Quality of life among chronic myeloid leukemia patients in the second-line treatment with nilotinib and influential factors.

PURPOSE: This study aims to evaluate the quality of life (QoL) of chronic myeloid leukemia (CML) patients prescribed with nilotinib as a second-line therapy and explores the influential factors. METHODS: A multicenter retrospective survey was conducted via face-to-face interviews based on the EORTC QLQ-C30 questionnaire. A total of 121 adult CML patients resistant to imatinib and used nilotinib for at least 3 months were enrolled. The influential features were assessed by multiple linear regression models. RESULTS: Patients had the mean age of 47.49 (SD = 13.67) years, dominated by middle-aged and male groups. The mean scores of functions ranged from 75 to 83, and those of symptoms were from 5 to 28, with the highest of fatigue (28.28), insomnia (22.87), and pain (21.07). The mean global health status/QoL score was 67.70 (SD = 16.80) with considerable financial difficulties (52.34 (SD = 32.15)). Male patients reported higher functional scores and fewer symptoms compared with female patients. All aspects of QoL became worse with increasing age. Besides age and gender, level of education, duration of nilotinib usage, and comorbidities were also significantly influential factors in many QoL domains. A predicted model for expected mean scores of QoL domains was built based on these factors. CONCLUSIONS: The CML patients treated with nilotinib had the above-moderate QoL scores, a light decrease of functional scores, great financial difficulties, and still experienced symptoms. Strategies and more therapeutic considerations to enhance QoL for CML patients targeted toward women, the old, low educational level, and long duration of nilotinib usage, and many comorbidities are needed in the setting.

A Clinical Evidence of a Correlation Between Insulin Resistance and the ALCAT Food Intolerance Test.

Insulin resistance (IR) is defined as the inability of a known quantity of exogenous or endogenous insulin to increase glucose uptake and utilization. Several mechanisms have been proposed as possible causes underlying the development of IR and the IR syndrome. IR occurs as part of a cluster of cardiovascular-metabolic abnormalities commonly referred to as "The Metabolic Syndrome." This may lead to the development of type 2 diabetes, accelerated atherosclerosis, hypertension, dysmenorrhea, hirsutism, and polycystic ovarian syndrome, depending on the genetic background of the individual developing IR. The aim of this study was to assess, in 123 female and 35 male (mean age, 42 y ± 10.3; range 19-75 y) volunteers) whether IR could be partly related to a dietary sugar intolerance and whether there could be a correlation between the ALCAT intolerance test and a mutation of the TCFTL2 gene (it promotes the trascription of the proglucagone and plays a key role in the development of the Langherans islands). Results evidenced that subjects with an intolerance to sugar, also showed a statistically significant complete or incomplete alteration of the TCFTL2 genetic test. Based upon these findings, our study demonstrated that there is a clinical correlation between the ALCAT food intolerance test and the IR. The positivity to the ALCAT test of one of the sugars tested (fructose, sugar cane, and sugar beet) indicates, in the majority of the subjects, the presence of a mutation of the gene TCF7L2 and could contribute to the prevention and treatment of the IR.

Linkage Isomerism in Silver Acylpyrazolonato Complexes and Correlation with Their Antibacterial Activity.

