ABSTRACT
BACKGROUND: The classification of mental, behavioural and neurodevelopmental disorders in the World Health Organization's International Classification of Diseases 11th revision (ICD-11) includes a comprehensive set of behavioural indicators (BIs) within the neurodevelopmental disorders grouping. BIs can be used to assess the severity of disorders of intellectual development in situations in which standardised measures of intellectual functioning and adaptive behaviours are not available or feasible. This international study examines the implementation characteristics of the BIs and compares them to standardised measures for assessing the severity of intellectual impairment and adaptive behaviours in disorders of intellectual development and autism spectrum disorder (ASD). The clinical utility of the ICD-11 and the fidelity of its application in international clinical settings were also assessed. METHODS: A total of 116 children and adolescents (5-18 years old) with a suspected or established diagnosis of disorders of intellectual development were included across four sites [Italy (n = 18), Sri Lanka (n = 19) and two sites in India (n = 79)]. A principal component analysis was conducted to evaluate the application of the ICD-11 guidance for combining severity levels. RESULTS: Assessment using the BIs showed a higher proportion of individuals classified with mild severity, whereas the standardised measures indicated a higher proportion of severe ratings. Additionally, individuals with co-occurring ASD tended to have more severe impairments compared with those without ASD, as indicated by both BIs and standardised measures. Overall, the BIs were considered clinically useful, although more time and consideration were required when applying the guidelines for individuals with a co-occurring disorder of intellectual development and ASD. The principal component analysis revealed one principal component representing overall disorders of intellectual development severity levels. CONCLUSIONS: The ICD-11 BIs can be implemented as intended in international clinical settings for a broad range of presentations of individuals with neurodevelopmental disorders. Use of the BIs results in similar severity diagnoses to those made using standardised measures. The BIs are expected to improve the reliability of severity assessments in settings where appropriate standardised measures for intellectual and adaptive behaviours are not available or feasible.
ABSTRACT
BACKGROUND: The World Health Organization (WHO) has approved the 11th Revision of the International Classification of Diseases (ICD-11). A version of the ICD-11 for Mental, Behavioural and Neurodevelopmental Disorders for use in clinical settings, called the Clinical Descriptions and Diagnostic Requirements (CDDR), has also been developed. The CDDR includes behavioural indicators (BIs) for assessing the severity of disorders of intellectual development (DID) as part of the section on neurodevelopmental disorders. Reliable and valid diagnostic assessment measures are needed to improve identification and treatment of individuals with DID. Although appropriately normed, standardised intellectual and adaptive behaviour assessments are considered the optimal assessment approach in this area, they are unavailable in many parts of the world. This field study tested the BIs internationally to assess the inter-rater reliability, concurrent validity, and clinical utility of the BIs for the assessment of DID. METHODS: This international study recruited a total of 206 children and adolescents (5-18 years old) with a suspected or established diagnosis of DID from four sites across three countries [Sri-Lanka (n = 57), Italy (n = 60) and two sites in India (n = 89)]. Two clinicians assessed each participant using the BIs with one conducting the clinical interview and the other observing. Diagnostic formulations using the BIs and clinical utility ratings were collected and entered independently after each assessment. At a follow-up appointment, standardised measures (Leiter-3, Vineland Adaptive Behaviour Scales-II) were used to assess intellectual and adaptive abilities. RESULTS: The BIs had excellent inter-rater reliability (intra-class correlations ranging from 0.91 to 0.97) and good to excellent concurrent validity (intra-class correlations ranging from 0.66 to 0.82) across sites. Compared to standardised measures, the BIs had more diagnostic overlap between intellectual and adaptive functioning. The BIs were rated as quick and easy to use and applicable across severities; clear and understandable with adequate to too much level of detail and specificity to describe DID; and useful for treatment selection, prognosis assessments, communication with other health care professionals, and education efforts. CONCLUSION: The inclusion of newly developed BIs within the CDDR for ICD-11 Neurodevelopmental Disorders must be supported by information on their reliability, validity, and clinical utility prior to their widespread adoption for international use. BIs were found to have excellent inter-rater reliability, good to excellent concurrent validity, and good clinical utility. This supports use of the BIs within the ICD-11 CDDR to assist with the accurate identification of individuals with DID, particularly in settings where specialised services are unavailable.
