Pharmacokinetics of JNJ-73763989 and JNJ-56136379 (Bersacapavir) in Participants With Moderate Hepatic Impairment.

JNJ-73763989 is comprised of 2 short interfering RNAs (siRNAs), JNJ-73763976 and JNJ-73763924, that target hepatitis B virus (HBV) mRNAs for degradation, thereby inhibiting HBV replication. JNJ-56136379 is a capsid assembly modulator that inhibits HBV replication by inducing the formation of empty capsids (CAM-E). In 2 phase 1, open-label, non-randomized, single-center studies, the single-dose pharmacokinetics, safety, and tolerability of JNJ-73763989 or JNJ-56136379 were assessed in participants with moderate hepatic impairment (Child-Pugh Class B) versus participants with normal liver function. Participants in both studies received a single subcutaneous dose of JNJ-73763989 200 mg or oral JNJ-56136379 250 mg, followed by an evaluation of plasma pharmacokinetic parameters and safety assessments. Plasma exposure to JNJ-73763976, JNJ-73763924, and JNJ-56136379 was 1.3- to 1.4-, 1.8- to 2.2-, and 1.1- to 1.3-fold higher in participants with moderate hepatic impairment versus participants with normal liver function; however, these increases were not considered clinically relevant. Both drugs were well tolerated and safe, with 7 (21.9%) participants experiencing 1 or more treatment-emergent adverse events, 3 of which were related to JNJ-56136379. Overall, the plasma exposures of JNJ-73763989 and JNJ-56136379 were higher in participants with moderate hepatic impairment, but both were well tolerated. Further studies are needed to evaluate the effect of hepatic impairment under multiple-dose administration.

Neutrophil to lymphocyte ratio (NLR) impact on the progression-free survival and overall survival of multiple myeloma patients treated with high-dose chemotherapy and autologous stem cell transplantation.

High-dose chemotherapy with autologous stem-cell transplantation (ASCT) remains the standard of care in multiple myeloma (MM) patients. This retrospective study aimed to assess the impact of neutrophil-to-lymphocyte ratio (NLR) and other complete blood count (CBC)-based predictors on PFS and OS of transplant-eligible MM patients. The CBC-based biomarkers were evaluated in a single-center cohort of 176 MM patients at three time points: at the diagnosis, the time of ASCT, and +100 d after ASCT. Univariable and multivariable Cox's regression analyses and Kaplan-Meier estimate were used in statistical analysis. NLR at ASCT (HR 1.15, 95% CI: 1.05-1.26) and hemoglobin at ASCT (HR 0.80, 95% CI: 0.68-0.94) were independent factors influencing PFS. In the model for OS, the only statistically significant factors were NLR at ASCT (HR 1.15, 95% CI: 1.04-1.27), bortezomib administration prior to ASCT (HR 0.52, 95% CI: 0.33-0.83) and age at diagnosis (HR 1.03, 95% CI: 1.00-1.06). NLR at ASCT is an independent predictive factor in MM patients undergoing ASCT.

Somatic comorbidity in Polish patients with epilepsy.

INTRODUCTION A wide spectrum of somatic and psychiatric disorders occurs frequently in patients with epilepsy, which adds to the burden of this disease. OBJECTIVES The aim of the study was to estimate the prevalence and risk factors of somatic comorbidities and analyze somatic comedication in adult patients with epilepsy. PATIENTS AND METHODS This study involved patients with epilepsy treated in university epilepsy clinic. Data on epilepsy, antiepileptic drugs (AEDs), somatic comorbidities, and their treatment were collected from a structured interview and from medical records. RESULTS The sample population consisted of 636 patients (mean age, 35.3 years); 380 (59.7%) were female and 241 (37.9%) had well­controlled epilepsy. At least 1 comorbid somatic condition was found in 216 patients (34%). The most prevalent somatic comorbidities were cardiovascular diseases, allergies, migraine, hyperlipidemia, thyroid disorders, and chronic lower respiratory diseases. Furthermore, 200 patients (31.4%) were prescribed at least 1 medication for somatic disorders. Logistic regression analysis revealed several independent risk factors for the occurrence of somatic comorbidities: older age, shorter duration of epilepsy, lower seizure frequency, and lower number of AEDs. CONCLUSIONS Somatic comorbidities and comedication with non­AEDs were found in one­third of the relatively young cohort of adult patients with epilepsy. Patients with pharmacoresistant epilepsy may be at risk of underdiagnosis and undertreatment of somatic comorbidities. The presence of comorbidities may have implications for the diagnosis and treatment of seizure disorder and coexisting condition.

