fluid retention) with respect to gestational age (GA). Tolerability of therapy was also assessed. METHODS: This 10-day, open-label, prospective study included neonates critically ill during the first week of life admitted to the neonatal intensive care unit of a children's hospital between January 2006 and July 2009. Hearing and renal assessments were conducted over a 24-month follow-up period. The patients were treated with gentamicin for suspected sepsis, proven sepsis, or pneumonia as an early sign of sepsis. The first and second doses of gentamicin 4 mg/kg were adjusted according to birth weight and GA: group 1 (GA < 34 weeks), 48-hour interdose intervals; group 2 (GA 34-38 weeks), 36 hours; and group 3 (GA > 38 weeks), 24 or 48 hours. Individual pharmacokinetic parameters were estimated after the first dose (given in 30-minute intravenous infusions) using 4 concentrations. Individual pharmacokinetic parameters were estimated by fitting the parameters of a 2-compartment model into 4 concentrations. The last 2 blood samples were taken 30 minutes before the fourth infusion (C(trough,3)) and 1 hour after its start (C(max,4)). Dosing was individualized to reach target ranges for the C(trough,3) (0.5-2.0 mg/L) and C(max,4) (6-10 mg/L) values. If needed, initial dosing was changed after the second dose by adjusting (reducing or increasing) the third and subsequent doses, or by adjusting (prolonging or shortening) the interdose intervals. C(trough,3) and C(max,4) were assessed to determine differences between predicted and assayed values. Fluid retention was registered as the difference between fluid intake and urine output at different intervals related to the first dose per kilogram of birth weight, and from the start of the first infusion (0 hour) to the day of the fourth infusion. The C(max)/minimum inhibitory concentration (MIC) ratio was determined for assessment of optimal response. Tolerability was evaluated during the 24-month follow-up period using renal sonography to screen for nephrocalcinosis and transient evoked otoacoustic emission recordings to evaluate hearing abnormalities. RESULTS: A total of 84 neonates (all white; 53 males, 31 females; birth weight range, 0.8-4.56 kg; GA range, 24-42 weeks) were enrolled in 3 groups: group 1, GA < 34 weeks, n = 27; group 2, GA 34-38 weeks, n = 22; and group 3, GA > 38 weeks, n = 35. The C(max) value detected 1 hour after the start of the first infusion (C(max,1)) reached the target range of 6-10 mg/L in 66 of the 84 neonates (79%). After the initial dose, C(max,1) was variable (%CV, 29%); the failure rate to reach 6 mg/L was 13%. V(d) decreased with GA (r = -0.30, P < 0.01) and achieved mean (SD) rates of 0.51 (0.10), 0.48 (0.13), and 0.40 (0.15) L/kg in groups 1, 2, and 3, respectively. Neither C(max) nor V(d) was correlated with fluid intake relative to the first infusion. Mean gentamicin clearance measured after dose 1 (0.47 [0.23], 0.66 [0.26], and 0.76 [0.32] mL/min/kg) increased with GA (r = 0.45, P < 0.001). The interdose interval was prolonged after the second and subsequent infusions in 8 of 84 neonates (10%) or by decreasing the third dose and subsequent doses in 51 neonates (61%). The target C(max,4) and C(trough,3) values occurred in 63% (22 of 35) and 83% (29 of 35) of full-term patients (GA >38 weeks), respectively. In preterm neonates, the target range for C(max,4) was reached in 11 of 27 patients (41%) in group 1 and 11 of 22 patients (50%) in group 2; for C(trough,3), the target range was reached in 25 patients (93%) in group 1 and in 16 (73%) in group 2. C(trough,3) >2 mg/L was detected in 1 full-term neonate, and gentamicin was withdrawn. Suspected fluid retention within the time period of 0 hour to the day of the fourth infusion was well correlated with actual body weight (r = 0.58, P < 0.001), but it was negatively correlated with C(max,4) (r = -0.25, P = 0.02). Thirteen of the 84 neonates (15%) had confirmed sepsis. C(max)/MIC was >12 except for 2 resistant staphylococcal infections (C(max)/MIC = 0.4); amikacin and vancomycin were substituted for gentamicin in these cases. Clinical signs and laboratory data indicative of suspected sepsis disappeared in 5 to 10 days in 68 of 71 neonates. In 1 neonate, gentamicin was withdrawn after dose 4 because of a high C(trough,3) value. In the 3 remaining neonates, C-reactive protein was decreased >10 days without changing therapy. Two neonates died, 1 of severe hypoxic-ischemic encephalopathy as a consequence of perinatal asphyxia and another of stage IV intraventricular hemorrhage. Transient renal dysfunction attributable to gentamicin was detected in 1 case. No signs of late toxicity (nephrocalcinosis) were found during the second year of follow-up. Two neonates were diagnosed with unilateral hearing loss, a secondary phenomenon of hypoxic-ischemic encephalopathy thought to be related to the severe perinatal asphyxia. CONCLUSIONS: The initial dose of gentamicin 4 mg/kg for these critically ill premature and mature neonates with sepsis during the first week of life was high enough to reach bactericidal C(max,1) within 6-10 mg/L. C(max,1) <6 mg/L occurred in 13% of neonates. The interdose interval modified according to the recommendation resulted in C(trough) values within the target range of 0.5-2.0 mg/L in all but 2 neonates. The kinetically guided maintenance dosing of gentamicin based on plasma concentrations after the first dose should be optimized, taking into account actual body weight. (EudraCT number: 2005-002723-13).