Novel silver(I) acylpyrazolonato coordination polymers of formula [Ag(Q(R))]n (1-3) have been synthesized by interaction of silver nitrate with HQ(R) in methanol in the presence of an equivalent quantity of KOH (in general HQ(R) = 1-phenyl-3-methyl-4-RC(═O)-5-pyrazolone, in detail HQ(fb), R = -CF2CF2CF3; HQ(cy), R = -cyclo-C6H11; HQ(be), R = -C(H)═C(CH3)2). [Ag(Q(R))]n react with 2-ethylimidazole (2EtimH), 1-methylimidazole (Meim), and triphenylphosphine (PPh3), affording the mononuclear Ag(Q(fb))(EtimH) (4), Ag(Q(cy))(Meim)2 (5), Ag(Q(be))(Meim) (6), and Ag(Q(R))(PPh3)2 (7-9). All complexes have been analytically and spectroscopically characterized, and for some of them the X-ray crystal structure has been resolved. In particular, the single crystal molecular structure determination of Ag(Q(fb))(EtimH) and Ag(Q(be))(PPh3)2 has confirmed the different coordination modes of the HQ(fb) and HQ(be) acylpyrazolone ligands, the former being bound to the silver(I) ion in a monodentate fashion while the latter in the O2-chelating mode. Density functional theory computations suggest new insights about metal-ligand interactions and the observed linkage isomerism. While phosphine-containing complexes Ag(Q(R))(PPh3)2 (7-9) seem not to be able to efficiently inhibit the growth of Escherichia coli and Staphylococcus aureus, the polynuclear complexes [Ag(Q(R))]n (1-3) and the mononuclear Ag(Q(fb))(EtimH) (4), Ag(Q(cy))(Meim)2 (5), and Ag(Q(be))(Meim) (6) show a high and almost steady in time antibacterial activity, comparable to that of AgNO3. This activity is likely related to the degree of saturation of the silver center and to the presence of different ancillary ligands in the diverse typologies of complexes.

Novel composite plastics containing silver(I) acylpyrazolonato additives display potent antimicrobial activity by contact.

New silver(I) acylpyrazolonato derivatives displaying a mononuclear, polynuclear, or ionic nature, as a function of the ancillary azole ligands used in the synthesis, have been fully characterized by thermal analysis, solution NMR spectroscopy, solid-state IR and NMR spectroscopies, and X-ray diffraction techniques. These derivatives have been embedded in polyethylene (PE) matrix, and the antimicrobial activity of the composite materials has been tested against three bacterial strains (E. coli, P. aeruginosa, and S. aureus): Most of the composites show antimicrobial action comparable to PE embedded with AgNO3 . Tests by contact and release tests for specific migration of silver from PE composites clearly indicate that, at least in the case of the PE, for composites containing polynuclear silver(I) additives, the antimicrobial action is exerted by contact, without release of silver ions. Moreover, PE composites can be re-used several times, displaying the same antimicrobial activity. Membrane permeabilization studies and induced reactive oxygen species (ROS) generation tests confirm the disorganization of bacterial cell membranes. The cytotoxic effect, evaluated in CD34(+) cells by MTT (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazoliumbromide) and CFU (colony forming units) assays, indicates that the PE composites do not induce cytotoxicity in human cells. Studies of ecotoxicity, based on the test of Daphnia magna, confirm tolerability of the PE composites by higher organisms and exclude the release of Ag(+) ions in sufficient amounts to affect water environment.

Anionic polysaccharides for stabilization and sustained release of antimicrobial peptides.

Chemical and enzymatic in vivo degradation of antimicrobial peptides represents a major challenge for their therapeutic use to treat bacterial infections. In this work, anionic polysaccharides were investigated for their ability to increase the chemical stability and achieve sustained release of such peptides. The investigated formulations comprised a combination of antimicrobial peptides (vancomycin (VAN) and daptomycin (DAP)) and anionic polysaccharides (xanthan gum (XA), hyaluronic acid (HA), propylene glycol alginate (PGA) and alginic acid (ALG)). VAN dissolved in buffer of pH 7.4 and incubated at 37 °C showed first order degradation kinetics with a reaction rate constant kobs of 5.5 × 10-2 day-1 corresponding with a half-life of 13.9 days. However, once VAN was present in a XA, HA or PGA-based hydrogel, kobs decreased to (2.1-2.3) × 10-2 day-1 while kobs was not affected in an alginate hydrogel and a dextran solution (5.4 × 10-2 and 4.4 × 10-2 day-1). Under the same conditions, XA and PGA also effectively decreased kobs for DAP (5.6 × 10-2 day-1), whereas ALG had no effect and HA even increased the degradation rate. These results demonstrate that the investigated polysaccharides (except ALG for both peptides and HA for DAP) slowed down the degradation of VAN and DAP. DSC analysis was used to investigate on polysaccharide ability to bind water molecules. Rheological analysis highlighted that the polysaccharides containing VAN displayed an increase in G' of their formulations, pointing that the peptides interaction act as crosslinker of the polymer chains. The obtained results suggest that the mechanism of stabilization of VAN and DAP against hydrolytic degradation is conferred by electrostatic interactions between the ionizable amine groups of the drugs and the anionic carboxylate groups of the polysaccharides. This, in turn, results in a close proximity of the drugs to the polysaccharide chain, where the water molecules have a lower mobility and, therefore, a lower thermodynamic activity.

