Atomic layer deposition-A novel method for the ultrathin coating of minitablets

We introduce atomic layer deposition (ALD) as a novel method for the ultrathin coating (nanolayering) of minitablets. The effects of ALD coating on the tablet characteristics and taste masking were investigated and compared with the established coating method. Minitablets containing bitter tasting denatonium benzoate were coated by ALD using three different TiO2 nanolayer thicknesses (number of deposition cycles). The established coating of minitablets was performed in a laboratory-scale fluidized-bed apparatus using four concentration levels of aqueous Eudragit (R) E coating polymer. The coated minitablets were studied with respect to the surface morphology, taste masking capacity, in vitro disintegration and dissolution, mechanical properties, and uniformity of content. The ALD thin coating resulted in minimal increase in the dimensions and weight of minitablets in comparison to original tablet cores. Surprisingly, ALD coating with TiO2 nanolayers decreased the mechanical strength, and accelerated the in vitro disintegration of minitablets. Unlike previous studies, the studied levels of TiO2 nanolayers on tablets were also inadequate for effective taste masking. In summary, ALD permits a simple and rapid method for the ultrathin coating (nanolayering) of minitablets, and provides nanoscale-range TiO2 coatings on porous minitablets. More research, however, is needed to clarify its potential in tablet taste masking applications. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

Evaluation of new flavors for feline mini-tablet formulations

Despite a global interest in companion animal pharmaceuticals, feline peroral medication is still lacking in palatable and voluntarily acceptable drugs of suitable size and attractive taste. As a consequence, treating cats with canine or human medicinal products has weakened patient compliance and treatment commitment resulting in many pet cats going untreated. In the future, the companion animal pharmaceutical business is expected to focus particularly on cats and the development of palatable feline medication. Based on this, the overall aim of this study was to facilitate voluntary drug administration to felines. Specifically the aim was to develop sophisticated and tailor-made feline medicinal products, in the form of mini-tablets, focusing on flavors palatable to felines. Rapid preformulation compatibility and stability screening tests of synthetic flavors were carried out using readily available oral solid form excipients. On the basis that felines are carnivorous, Lmethionine, L-leucine, L-proline and thiamine hydrochloride were investigated as possible flavors for improving palatability. These flavors, together with a model substance for a bitter taste, denatonium benzoate, were evaluated for their physicochemical properties, stability and physical compatibility. This evaluation was carried out with the substances alone and in binary combinations of flavors and excipients. Stability and compatibility were examined using differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). The results showed that L-proline and denatonium benzoate anhydrate were hygroscopic. Thiamine hydrochloride was incompatible with talc and sodium stearyl fumarate. The known incompatibility between the amines contained in flavors, and α-lactose monohydrate was used to assess method sensitivity. Overall, this study provided new information on the compatibility of novel flavors with oral solid form excipients. This study also showed the applicability of using XRPD and DSC for the rapid evaluation of instability and incompatibility

Hyvä, paha informaatio : informaatio-oikeuden erityiskysymyksiä

fi=vertaisarvioimaton|en=nonPeerReviewed

Heart Rate Dynamics after Exercise in Cardiac Patients with and without Type 2 Diabetes

Purpose: The incidence of cardiovascular events is higher in coronary artery disease patients with type 2 diabetes (CAD + T2D) than in CAD patients without T2D. There is increasing evidence that the recovery phase after exercise is a vulnerable phase for various cardiovascular events. We hypothesized that autonomic regulation differs in CAD patients with and without T2D during post-exercise condition. Methods: A symptom-limited maximal exercise test on a bicycle ergometer was performed for 68 CAD + T2D patients (age 61 ± 5 years, 78% males, ejection fraction (EF) 67 ± 8, 100% on β-blockade), and 64 CAD patients (age 62 ± 5 years, 80% males, EF 64 ± 8, 100% on β-blockade). Heart rate (HR) recovery after exercise was calculated as the slope of HR during the first 60 s after cessation of exercise (HRRslope). R–R intervals were measured before (5 min) and after exercise from 3 to 8 min, both in a supine position. R–R intervals were analyzed using time and frequency methods and a detrended fluctuation method (α1). Results: BMI was 30 ± 4 vs. 27 ± 3 kg m2 (p < 0.001); maximal exercise capacity, 6.5 ± 1.7 vs. 7.7 ± 1.9 METs (p < 0.001); maximal HR, 128 ± 19 vs. 132 ± 18 bpm (p = ns); and HRRslope, −0.53 ± 0.17 vs. −0.62 ± 0.15 beats/s (p = 0.004), for CAD patients with and without T2D, respectively. There was no differences between the groups in HRRslope after adjustment for METs, BMI, and medication (ANCOVA, p = 0.228 for T2D and, e.g., p = 0.030 for METs). CAD + T2D patients had a higher HR at rest than non-diabetic patients (57 ± 10 vs. 54 ± 6 bpm, p = 0.030), but no other differences were observed in HR dynamics at rest or in post-exercise condition. Conclusion: HR recovery is delayed in CAD + T2D patients, suggesting impairment of vagal activity and/or augmented sympathetic activity after exercise. Blunted HR recovery after exercise in diabetic patients compared with non-diabetic patients is more closely related to low exercise capacity and obesity than to T2D itself

