Application of MAPO (Movement and Assistance of Hospitalized Patients) method in hospitals and nursing homes: frequency of manual patient handling-part 2.

This study examines the evolution of MAPO method for estimating the frequency of overloading tasks in healthcare workers during different shifts. The data presented were collected from 51 in-patient wards (25 hospitals and 26 nursing homes), and 917 workers: the frequency of MPH tasks is a complementary value to the MAPO exposure level, which is useful to implement a prevention plan targeted towards the reduction of overloading tasks. Based on the frequency of manual patient handling, it appears that the afternoon shift is at greatest risk, with tasks liable to cause overloading occurring within a frequency range of 70-85 per worker. The study analyzes different pieces of equipment and their relative percentages of use, concluding that, overall, they are underutilised (especially minor aids and height-adjustable beds). Practitioner summary: The organisational data collected in hospitals and nursing homes confirms the availability of patient handling aids and equipment, but also indicates that they are underutilised with respect to the frequency of overloading tasks.

Effectiveness and safety profile of tofacitinib and baricitinib in rheumatoid arthritis patients: results from a 24-month real-life prospective study in Southern-Italy.

The primary objectives of the study were to evaluate the efficacy and safety of tofacitinib and baricitinib up to 24 months of follow-up in patients with rheumatoid arthritis (RA) treated in Southern Italy. Patients' data, activity index, and clinimetric scores were collected at baseline (T0), six (T6), twelve (T12), and twenty-four (T24) months following treatment initiation. At six, twelve, and twenty-four months, adverse events and treatment cessation were also recorded. Sixty-eight patients (mean age: 62.2±10.9 years; mean RA duration: 15±9.6 years) were enrolled over a period of 12 weeks. At baseline, twenty-four patients (35.3%) were treated with tofacitinib, and forty-four patients (64.7%) were treated with baricitinib. The baseline mean disease activity was moderate as measured by DAS28- ESR (5.0±1.0), DAS 28 CRP (4.69±0.94), and SDAI (26.87±10.73) score. Before beginning JAKinhibs therapy, thirty-two patients (61.8%) were taking bDMARDs, while the remaining thirty-six (38.2%) were bDMARDs-naïve. The 24-month retention rate for JAKinhibs was 91.1%. Six months after beginning treatment with JAKinhibs, a statistically significant improvement was observed in all evaluated activity indices and clinimetric scores. Improvement was confirmed during the 12- and 24-month follow-up evaluations. The positive correlation between baseline-T6 SDAI delta and discontinuation of JAKinhibs (p=0.02) suggests that RA worsening in the first six months may be a predictor of therapy withdrawal. Patients with RA responded favorably to tofacitinib and baricitinib in this prospective, real-world study from a single center in Southern Italy. Efficacy was observed despite an underlying persistent and treatment-resistant disease.

Genetics of population exchange along the historical Portuguese-Spanish border.

The present analysis compares the distribution of surnames by means of spatial autocorrelation analysis in the Spain-Portugal border region. The Spanish National Institute of Statistics provides a database of surnames of residents in the western Spanish provinces of Zamora, Salamanca, Cáceres, Badajoz and Huelva. The Spanish and Portuguese patterns of surname distribution were established according to various geographic axes. The results obtained show a low diversity of surnames in this region - especially in the centre - which can be explained by the absence of any major geographic barriers, with the exception of the mountain ranges between hydrographic basins, and by the presence of traditional roads that have existed since Roman times. The latter have resulted in a constant migratory flow over short-median distances, which, as can be deduced from the surnames, fits two north/south territorial axes running parallel to the border between Spain and Portugal. The distribution patterns of Portuguese and Spanish surnames differ with regard to their frequencies in the five provinces studied, which can be attributed to their respective historical, economic and social conditions. It is concluded that the border delimiting these two countries has affected the migratory flow, thereby conditioning the demographic and genetic structure of the western Spanish regions.

Methotrexate consolidation treatment according to pharmacogenetics of MTHFR ameliorates event-free survival in childhood acute lymphoblastic leukaemia.