Antibacterial action of 4,4'-bipyrazolyl-based silver(I) coordination polymers embedded in PE disks.

Coupling the rigid spacer 4,4'-bipyrazole (H(2)BPZ), in its anionic or neutral form, to different silver(I) salts allowed isolation of the novel coordination polymers [Ag(2)(BPZ)] (1) and [Ag(H(2)BPZ)(X)] (X = NO(3), 2; ClO(4), 3; BF(4), 4; PF(6), 5; CH(3)SO(3), 6; CF(3)SO(3), 7), which were fully characterized by infrared and emission spectroscopies, thermal analysis, and X-ray powder diffraction. The crystal structure of 1 consists of 2-D layers containing 1-D chains of Ag(I) ions bridged by exo-tetradentate bipyrazolato moieties. The crystal structures of the [Ag(H(2)BPZ)(X)] species 2-7 feature 1-D chains of [Ag(H(2)BPZ)] stoichiometry, along which the metal centers are bridged by exo-bidentate bipyrazolyl spacers. Contacts among adjacent chains are mediated by the counterions through nonbonding interactions involving the Ag(I) ions and the pyrazolyl N-H groups. Thermogravimetric analyses disclosed the good thermal stability of these materials, decomposing in the range 200-300 °C. Under UV irradiation at room temperature, all the species showed a yellow-green emission centered in the range 520-522 nm. When embedded into polyethylene disks, 1, 2, and 4-7 demonstrated their activity as topical antibacterial agents against suspensions of E. coli, P. aeruginosa, and S. aureus: complete reduction of the three bacterial strains was achieved in 24 h, reduction of S. aureus reaching ca. 90% in only 2 h. Biocidal action was expressed also by contact susceptibility tests.

Use of an Online Platform to Evaluate the Impact of Social Distancing Measures on Psycho-Physical Well-Being in the COVID-19 Era.

Background: The SARS-CoV-2 pandemic (Severe Acute Respiratory Syndrome Coronavirus 2) and the worldwide health crisis have significantly changed both people's habits and lifestyles. Most of the studies found in the literature were carried out on specific professional categories in the socio-health sector, taking into consideration psychological disorders in relation to work. The purpose of this study was to analyze the psychological impact on a portion of the normal population subjected to lockdown. Methods: A questionnaire was distributed in the period between 23 March 2020 and 18 May 2020 (during Italian lockdown) using an online platform. The scales GAD-7, IES-r, PHQ-9 and MANSA were used to investigate the level of anxiety, the presence of post-traumatic stress disorder, the severity of depression and the perceived quality of life, respectively. Results: Four hundred and eight Italian subjects responded. Females and younger people were more affected by anxiety and depression. Post-traumatic stress disorder affected about 40% of the population sample, significantly young people and women, thus attesting to an important psychopathological response. About one-fifth of the sample population recorded an unsatisfactory quality of life. Conclusions: The results highlight the need to set up preventive interventions (primary and secondary), trying to focus on the most fragile group of subjects from a psychosocial point of view, in order to obtain a significant reduction in psychophysical damage in terms of relapses and outcomes.