Subject(s)
International Classification of Diseases , Neurodevelopmental Disorders , Adaptation, Psychological , Adolescent , Child , Child, Preschool , Humans , Italy , Reproducibility of ResultsABSTRACT
BACKGROUND: Students with intellectual disabilities (IDs) have various learning difficulties and are at risk for school failure. Large inter-individual differences are described for reading, but it is unclear how these vary as a function of grade. The aim of this study was to examine various reading fluency, accuracy and comprehension parameters in second-to-eighth-grade Italian children with either borderline intellectual functioning (BIF) or mild ID (MID). METHODS: We examined 106 children with BIF (67 M and 39 F) and 168 children with MID (107 M and 61 F). The children were in the second to eighth grade and were comparable for chronological age (7 to 14 years). They were administered a battery of tests that assessed fluency and accuracy of word, pseudo-word and text reading, as well as text comprehension. Standardised scores allowed us to compare the performance of the two groups with normative values. RESULTS: Children with ID obtained generally low scores compared with normative values. Those with MID had greater difficulty than those with BIF. Furthermore, difficulty was greater for speed than for accuracy measures and for words than for pseudo-words. Difficulty (particularly in the case of reading speed) tended to be pronounced at later grades. Marked individual differences were present independently of MID-BIF subgrouping, as well as stimulus category and reading parameter. CONCLUSIONS: As a group, children with ID showed difficulty in reading acquisition; the effect was greater for children with more severe ID, but large individual differences were observed in children with both BIF and MID. Relatively spared pseudo-word reading skills indicate efficient use of the grapheme-to-phoneme conversion routine. This processing mode may prove more ineffective at higher levels of schooling when even in regular orthographies such as Italian typically developing children rely on lexical activation.
Subject(s)
Academic Success , Intellectual Disability/physiopathology , Reading , Adolescent , Child , Female , Humans , Male , Severity of Illness IndexABSTRACT
BACKGROUND: The Wechsler Intelligence Scale for Children - Fourth Edition often produces floor effects in individuals with intellectual disability. Calculating respondents' Z or age-equivalent scores has been claimed to remedy this problem. METHOD: The present study applied these methods to the Wechsler Intelligence Scale for Children - Fourth Edition scores of 198 individuals diagnosed with intellectual disability. Confirmatory factor analysis and profile analysis were conducted using a Bayesian approach. RESULTS: The intelligence structure in intellectual disability resembled the one previously reported for typical development, suggesting configural but not metric invariance. When Z or age-equivalent scores (but not traditional scaled scores) were used, the average profile resembled the one previously reported for other neurodevelopmental disorders. CONCLUSIONS: Both methods avoided any floor effects, generating similar but not identical profiles. Despite some practical and conceptual limitations, age-equivalent scores may be easier to interpret. This was true even for a subgroup of individuals with more severe disabilities (mean IQ < 43).
Subject(s)
Intellectual Disability/diagnosis , Neuropsychological Tests/standards , Psychometrics/standards , Wechsler Scales/standards , Adolescent , Child , Female , Humans , MaleABSTRACT
The study aimed to prospectively assess incidence and risk factors for colistin-associated nephrotoxicity. This is a secondary analysis of a multicentre, randomized clinical trial, comparing efficacy and safety of colistin versus the combination of colistin plus rifampicin in severe infections due to extensively drug-resistant (XDR) Acinetobacter baumannii. The primary end point was acute kidney injury (AKI) during colistin treatment, assessed using the AKI Network Criteria, and considering death as a competing risk. A total of 166 adult patients without baseline kidney disease on renal replacement therapy were studied. All had life-threatening infections due to colistin-susceptible XDR A. baumannii. Patients received colistin intravenously at the same initial dose (2 million international units (MIU) every 8 h) with predefined dose adjustments according to the actual renal function. Serum creatinine was measured at baseline and at days 4, 7, 11, 14 and 21 (or last day of therapy when discontinued earlier). Outcomes assessed were 'time to any kidney injury' (AKI stages 1-3) and 'time to severe kidney injury' (considering only AKI stages 2-3 as events). When evaluating overall mortality, AKI occurrence was modelled as a time-dependent variable. AKI was observed in 84 patients (50.6%, stage 1 in 40.4%), with an incidence rate of 5/100 person-days (95% CI 4-6.2). Risk estimates of AKI at 7 and 14 days were 30.6% and 58.8%. Age and previous chronic kidney disease were significantly associated with any AKI in multivariable analysis. Neither 'any' nor 'severe AKI' were associated with on-treatment mortality (p 0.32 and p 0.54, respectively). AKI occurs in one-third to one-half of colistin-treated patients and is more likely in elderly patients and in patients with kidney disease. As no impact of colistin-associated AKI on mortality was found, this adverse event should not represent a reason for withholding colistin therapy, whenever indicated.