Perinatal and perioperative factors associated with mortality and an increased need for hospital care in infants with transposition of the great arteries : A nationwide 11-year population-based cohort

Introduction Newborn infants with transposition of the great arteries (d-TGA) need immediate care for an optimal outcome. This study comprised a nationwide 11-year population-based cohort of d-TGA infants, and assessed whether the implementation of a nationwide systematic fetal screening program, or other perinatal, or perioperative factors, are associated with mortality or an increased need for hospital care. Material and methods The national cohort consisted of all live-born infants with simple d-TGA (TGA +/- small ventricular septal defect, n = 127) born in Finland during 2004-2014. Data were collected from six national registries. Prenatal diagnosis and perinatal and perioperative factors associated with mortality and length of hospitalization were evaluated. Results Preoperative mortality was 7.9%, and the total mortality was 8.7%. The prenatal detection rate increased after introducing systematic fetal anomaly screening from 5.0% to 37.7% during the study period (P <.0001), but the total mortality rate remained unchanged. All prenatally diagnosed infants (n = 27) survived. Lower gestational age (odds ratio 0.68,P = .012) and higher maternal age at birth (odds ratio 1.16,P = .036) were associated with increased mortality in multivariable analysis. Older infant age at time of operation (P = .002), longer aortic clamp time (P <.001), and higher maternal body mass index (P = .027) were associated with longer initial hospital stay. An extended need for hospital care during the first year of life was multi-factorial. Conclusions In our cohort, none of the prenatally diagnosed d-TGA infants died. As a result of the limited prenatal detection rates, however, the sample size was insufficient to reach statistical significance. The d-TGA infants born with lower gestational age and to older mothers had increased mortality.Peer reviewe

Clinical characteristics and evaluation of the incidence of cryptococcosis in Finland 2004-2018

Background Cryptococcosis is one of the major causes of mortality among HIV patients worldwide. Though most often associated with late stage HIV infection/AIDS, a significant number of cases occur in other immunocompromised patients such as solid organ transplant recipients and patients with hematological malignancies. Immunocompromised patients are a heterogeneous group and their number increases constantly. Since little is known about the incidence and the clinical features of cryptococcosis in Northern Europe, our aim was to investigate the clinical characteristics of cryptococcosis patients in Finland. Methods We retrospectively reviewed the laboratory confirmed cryptococcosis cases in Finland during 2004-2018. Only those who were treated for cryptococcosis were included in the study. Initial laboratory findings and medical records were also collected. Results A total of 22 patients with cryptococcosis were included in our study. The annual incidence of cryptococcosis was 0.03 cases per 100,000 population. Ten patients were HIV-positive and 12 out of 22 were HIV-negative. Hematological malignancy was the most common underlying condition among HIV-negative patients. Conclusions To our knowledge, this is the first study of the clinical presentation and incidence of cryptococcosis in Finland. We demonstrate that invasive cryptococcal infection occurs not only in HIV/AIDS patients or otherwise immunocompromised patients but also in immunocompetent individuals. Even though cryptococcosis is extremely rare in Finland, its recognition is important since the prognosis depends on rapid diagnostics and early antifungal therapy.Peer reviewe

Long-term follow up of families with pathogenic NFKB1 variants reveals incomplete penetrance and frequent inflammatory sequelae