Role of hydrazone substituents in determining the nuclearity and antibacterial activity of Zn(II) complexes with pyrazolone-based hydrazones.

Hydrazones and their metal derivatives are very important compounds in medicinal chemistry due to their reported variety of biological activities, such as antibacterial, antifungal and anticancer action. Five hydrazone-pyrazolone ligands H2Ln (n = 1-5) were prepared and fully characterized and their tautomerism was investigated in the solid state and solution. Five zinc(II) complexes 1-5 of composition [Zn(HLn)2] (n = 1 and 2), [Zn(HLn)2(H2O)2] (n = 3 and 5) and [Zn(HL4)2]n were synthesized and characterized by elemental analysis, IR, 1H, 19F, 13C, and 15N NMR spectroscopy, and ESI mass spectrometry. In addition, the structures of two ligands and three complexes were determined by single-crystal X-ray diffraction. The ligands H2L2 and H2L4 exist both in the NH,NH tautomeric form. Complexes 1 and 2 are mononuclear compounds, while complex 4 is a one-dimensional coordination compound. Density functional theory (DFT) calculations were carried out on proligands, their anions and all zinc complexes, confirming the experimental results, supporting IR and NMR assignments and giving proofs of the mononuclear diaqua structure of complexes 3 and 5. The antibacterial activity of the free ligands and the Zn(II) complexes was established against Escherichia coli and Staphylococcus aureus, and a strong efficiency has been found for Zn(II) complexes, particularly for the polynuclear 4 and the mononuclear diaqua complex 5, the latter containing a ligand with aliphatic and fluorinated substituents able to compromise the permeability of and disrupt the bacterial cell membrane.

Effect of a probiotic intake on oxidant and antioxidant parameters in plasma of athletes during intense exercise training.

The aim of this study was to evaluate the effect of Lactobacillus rhamnosus IMC 501 and Lactobacillus paracasei IMC 502 on oxidative stress in athletes during a four-week period of intense physical activity. Two groups of twelve subjects each were selected for this analysis. The first group consumed a daily dose of a mixture of the two probiotic strains (1:1 L. rhamnosus IMC 501 and L. paracasei IMC 502; ~10(9) cells/day) for 4 weeks. The second group (control) did not consume any supplements during the 4 weeks. Blood samples collected immediately before and after the supplementation were analyzed, and plasma levels of reactive oxygen metabolites and biological antioxidant potential were determined. Faeces were also collected and analyzed before and at the end of the probiotic supplementation. Antioxidative activity and oxidative stress resistance of the two strains were determined in vitro. Results demonstrated that intense physical activity induced oxidative stress and that probiotic supplementation increased plasma antioxidant levels, thus neutralizing reactive oxygen species. The two strains, L. rhamnosus IMC 501(®) and L. paracasei IMC 502(®), exert strong antioxidant activity. Athletes and all those exposed to oxidative stress may benefit from the ability of these probiotics to increase antioxidant levels and neutralize the effects of reactive oxygen species.

Diaphragmatic breathing reduces exercise-induced oxidative stress.

Diaphragmatic breathing is relaxing and therapeutic, reduces stress, and is a fundamental procedure of Pranayama Yoga, Zen, transcendental meditation and other meditation practices. Analysis of oxidative stress levels in people who meditate indicated that meditation correlates with lower oxidative stress levels, lower cortisol levels and higher melatonin levels. It is known that cortisol inhibits enzymes responsible for the antioxidant activity of cells and that melatonin is a strong antioxidant; therefore, in this study, we investigated the effects of diaphragmatic breathing on exercise-induced oxidative stress and the putative role of cortisol and melatonin hormones in this stress pathway. We monitored 16 athletes during an exhaustive training session. After the exercise, athletes were divided in two equivalent groups of eight subjects. Subjects of the studied group spent 1 h relaxing performing diaphragmatic breathing and concentrating on their breath in a quiet place. The other eight subjects, representing the control group, spent the same time sitting in an equivalent quite place. Results demonstrate that relaxation induced by diaphragmatic breathing increases the antioxidant defense status in athletes after exhaustive exercise. These effects correlate with the concomitant decrease in cortisol and the increase in melatonin. The consequence is a lower level of oxidative stress, which suggests that an appropriate diaphragmatic breathing could protect athletes from long-term adverse effects of free radicals.