Subject(s)
Acinetobacter Infections/drug therapy , Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Anti-Bacterial Agents/adverse effects , Colistin/adverse effects , Drug Resistance, Multiple, Bacterial , Acinetobacter baumannii/drug effects , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Colistin/administration & dosage , Creatinine/blood , Dose-Response Relationship, Drug , Endpoint Determination , Female , Humans , Incidence , Male , Middle Aged , Multivariate Analysis , Prospective Studies , Rifampin/administration & dosage , Rifampin/adverse effects , Risk AssessmentABSTRACT
FA was recently classified as carcinogen of second class (category 1B). A retrospective cohort study was conducted for the evaluation of the association between exposure to FA and cancer in professionally potentially exposed in a University setting. The cohort was composed of 140 exposed to FA and 364 not exposed in the period 1999-2015. The results showed no cancers of naso-pharynx and leukemias or lymphomas both among exposed and not exposed. Moreover, the exposure to FA is not significantly associated to an increase of other types of tumors.
Subject(s)
Formaldehyde/analysis , Leukemia/epidemiology , Lymphoma/epidemiology , Nasopharyngeal Neoplasms/epidemiology , Occupational Exposure/statistics & numerical data , Universities , Adult , Carcinoma , Female , Humans , Male , Middle Aged , Nasopharyngeal Carcinoma , Retrospective Studies , Risk , StudentsABSTRACT
Nanoparticles (NPs) are widely used in many industrial applications. NP fate and behavior in seawater are a very important issue for the assessment of their environmental impact and potential toxicity. In this study, the toxic effects of two nanomaterials, silicon dioxide (SiO2) and titanium dioxide (TiO2) NPs with similar primary size (~20 nm), on marine microalgae Dunaliella tertiolecta were investigated and compared. The dispersion behavior of SiO2 and TiO2 NPs in seawater matrix was investigated together with the relative trend of the exposed algal population growth. SiO2 aggregates rapidly reached a constant size (600 nm) irrespective of the concentration while TiO2 NP aggregates grew up to 4 ± 5 µm. The dose-response curve and population growth rate alteration of marine alga D. tertiolecta were evaluated showing that the algal population was clearly affected by the presence of TiO2 NPs. These particles showed effects on 50 % of the population at 24.10 [19.38-25.43] mg L(-1) (EC50) and a no observed effect concentration (NOEC) at 7.5 mg L(-1). The 1 % effect concentration (EC1) value was nearly above the actual estimated environmental concentration in the aquatic environment. SiO2 NPs were less toxic than TiO2 for D. tertiolecta, with EC50 and NOEC values one order of magnitude higher. The overall toxic action seemed due to the contact between aggregates and cell surfaces, but while for SiO2 a direct action upon membrane integrity could be observed after the third day of exposure, TiO2 seemed to exert its toxic action in the first hours of exposure, mostly via cell entrapment and agglomeration.