Psychiatric comedication in patients with epilepsy.

Psychiatric disorders are more common in patients with epilepsy than in the general population. The aims of the study were to assess the frequency and type of psychotropic drug usage in patients with epilepsy, to assess the risk factors for their use, and to assess their proconvulsive potential and the risk of interactions with antiepileptic drugs. This 20-month prospective study included patients treated at the university hospital outpatient clinic. Psychotropic drugs have been classified according to the Anatomical Therapeutic Chemical Classification System. Of the 621 patients (with a mean age of 35.4years), 60% were women, and 37.5% were in remission; 54.8% of the patients used antiepileptic drug monotherapy. The most commonly used antiepileptic drugs were valproate, levetiracetam, lamotrigine, and carbamazepine. Eighty-nine (14.3%) patients received psychiatric comedication. Sertraline, perazine, and hydroxyzine were the predominantly used psychotropic drugs. Independent variables associated with psychotropic drug usage in the logistic regression model included age, active epilepsy, combined focal and generalized epilepsy type, use of somatic comedication, and phenobarbital. Over one-third of the patients simultaneously received antiepileptic drugs and psychotropic drugs, between which clinically significant interactions may occur, 10% of patients used psychotropic drugs to lower the seizure threshold. The results of the study indicate the need for closer cooperation between doctors of various specialties when caring for patients with epilepsy.

Effect of chemical surface treatment of titanium on its bond with dental ceramics.

STATEMENT OF PROBLEM: Airborne-particle abrasion of titanium is a clinically accepted method of surface preparation. As a side effect of airborne-particle abrasion, particles of the abrasive material get embedded into the surface. How particle presence or removal from the titanium surface affects the strength of the titanium-ceramic bond is unclear. PURPOSE: The purpose of this in vitro study was to determine the effect of removing Al2O3 particles embedded into the surface by means of chemical surface treatment on the strength of the titanium-ceramic bond. MATERIAL AND METHODS: Titanium (TritanCpTi 1, Dentaurum, 99.5% Ti) disks were airborne-particle abraded with 110 µm Al2O3 at a pressure of 0.4 MPa and an angle of approximately 45 degrees. The surface was etched chemically using 1 of 8 reagents, and the veneering ceramic applied and fired. The strength of the metal-ceramic bond was determined using the shear strength test. Further, the effect of thermal fatigue on the bond strength was evaluated. The results were analyzed with 2-way ANOVA and the Tukey honest significant difference (HSD) test (α=.05). Fractographic investigations and microscopic tests were also performed to determine the quality of the titanium-ceramic bond. RESULTS: Effective etching of the titanium surface and removal of Al2O3 particles included a 30% water solution of HNO3 + 3% HF, a mixture of HNO3 + HF + glycerin, a 4% solution of HF in H2O2, and a 4% solution of HF in H2O. A statistically significant difference (of about 50%) in bond strength was found between the groups subjected to chemical etching and the control group (P<.05). Additionally, a statistically significant difference (about 25%) was found after thermocycling (P<.05). CONCLUSIONS: Removing the Al2O3 particles embedded into the titanium surface after airborne-particle abrasion lowers the strength of the titanium-ceramic bond (P<.05). Thermocycling also weakens the strength of the titanium-ceramic bond, regardless of the surface preparation (P<.05).

Geographical location and key sensitivity issues of post-industrial regions in Europe.