HPV Type-Specific Prevalence a Decade after the Implementation of the Vaccination Program: Results from a Pilot Study.

Human papillomavirus infection is a cause of the development of invasive cervical cancer. Three types of vaccine are currently available to prevent precancerous/cancerous lesions due to persistent infection, which is supported mainly by 7 different high-risk genotypes. The aim of this pilot study was to acquire preliminary data on type-specific prevalence 10 years after the implementation of the HPV vaccination program in Italy, in order to subsequently plan appropriate observational studies in the Italian population. First-voided urine samples were collected from 393 consenting subjects, both females and males, aged 18-40 years, and HPV DNA was detected by PCR amplification of a 450 bp L1 fragment. All amplified products were genotyped by means of the Restriction Fragment Length Polymorphism (RFLP) method. The female population was divided into three cohorts ("vaccine-eligible", "pre-screening" and "screening" cohorts) according to the preventive intervention scheduled by age; males were included in the same three cohorts according to their year of birth. The overall prevalence of HPV infection was 19%, being higher in females than in males (22.1% vs. 13.6%, p = 0.03729). In the female population, 10 years after the start of the national immunization program, we observed a reduction in the prevalence of vaccine types and the number of circulating genotypes, especially in the "vaccine-eligible" cohort. The frequency of HPV vaccine types increased with age, particularly in males in the "pre-screening" and "screening" cohorts. Our study highlights the importance of monitoring HPV infection in both genders, to validate the effect of the HPV vaccination program.

Pro-Environmental Behaviors: Determinants and Obstacles among Italian University Students.

The awareness of citizens concerning the health risks caused by environmental pollution is growing, but studies on determinants of pro-environmental behaviors have rarely examined health-related aspects. In this study, we investigated these determinants using data from a large survey among Italian university students (15 Universities: 4778 filled questionnaires). Besides the health-related aspects, represented by environmental health risk perception and functional health literacy, we considered social and demographic characteristics (gender, area of residence, sources of information, trust in institutional and non-institutional subjects, and students' capacity of positive actions, indicated as internal locus of control). The attitudes towards pro-environmental behaviors were positive for more than 70% of students and positively related with health risk perception, internal locus of control, and health literacy. The correspondence between the positive attitudes towards pro-environmental behaviors and the real adoption of such behaviors was approximately 20% for most behaviors, except for the separate collection of waste (60%). Such a discrepancy can be attributable to external obstacles (i.e., lack of time, costs, lack of support). The health-related aspects were linked to the pro-environmental attitudes, but to a lesser extent to pro-environmental behaviors, owing to the complexity of their determinants. However, they should be taken in account in planning education interventions.

Tethering (Arene)Ru(II) Acylpyrazolones Decorated with Long Aliphatic Chains to Polystyrene Surfaces Provides Potent Antibacterial Plastics.

The acylpyrazolone proligands HQR (HQR in general, in detail: HQCy = 1-phenyl-3-methyl-4-carbonylcyclohexyl-5-pyrazolone, 4-C(O)-phenyl, HQPh = 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone, HQC17 = 1-phenyl-3-methyl-4-stearoyl-5-pyrazolone, HQC17,Ph = 1-phenyl-3-stearyl-4-benzoyl-5-pyrazolone) were synthesized and reacted with (arene)Ru(II) acceptors affording complexes [(arene)Ru(QR)Cl] (arene = cymene (cym) or hexamethylbenzene (hmb)). The complexes were characterized by elemental analyses, thermogravimetric analysis-Differntial Thermal Analysis (TGA-DTA), IR spectroscopy, ESI-MS and 1H, and 13C NMR spectroscopy. Complexes [(arene)Ru(QR)Cl] where QR = QC17 and QC17,Ph, due to the long aliphatic chain in the ligand, afford nanometric dispersions in methanol via self-assembly into micellar aggregates of dimensions 50-200 nm. The antibacterial activity of the complexes was established against Escherichia coli and Staphylococcus aureus, those containing the ligands with a long aliphatic chain being the most effective. The complexes were immobilized on polystyrene by a simple procedure, and the resulting composite materials showed to be very effective against E. coli and S. aureus.