Subject(s)
Microalgae/drug effects , Nanoparticles/toxicity , Silicon Dioxide/chemistry , Silicon Dioxide/toxicity , Titanium/chemistry , Titanium/toxicity , Volvocida/drug effects , Chlorophyta/drug effects , Ecotoxicology , Seawater/chemistry , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/toxicityABSTRACT
In the past decade, an increasing number of frequently positive randomised clinical trials have been completed, allowing new consideration of the present therapeutic armamentarium for advanced renal cell carcinoma. These studies were predominantly designed to compare the experimental drugs with 1 of 2 active control arms: interferon alpha-2a or sorafenib. Different from expectations, the final results of some of these studies were not in line with the predictions, and the reasons have not been fully investigated. Consequently, there is a great need for careful analysis of the studies carried out so far, chiefly the role and validity of the control arms. In this regard, the examination of patient baseline characteristics and other factors of potential interest seems fundamental for a correct analysis of the results of these trials and consequent optimal use of the available targeted agents.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Randomized Controlled Trials as Topic/methods , Humans , Interferon-alpha/administration & dosage , Niacinamide/administration & dosage , Niacinamide/analogs & derivatives , Phenylurea Compounds/administration & dosage , Polyethylene Glycols/administration & dosage , Randomized Controlled Trials as Topic/statistics & numerical data , Recombinant Proteins/administration & dosage , SorafenibABSTRACT
OBJECTIVE: The potential benefit of further chemotherapy approaches in patients with adrenocortical carcinoma (ACC) showing progressive disease after 2 chemotherapy lines is actually unknown. This study provides explorative information on the activity of metronomic chemotherapy in heavily pre-treated ACC patients. DESIGN AND METHODS: We tested the activity of cytotoxic treatments administered on a metronomic schedule in metastatic ACC patients showing disease progression after treatment with gemcitabine and capecitabine scheme. RESULTS: Eight patients out of 28 consecutively enrolled in that trial were treated with several metronomic cytotoxic regimens. Six of them showed disease progression, but 2 patients obtained a clear benefit. The first patient was treated with oral etoposide (50 mg daily) as the 6th-line therapy and obtained a partial response lasting 24 months, while the second patient obtained a partial response lasting 10 months with metronomic oral cyclophosphamide (50 mg daily) as the 5th chemotherapy line. Both patients had sex hormone secreting tumors and were bearing a rather indolent ACC. CONCLUSIONS: The administration of several chemotherapy lines in advanced ACC patients cannot be routinely recommended outside prospective clinical trials. Few patients with indolent tumors, however, may benefit from this approach. According to our experience, oral cyclophosphamide and oral etoposide may be used in this setting.
Subject(s)
Administration, Metronomic , Adrenal Cortex Neoplasms/drug therapy , Adrenocortical Carcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Adrenal Cortex Neoplasms/pathology , Adrenocortical Carcinoma/secondary , Adult , Chemotherapy, Adjuvant , Cyclophosphamide/administration & dosage , Etoposide/administration & dosage , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Salvage Therapy , Treatment OutcomeABSTRACT
PURPOSE: evaluate the psychomotor evolution of a child with Multiple acyl-CoA dehydrogenase deficiency after treatment with L-carnitine, ubiquinone and riboflavin. METHODS: an assessment of psychomotor development was performed before the start of farmacological treatment using the Assessment Scale of Mental Development Griffiths (GMDS-R, 0-2 years). The same assessment was performed after a month and after six months of treatment to evaluate the possible benefits of treatment. RESULTS: we noticed a quick and dramatic improvement in muscular tone and motor performances after pharmacological treatment. We also observed a substantial improvement in the personal/social and hearing/language areas, suggesting the presence of intellectual/cognitive improvement. The clinical improvement correlated with the biochemical response. CONCLUSION: In our patient early therapy resulted in a optimal response in psychomotor development, motor function and muscole hypotonia. Evaluation with GMDS-R, a simple, non-invasive and multidimensional tool, represents a useful instrument to monitor the clinical response to treatment.
Subject(s)
Acyl-CoA Dehydrogenase/deficiency , Amino Acid Metabolism, Inborn Errors/drug therapy , Acidosis/etiology , Acidosis/genetics , Amino Acid Metabolism, Inborn Errors/enzymology , Amino Acid Metabolism, Inborn Errors/pathology , Carnitine/therapeutic use , Child Development , Hearing/physiology , Humans , Hypoglycemia/etiology , Hypoglycemia/genetics , Infant , Language Development , Male , Muscle Hypotonia/drug therapy , Muscle Hypotonia/etiology , Muscle, Skeletal/pathology , Neuropsychological Tests , Psychomotor Performance/physiology , Riboflavin/therapeutic use , Social Behavior , Tandem Mass Spectrometry , Ubiquinone/therapeutic use , Vitamins/therapeutic useABSTRACT
BACKGROUND: Despite progress in the process of deinstitutionalisation, very little is known about the health conditions of people with intellectual disability (PWID) who live in large institutions and PWID living in small residential services, family homes or independent living within the community. Furthermore, there are no international comparison studies at European level of the health status and health risk factors of PWID living in fully staffed residential services with formal support and care compared with those living in unstaffed family homes or independent houses with no formal support. METHODS: A total of 1269 persons with ID and/or their proxy respondents were recruited and face-to-face interviewed in 14 EU countries with the P15, a multinational assessment battery for collecting data on health indicators relevant to PWID. Participants were grouped according to their living arrangements, availability of formal support and stage of deinstitutionalisation. RESULTS: Obesity and sedentary lifestyle along with a number of illnesses such as epilepsy, mental disorders, allergies or constipation were highly prevalent among PWID. A significantly higher presence of myocardial infarctions, chronic bronchitis, osteoporosis and gastric or duodenal ulcers was found among participants in countries considered to be at the early stage of deinstitutionalisation. Regardless of deinstitutionalisation stage, important deficits in variables related to such medical health promotion measures as vaccinations, cancer screenings and medical checks were found in family homes and independent living arrangements. Age, number of people living in the same home or number of places in residential services, presence of affective symptoms and obesity require further attention as they seem to be related to an increase in the number of illnesses suffered by PWID. DISCUSSION: Particular illnesses were found to be highly prevalent in PWID. There were important differences between different living arrangements depending on the level of formal support available and the stage of deinstitutionalisation. PWID are in need of tailored primary health programs that guarantee their access to quality health and health promotion and the preventative health actions of vaccination programs, systematic health checks, specific screenings and nutritional controls. Extensive national health surveys and epidemiological studies of PWID in the EC member states are urgently needed in order to reduce increased morbidity rates among this population.