Publisher Copyright: © 2022 The AuthorsNuclear factor κ light-chain enhancer of activated B cells (NF-κB) family of evolutionarily conserved transcription factors are involved in key cellular signaling pathways. Previously, hypogammaglobulinemia and common variable immunodeficiency (CVID)-like phenotypes have been associated with NFKB1 variants and loss-of-function NFKB1 variants have been reported as the most common monogenic cause for CVID among Europeans. Here, we describe a Finnish cohort of NFKB1 carriers consisting of 31 living subjects in six different families carrying five distinct heterozygous variants. In contrast to previous reports, the clinical penetrance was not complete even with advancing age and the prevalence of CVID/hypogammaglobulinemia was significantly lower, whereas (auto)inflammatory manifestations were more common (42% of the total cohort). At current stage of knowledge, routine genetic screening of asymptomatic individuals is not recommended, but counseling of potential adult carriers seems necessary.Peer reviewe

Clinical characteristics and evaluation of the incidence of cryptococcosis in Finland 2004-2018

Background: Cryptococcosis is one of the major causes of mortality among HIV patients worldwide. Though most often associated with late stage HIV infection/AIDS, a significant number of cases occur in other immunocompromised patients such as solid organ transplant recipients and patients with hematological malignancies. Immunocompromised patients are a heterogeneous group and their number increases constantly. Since little is known about the incidence and the clinical features of cryptococcosis in Northern Europe, our aim was to investigate the clinical characteristics of cryptococcosis patients in Finland.Methods: We retrospectively reviewed the laboratory confirmed cryptococcosis cases in Finland during 2004-2018. Only those who were treated for cryptococcosis were included in the study. Initial laboratory findings and medical records were also collected.Results: A total of 22 patients with cryptococcosis were included in our study. The annual incidence of cryptococcosis was 0.03 cases per 100,000 population. Ten patients were HIV-positive and 12 out of 22 were HIV-negative. Hematological malignancy was the most common underlying condition among HIV-negative patients.Conclusions: To our knowledge, this is the first study of the clinical presentation and incidence of cryptococcosis in Finland. We demonstrate that invasive cryptococcal infection occurs not only in HIV/AIDS patients or otherwise immunocompromised patients but also in immunocompetent individuals. Even though cryptococcosis is extremely rare in Finland, its recognition is important since the prognosis depends on rapid diagnostics and early antifungal therapy.</p

A call for action: Improve reporting of research studies to increase the scientific basis for regulatory decision-making

Publisher's version (útgefin grein)This is a call for action to scientific journals to introduce reporting requirements for toxicity and ecotoxicity studies. Such reporting requirements will support the use of peer‐reviewed research studies in regulatory decision‐making. Moreover, this could improve the reliability and reproducibility of published studies in general and make better use of the resources spent in research.Nordic Council of Minister

A cluster of Candida krusei infections in a haematological unit

<p>Abstract</p> <p>Background</p> <p><it>Candida krusei </it>infections are associated with high mortality. In order to explore ways to prevent these infections, we investigated potential routes for nosocomial spread and possible clonality of <it>C. krusei </it>in a haematological unit which had experienced an unusually high incidence of cases.</p> <p>Methods</p> <p>We searched for <it>C. krusei </it>contamination of the hospital environment and determined the level of colonization in patients and health care workers. We also analyzed the possible association between exposure to prophylactic antifungals or chemotherapeutic agents and occurrence of <it>C. krusei</it>. The <it>C. krusei </it>isolates found were genotyped by pulsed-field electrophoresis method in order to determine possible relatedness of the cases.</p> <p>Results</p> <p>Twelve patients with invasive <it>C. krusei </it>infection and ten patients with potentially significant infection or mucosal colonization were documented within nine months. We were unable to identify any exogenic source of infection or colonization. Genetic analysis of the isolates showed little evidence of clonal transmission of <it>C. krusei </it>strains between the patients. Instead, each patient was colonized or infected by several different closely related genotypes. No association between medications and occurrence of <it>C. krusei </it>was found.</p> <p>Conclusion</p> <p>Little evidence of nosocomial spread of a single <it>C. krusei </it>clone was found. The outbreak may have been controlled by cessation of prophylactic antifungals and by intensifying infection control measures, e.g. hand hygiene and cohorting of the patients, although no clear association with these factors was demonstrated.</p