Psychological symptoms and quality of life after repeated exposure to earthquake: A cohort study in Italy.

In 2005, a random sample of 200 people were assessed in Camerino, Italy, eight years after an earthquake. Psychological symptom levels were low and only one person had current Post-Traumatic Stress Disorder (PTSD). In 2016 a new earthquake occurred in Camerino. The study aims to assess the impact of the second exposure in the same cohort. A longitudinal study was conducted, 130 participants were re-interviewed between July and December 2017. Psychological symptoms were self-rated on the Brief Symptom Inventory (BSI) and the Global Severity Index (GSI) was analysed. Post-traumatic stress symptoms were self-rated on the Impact of Event Scale-Revised (IES-R). Subjective quality of life (SQOL) was assessed on the Manchester Short Assessment of Quality of Life (MANSA). Mean scores of GSI and IES-R were significantly higher than in 2005 (p<0.01 and p<0.001), whilst SQOL remained almost unchanged (p = 0.163). In 2017, 16.9% of the sample had reached the PTSD threshold whilst in 2005 only the 0.5% had reached it. Despite low symptom levels several years after an earthquake, people can show psychological distress after a new exposure, whilst average quality of life levels are not affected.

Food knowledge of patients at the first access to a Diabetology center. / Conoscenze alimentari in pazienti afferenti ad un centro di diabetologia

Il diabete rappresenta una patologia in costante aumento: familiarità, età e stili di vita rappresentano i principali fattori di rischio per questa malattia e per le complicanze ad essa correlate. Considerando l'importanza del regime alimentare per la prevenzione e il trattamento di questa patologia, scopo del presente studio è stato quello di valutare le conoscenze alimentari di pazienti al primo accesso presso un centro di Diabetologia e di indagare sulla loro eventuale influenza su alcuni parametri ematici. È stato somministrato il questionario di Moynihan. La relazione tra i punteggi ottenuti e le variabili emoglobina glicata, BMI, glicemia a digiuno, è stata analizzata attraverso regressione multipla basata sul metodo dei minimi quadrati ordinari (modello OLS). Il response rate è stato del 73,3%. Il punteggio medio totale ottenuto dal questionario è stato di 23,61 ed è stata osservata una correlazione statisticamente significativa (p<0,0473) tra i migliori punteggi del questionario e i valori di Hb1Ac. Questo studio è il primo passo di un'indagine più ampia che verrà condotta nell'ottica di promuovere una formazione del paziente volta a verificare nel tempo le ricadute positive sulle scelte alimentari e sui parametri clinici.

Diabetes and technology: A pilot study on the management of patients with insulin pumps during the COVID-19 pandemic.