Subject(s)
Deinstitutionalization/statistics & numerical data , Health Status , Housing/statistics & numerical data , Intellectual Disability/epidemiology , Persons with Mental Disabilities/statistics & numerical data , Residential Facilities/statistics & numerical data , Activities of Daily Living , Adult , Europe/epidemiology , Female , Health Personnel/statistics & numerical data , Humans , Male , Mental Disorders/epidemiology , Middle Aged , Risk Factors , Social Support , Socioeconomic Factors , Young AdultABSTRACT
We present in this article an outline of some cyclotron-based irradiation techniques that can be used to directly radiolabel industrially manufactured nanoparticles, as well as two techniques for synthesis of labelled nanoparticles using cyclotron-generated radioactive precursor materials. These radiolabelled nanoparticles are suitable for a range of different in vitro and in vivo tracing studies of relevance to the field of nanotoxicology. A basic overview is given of the relevant physics of nuclear reactions regarding both ion-beam and neutron production of radioisotopes. The various issues that determine the practicality and usefulness of the different methods are discussed, including radioisotope yield, nuclear reaction kinetics, radiation and thermal damage, and radiolabel stability. Experimental details are presented regarding several techniques applied in our laboratories, including direct light-ion activation of dry nanoparticle samples, neutron activation of nanoparticles and suspensions using an ion-beam driven activator, spark-ignition generation of nanoparticle aerosols using activated electrode materials, and radiochemical synthesis of nanoparticles using cyclotron-produced isotopes. The application of these techniques is illustrated through short descriptions of some selected results thus far achieved. It is shown that these cyclotron-based methods offer a very useful range of options for nanoparticle radiolabelling despite some experimental difficulties associated with their application. For direct nanoparticle radiolabelling, if care is taken in choosing the experimental conditions applied, useful activity levels can be achieved in a wide range of nanoparticle types, without causing substantial thermal or radiation damage to the nanoparticle structure. Nanoparticle synthesis using radioactive precursors presents a different set of issues and offers a complementary and equally valid approach when laboratory generation of the nanoparticles is acceptable for the proposed studies, and where an appropriate radiolabel can be incorporated into the nanoparticles during synthesis.
Subject(s)
Isotope Labeling/methods , Nanoparticles/chemistry , Nanoparticles/radiation effects , Radioisotopes/chemistry , Cyclotrons , Metal Nanoparticles/chemistry , Metal Nanoparticles/radiation effects , Metal Nanoparticles/toxicity , Nanoparticles/toxicity , Radioactive Tracers , ThermodynamicsABSTRACT
BACKGROUND: Health disparities between adults with intellectual disabilities (ID) and the general population have been well documented but, to date, no dedicated assessment battery for measuring health disparity has been available. This paper reports on the development and testing of a multinational assessment battery for collecting data on a range of health indicators relevant to adults with ID. METHODS: An assessment battery (the P15) was developed following piloting, and administered to samples of adults with ID, in 14 EU countries. Samples were neither random, nor representative of the countries from which they were drawn. However, within the local health administration areas selected in each country, efforts were made to ensure samples were broadly representative of the typical living circumstances, ages and ability levels of the administrative population of adults with ID. The total sample comprised 1269 adults with ID, of whom 49% were female. The mean age was 41 years (range 19 to 90). RESULTS: Overall, feasibility, internal consistency and face validity of the P15 was acceptable. CONCLUSIONS: With some refinement the P15 could be useful for collecting data on health indicators known to be particularly important for adults with ID. It is useable in a range of countries and has the potential to highlight health inequity for adults with ID at a national or local level. Larger scale epidemiological studies are needed to exploit the potential of the P15 to address health inequity in this group.