Primary objectives of our work were to spatially delineate post industrial areas of the EU-27 and indicate key environmental, social and economic sensitivity issues for these regions. The density of industrial sites within NUTS-x regions for EU-27 countries was assessed by using CORINE 2000 land cover layer. A development of postindustrial society in Europe represents a strong geographic diversity. There are distinct historical and current differences between regions which form major groups, comprising similar internal characteristics and definable trends in environmental and socioeconomic sense. Regions grouped into postindustrial clusters are fundamentally different from the European average, and are facing specific problems related to global market and political changes. Eastern postindustrial regions can be characterized as socially and economically weak, exhibiting high unemployment rate, low GDP, negative population growth and a strong environmental pressure, represented by a high density of dump sites. Most of the western EU postindustrial areas have been successfully recovered and moved into new economy as shown by most of the indicators. In urban postindustrial zones, however, emission sources of pollutants seem to continually be a major problem--not necessarily in terms of exceeding thresholds, but through a remarkable difference in the amount of pollutants produced relative to other regions.

Psychosomatic aspects of arterial hypertension in women.

Arterial hypertension is one of the most widespread diseases in the world, both in women and men. In Poland, about 45% of the adult population suffers from arterial hypertension--it afflicts 45% of men and 36-38% of women. Arterial hypertension is a set of regulatory disorders of a complicated, multifactor etiology encompassing genetic conditions, the influence of the environment and some individual factors. Being also psychosomatic disorder it is strongly linked with improper adaptation to stress, personality traits and behavioural conditions esspecially with the type A behaviour pattern. This type of behaviour includes a strong need of achievement a tendency to dominate, and aggressiveness. The type A women--impatient, aggressive, hostile to their environment, committed to work and competitive--have a higher CVR (cardiovascular reactivity) coefficient and higher arterial blood pressure than type B. Some authors suggest that the lowering of estrogen levels in women over the age of 50 increases the frequency of occurrence of arterial hypertension. In spite of the fact that we do not have a full knowledge of the mechanisms starting the reaction chain, the awareness of these factors can help us decrease the risk of the development of the disease or hinder its progression.

Characteristics of depressive changes and anxiety in patients with essential hypertension.

Hypertension is among the world's most widespread diseases and one of the most frequent causes of mortality in the adult population. Clinical and experimental observations indicate the importance of psychic factors in the pathogenesis of hypertension. The aim of this study was to characterize depressive symptoms as well as to analyze anxiety level in patients with essential hypertension. A group of 38 patients, 17 females and 21 males, aged 20-77, the average age being 53, treated for essential hypertension diagnosed on the basis of the generally established clinical criteria were examined with the use of A.S. Zigmond's and R.P. Snaith's Hospital Anxiety and Depression Scale (HADS) and C.D. Spielberger's, R.L. Gorsuch's and R.E. Lushene's State-Trait Anxiety Inventory (STAI) in an authorized translation by J. Strelau, M. Tyskarczyk and K. Wrzesniewski. Examination results received with the use of HADS reveal a moderate occurrence of depressive symptoms in patients with essential hypertension. The application of STAI enabled state and trait anxiety analysis. The examined patients are characterized by an increased level of A-State as well as an increased level of A-Trait. Patients with hypertension exhibit state anxiety in reaction to all kinds of direct threat factors. They also react with an increased level of trait anxiety as an acquired behavioral disposition. This leads to a conclusion that the examined patients' reaction is marked by the anxiety disproportionate in strength to the actual danger.

Cardiac arrest and its influence on the patient's psyche.

Cardiac arrest is a very important problem, because of its aetiology and consequences. It is defined as a sudden cessation of the pumping action of the heart, leading to death, which can be prevented if proper measures are taken immediately. A very important issue is the quality of life of patients after cardiac arrest and the presence of neurological and mental disorders. The aim of this study is review of the literature relative to this subject.

A brief study about the dignity of man.

The present paper is devoted to the problem of human dignity, exploring its philosophical, psychological and religious aspects. This issue is so important in all spheres of everyday life and yet we often forget about it when we deal with our mundane problems. The paper also analyzes human dignity with regard to medicine, especially the doctor-patient relationship. It encourages a respectful attitude toward the patient as a human being.