BACKGROUND: The recent COVID-19 pandemic has accelerated the treatment process through IT/technological supports, useful in the management of chronic patients such as those affected by type 1 Diabetes Mellitus (T1DM). Specific routes for fragile patients such as those with micro-infusers have been created thanks to the application of "Diabetes Technology," which allows patients to monitor blood glucose quickly and easily. The present pilot study aimed to assess the quality of care provided to patients with micro-infusers in a delicate phase such as a pandemic lockdown. MATERIALS AND METHODS: A mixed-methods approach was used. In the first part, with prior written consent, patients with insulin pumps enrolled voluntarily. In the second part, the focus group discussion (FGD) was carried out with the voluntarily enrolled participants. The FGD data were organized and analyzed by the thematic areas. RESULTS: The number of patients with afferent insulin pumps at the center was 50 individuals. Among them, 20 patients voluntarily joined the first part of the study by completing the PACIC questionnaire, which gave an average result of 3.34 (min. 2.2 and max. 4.2). In the second part, the application of the focus group technique demonstrated that technology is decisive in the management of diabetic pathology, not only in the emergency phase. CONCLUSIONS: At the time of public health crises, alternative strategies such as Tele-Nursing or Telemedicine could be crucial for the management of patients with micro-infuser not only in critical moments, such as lockdown, but also in ordinary health management.

Immunological pattern alteration in shoe, hide, and leather industry workers exposed to hexavalent chromium.

OBJECTIVE: The aim of this work was to assess the effects of hexavalent chromium [Cr(VI)] on shoe, leather, and hide industry workers, based on the assumption that Cr(VI) can behave as an environmental immunological "stressor." METHODS: The immunological patterns of 84 male subjects were studied in relation to Cr(VI) hematic and urinary levels. Cr(VI) was measured through atomic absorption. Lymphocyte subsets, mitogen-mediated lymphocyte-proliferation, cytokine levels, and natural killer (NK) cytotoxic activity were also assayed. RESULTS: The urinary levels of the total amount of Cr(VI) were significantly higher in a subgroup of exposed subjects (group B) than in the control or in the lower exposed (group A). In group B, Cr(VI) caused a decrease in the density of glucocorticoid receptors (GR) on peripheral blood mononuclear cells (PBMC) and a increase of IL-6. Cr(VI) did not modify NK-mediated cytotoxicity, the plasmatic levels of inflammatory cytokines and related soluble receptors, and prostaglandin levels, while it tended to increase lymphocyte sensitivity to mitogens and the production of immunomodulant cytokines (IFN-gamma, IL-4, and IL-2). The experimental addition of Cr(VI) to the in vitro lymphocyte culture determined a significant inhibition of phagocytosis percentage, index, and killing percentage. These effects were neutralized by exogenous IFN-gamma. CONCLUSION: Cr(VI) could represent an environmental immunological stressor whose effects can be evaluated through laboratory surveys. The lymphocyte mitogen-induced proliferation, GR receptor on PBMC, and IL-6 plasma levels may represent a discriminating element between Cr(VI)-induced stress and other kinds of stress.

The requirements for manufacturing highly active or sensitising drugs comparing Good Manufacturing Practices.

BACKGROUND: To date there exist no internationally recognised Good Manufacturing Practices (GMP) that clearly outline universally accepted standards for manufacturing highly active or sensitising ingredients. The pharmaceutical industry is faced with a twofold problem: determining which drugs need dedicated production areas and identifying the different regulations required in different countries. The aim of this paper is to find, by comparing the current regulations of the various Regulatory Agencies, the differences between containment requirements for the production of highly active or sensitising ingredients. METHODS: An analysis of the following Regulatory Agencies' GMPs was performed: Europe (EMA), China (CFDA), Mexico (COFEPRIS), United States (FDA), Canada (Health Canada) Brazil (ANVISA), India (CDSCO), PIC/S and WHO in order to examine the differences in terms of  containment requirements set by the different Regulatory Authorities for the manufacture of highly active or sensitising ingredients. RESULTS: Our analysis found that the majority of Regulatory Agencies require that beta-lactams (sensitising materials) be produced in dedicated and segregated facilities. For "certain" highly active pharmaceutical ingredients (APIs), COFEPRIS, FDA, HC, EMA, PIC/S and WHO require that they be produced in facilities similar to those required for beta-lactams, while CDSCO, CFDA and ANVISA require that production takes place in segregated areas. Further differences between the Agencies  have emerged regarding classes of highly APIs that require dedicated production. CONCLUSION: A study of GMP adopted by Regulatory Agencies has uncovered significant differences, in particular concerning containment requirements for the production of APIs. For this reason, the harmonisation of GMP following  up-to-date quality standards based on cutting-edge science which are globally applicable is fundamental and will benefit companies and patients alike. Pharmaceutical companies would not be obliged to follow requirements enforced by the State in which they intend to manufacture a product, and patients would benefit from high-quality drugs regardless of their place of production.