Subject(s)
Health Status Disparities , Health Surveys , Intellectual Disability/epidemiology , Intellectual Disability/physiopathology , Adult , Aged , Aged, 80 and over , Feasibility Studies , Female , Health Surveys/methods , Health Surveys/standards , Health Surveys/statistics & numerical data , Humans , Internationality , Male , Middle Aged , Prevalence , Reproducibility of Results , Risk Factors , Young AdultABSTRACT
BACKGROUND: Nosocomial infections (NI) are above all due to health-care workers practices, but also the contamination of the environment could lead to their rise in health-care facilities. Introduction. In the last years, the incidence of NI has increased due to a substantial rise in the number of immuno-compromised patients. These patients are often gathered in hospital areas declared at "high risk" of infection such as Hematology and Bone Marrow Transplant ward. In this study, we evaluated microbial contamination of the air in two divisions with high risk patients, focusing on the validity of the air system with correlation to the presence or not of the HEPA absolute filters. METHODS: An environmental surveillance study has been carried out in two Divisions of Haematology, in two different Hospitals. Investigations have been performed by sampling air and by analyzing bacterial and fungal growth on microbiology plates after an incubation period. RESULTS: Unit A, without HEPA filters in the ventilation systems, showed a gradual increase in the bacterial load 20 and 60 days after cleaning of the ventilation system. Mycetes and Aspergilli were not present in basal conditions, at 20 or 60 days after decontamination. Unit B, equipped with HEPA filters placed at the inlet vents, showed extremely low values of the bacterial load either in basal conditions or upon inspection 60 days after cleaning. No mycetes were present. DISCUSSION: From the results obtained, it was evident that following the cleaning operation, the quality of the air is excellent in both types of equipment, since no mycetes were present and the bacterial load was < 20 CFU/mc in all the sites tested. However, although in subsequent controls mycetes were absent in both types of equipment, a great difference in the suspended bacterial load was found: Unit B was close to sterility whereas in Unit A a progressive increase was observed.
Subject(s)
Air Microbiology , Air Pollution, Indoor/analysis , Equipment Contamination , Filtration/instrumentation , Hematology , Ventilation , Air Pollution, Indoor/prevention & control , Colony Count, Microbial , Cross Infection/epidemiology , Cross Infection/microbiology , Cross Infection/prevention & control , Environmental Monitoring/methods , Epidemiological Monitoring , Hospital Design and Construction , Hospital Units , Humans , Immunocompromised Host , Incidence , Infection Control/methods , Italy/epidemiology , Lung Diseases, Fungal/epidemiology , Lung Diseases, Fungal/prevention & control , Ventilation/instrumentation , Ventilation/standardsABSTRACT
Rotavirus is acknowledged to be a major cause of acute gastroenteritis in infants and young children. As gastroenteritis due to rotavirus is a public health problem and two new vaccines are currently available, we investigated the rotavirus burden and developed a cost-effectiveness analysis, using data collected in the Province of Genoa (Italy), to evaluate the benefits of new borns vaccination. The cost-effectiveness of a rotavirus vaccination programme in the Province of Genoa was performed, in comparison with no vaccination, for both the regional healthcare system (RHS) and society (S). In 2006, admissions to the paediatric emergency department for gastroenteritis numbered 2338 (about 11% of total admissions); of these 33% were hospitalised. In 28% of cases, the children tested positive for rotavirus. During epidemics, paediatricians receive from 3 to 5 calls per day for gastroenteritis, carry out 1 or 2 ambulatory examinations and for children with a severe case history, make house visits. A rotavirus immunisation programme would have a great impact on disease burden, in that 90% coverage would reduce the number of severe cases by more than 85%. From the perspective of both the RHS and S, vaccination proved to be highly cost-effective.