A systematic review of pharmacoeconomic evaluations of erlotinib in the first-line treatment of advanced non-small cell lung cancer.

OBJECTIVE: To review and assess the quality of the available evidence on the cost-effectiveness of erlotinib in the first-line treatment of advanced non-small cell lung cancer (NSCLC). METHODS: A systematic review was conducted to identify full-text original economic evaluations of erlotinib in the first-line treatment of advanced NSCLC written in English and published from the year 2000 onwards. Study characteristics and results were recorded and compared. The quality of the studies was assessed by the Quality of Health Economic Studies (QHES) questionnaire. RESULTS: Eleven out of 130 papers were chosen for this review. Comparative regimens consisted of a best supportive care, reverse strategy, bevacizumab, cisplatin plus pemetrexed, carboplatin plus gemcitabine or gefitinib. The methods most used in these studies were modeling and sensitivity analysis and cost-effectiveness analysis. All of the studies evaluated direct costs and used quality-adjusted life-year (QALY) and life-years gained (LYG) as outcome, with 3% and 3.5% discount rate. The studies assigned ICER that ranged from dominant to I$305,510.31/QALY and from I$31,209.55/LYG to I$66,540.20/LYG. Based on the willingness to pay threshold, seven studies concluded that erlotinib was cost-effective, two studies showed that erlotinib was cost-effective on specific patients with certain conditions, and two studies comparing erlotinib with reverse strategy did not find a difference in cost-effectiveness. The high quality of these studies was confirmed using the QHES tool: the mean score was 75.77 out of 100 (SD 9.38). CONCLUSION: Most of these high-quality studies suggested that erlotinib was cost-effective in the first-line treatment of advanced NSCLC.

Evaluation of the antimicrobial activity of novel composite plastics containing two silver (I) additives, acyl pyrazolonate and acyl pyrazolone.

BACKGROUND: Public health systems today face the dual challenges of controlling infections and curbing the increase in antimicrobial resistance manifested in drug-resistant microorganisms in hospitals and elsewhere. In the last ten years, research has been conducted to develop new materials with antimicrobial properties to be used in medical devices, increasingly found to harbour critical nosocomial infections. METHODS: Two next-generation composites using the antimicrobial qualities of silver were tested against Escherichia coli, Staphylococcus aureus and Candida albicans with the purpose of evaluating their antimicrobial and antifungal activity. These tests applied the standardized method according to ISO-2216: Plastics-Measurement of Antibacterial Activity on Plastics Surfaces. Testing was carried out using polyethylene (PE) enriched with AgNO3 as a positive control and PE as a negative control. RESULTS: The antimicrobial activity of the composites proved to be between medium (bacteriostatic) and very good (bactericidal). In particular, PE2 showed the highest scores against all microorganisms, with values ranging from good to very good. Instead, PE1 had lower scores, with a value of medium for Escherichia coli and slight for Candida albicans. Statistical analysis carried out with the t-test for unpaired data showed a statistically significant difference between the positive control and the other polymers (p< .0001). CONCLUSIONS: Based on our findings, we conclude that the test, conducted to ISO-2216 standards, could be extended to include fungal strains and that the new composites could be used to produce antimicrobial surfaces for medical devices, for example, intubation tubes, urinary catheters, vascular prostheses, and mechanical heart valves. This would reduce the risk of microbial contamination and biofilm formation, ensuring better health outcomes for patients treated with these devices. Further testing should be done to evaluate potential future applications of these composites and the possibility of adding fungal strains to the IS0-2216 standard.