Subject(s)
Cost of Illness , Immunization Programs , Rotavirus Infections/economics , Adolescent , Adult , Child , Child, Preschool , Cost-Benefit Analysis , Humans , Infant , Infant, Newborn , Middle Aged , Models, Economic , VaccinationABSTRACT
This study was conducted to assess the tolerability and efficacy of a ternary bimonthly irinotecan (CPT-11) - oxaliplatin (OHP) - infusional 5-fluorouracil (5-FU)/folinic acid (FA) combination in advanced colorectal cancer patients who had received prior CPT-11 and/or OHP-based chemotherapy regimen. Colorectal cancer patients were given bimonthly CPT-11 as a 90-min infusion, followed by OHP (85 mg/m(2)), FA (200 mg/m(2)) 2-h infusions and 5-FU (48-h infusion). CPT-11 and 5-FU doses were escalated as reported below. 26 patients were recruited. Fourteen patients had received a prior CPT-11-, 6 patients a prior OHP-based chemotherapy regimen and 6 patients both regimens. Three dose levels were investigated: CPT-11 100, 120 and 140 mg/m(2) and 5-FU 1500, 1800 and 2100 mg/m(2) in 6, 12 and 8 patients, respectively. All patients were evaluable for toxicity, 24 for antitumor activity. At all dose levels toxicity was acceptable. Grade 4 toxicity occurred in two patients only (neutropenia in one case and stomatitis in another one, 3.8%). Grade 3 toxicities included nausea and vomiting (34.6%), asthenia (26.9%), neurosensory toxicity (15.4%), neutropenia (3.8%) and diarrhea (3.8%). Hematological toxicity was infrequent and generally mild. At the third dose level, a higher, although not significantly different incidence of hematological and neurosensory toxicity (both occurring in 62.5% of cases, all grades) was observed compared to the other two, while nausea and vomiting were significantly less frequent (37.5% vs 100%). Overall, we observed 2 complete responses, 9 partial responses (OR 45.8%), 8 stable disease (33.3%), and 5 disease progression (20.8%). Median overall survival was 18 months and median time-to-progression 5.5 months. This combination showed moderate toxicity and promising antitumor activity in CPT-11 and/or OHP pretreated colorectal cancer patients. The second dose level using CPT-11 at 120 mg/m(2) and 5-FU at 1800 mg/m(2) is recommended for further phase II studies in this patient population.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Colorectal Neoplasms/drug therapy , Drug Resistance, Neoplasm/drug effects , Salvage Therapy/methods , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Irinotecan , Kaplan-Meier Estimate , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , OxaliplatinABSTRACT
The aim of this work was to investigate the mixture toxicity of Irgarol (2-methylthio-4-t-butylamino-6-cyclopropylamino-s-triazine), Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea), and copper upon the sea urchin Paracentrotus lividus and to compare the observed data with the predictions derived from approaches of Concentration Addition (CA) and Independent Action (IA). Copper spermiotoxicity was more sensitive (EC50 = 0.018 mg/L) than embryotoxicity (EC50 = 0.046 mg/L). The offspring malformations were mainly P1 type (skeletal alterations) in both cases, probably because copper competes to fix Ca2+. Irgarol and Diuron toxicity has been previously investigated. EC50 mixture embryotoxicity showed an EC50 of 1.79 mg/L, whereas spermiotoxicity mixture effects were lower than 11%. Both CA and IA modeling approaches failed to predict accurately mixture toxicity. For embryotoxicity, the IA model overestimated the mixture toxicity at effect levels of <80%. CA does not represent the worst-case approach showing values lower than IA (embryotoxicity) or similar (spermiotoxicity).
Subject(s)
Copper/toxicity , Diuron/toxicity , Herbicides/toxicity , Paracentrotus/drug effects , Triazines/toxicity , Water Pollutants, Chemical/toxicity , Animals , Embryo, Nonmammalian/drug effects , Embryonic Development/drug effects , Female , Fertilization/drug effects , Male , No-Observed-Adverse-Effect Level , Paracentrotus/physiology , Spermatozoa/drug effectsABSTRACT
Cancer often remains an incurable disease, despite significant progresses in diagnosis and treatment that have been made. Specifically, the use of nuclear medicine in oncology is greatly contributing to both imaging and therapy aspects. Targeted therapies are a major field of interest since it increases efficiency and reduces side effects. Brachytherapy is among the most valuable of recent developments for treating localized tumours resulting in improvements in improved quality of life. This is primarily because it irradiates cancerous cells most exclusively while barely effecting healthy tissue. The use of radiochemicals implies specific management for production, transport and handling that have limited the development of this technique. This review article describes brachytherapy and their latest developments. Furthermore, alternative activation methods for the production of radioisotopes and a novel delivery system for targeted multi-therapy by using PLA-ferrite nanospheres are described.