Recent advances in treatment for childhood acute lymphoblastic leukaemia (ALL) have significantly increased outcome. High-dose methotrexate (MTX) is the most commonly used regimen during the consolidation period, but the optimal dose remains to be defined. We investigated the usefulness of the MTHFR genotype to increase the MTX dosage in the consolidation phase in 141 childhood ALL patients enrolled in the ALL/SHOP-2005 protocol. We also investigated the pharmacogenetic role of polymorphisms in genes involved in MTX metabolism on therapy-related toxicity and survival. Patients with a favourable MTHFR genotype (normal enzymatic activity) treated with MTX doses of 5 g m⁻² had a significantly lower risk of suffering an event than patients with an unfavourable MTHFR genotype (reduced enzymatic activity) that were treated with the classical MTX dose of 3 g m⁻² (P=0.012). Our results indicate that analysis of the MTHFR genotype is a useful tool to optimise MTX therapy in childhood patients with ALL.

Micronutrients deficiencies in patients with spondylarthritis: the potential immunometabolic crosstalk in disease phenotype.

OBJECTIVE: Micronutrient deficiencies (MNDs) are common among patients with certain chronic inflammatory diseases. They are associated with a pro-inflammatory status and co-morbidities. However, no studies have specifically investigated MNDs in Spondyloarthritis (SpA). This paper aimed at analyzing the occurrence of anemia and deficiencies of ferritin (Fe), vitamin D [25(OH)D], vitamin B12 (B12), and folic acid (FA) in SpA patients. The interplay of MNDs with age, gender, and metabolic abnormalities was also explored. PATIENTS AND METHODS: MNDs were evaluated in 220 SpA outpatients (137 females and 83 age-matched males) with psoriatic arthritis (PsA, n=110) and non-psoriatic SpA (n=110). Metabolic parameters were analyzed. Disease activity was assessed by either Disease Activity in PSoriatic Arthritis (DAPSA) or Ankylosing Spondylitis Disease Activity Score with C-Reactive Protein (ASDAS-CRP) as appropriate, while the functional status was evaluated using Health Assessment Questionnaire modified for SpA (HAQ-S). RESULTS: Anemia occurred in 13.6% of subjects of the study cohort and almost wholly in females (p=0.004). Females showed higher Fe deficiency (p=0.04) and lower Fe levels (p=0.0003) than males. Hemoglobin (Hb) resulted inversely related to age and CRP (p=0.01 and p=0.008) in male group. The 25(OH)D deficiency (≤20 ng/ml) was present in 23.2% of the cohort with a higher prevalence in males than females (p=0.02): moreover, 25(OH)D inversely correlated with disease duration (p=0.02) in males. The B12 deficiency (≤200 pmol/l) was rare (13.2%), while FA ≤4 ng/ml was frequent (22%) and associated with B12 deficiency in 31% of cases. SpA patients in moderate/high disease activity had higher Body Mass Index (BMI) (p=0.04) and HAQ-S (p<0.0001), as well as lower Hb (p=0.02), and Fe (p=0.03) than patients in remission/low disease activity (LDA). In patients with extra-articular manifestations, female sex was prevalent (F:M=2) and B12 levels were lower than in patients without (p=0.005). Interestingly, 25(OH)D was lower (p=0.04) and both BMI and HAQ-S (p=0.036 and p=0.01) were higher in patients without extra-articular involvement than patients with. CONCLUSIONS: Our findings documented a relevant prevalence of MNDs in SpA patients, and its strict interplay with gender and metabolic abnormalities by highlighting the role of MNDs in inflammatory-dependent dysmetabolism in SpA.

Similarities in the surnames of island and continental populations of the north-western Mediterranean area.

This paper compares the structures of the surnames of 75 municipal populations living in six north-western Mediterranean regions. Its purpose is to unravel the relations between the local populations in Corsica and Sardinia and the links between these populations and those living in the Italian and French continental territory. On the basis of the matrix of similarity of surnames, some topological representations have been drafted showing the above-mentioned relations between populations under the light of their geographical position, their recent history and studies of genetic analysis. Corsica has an eterogeneous surname structure and evident similarity of the north with Tuscany and some centres of continental France. When only the populations of Sardinia were taken into consideration, it emerged that they differ among each other in relation to their geographical position and their history; when, instead, they were considered in relation to other populations outside the island, it was possible to observe that they form a highly different cluster. This study also identified many differences in the analysed geographical areas of Sardinia. In the minor islands - Elba, Giglio, Capraia - the structure of the surnames has a Tuscan origin as well as some similarity with other geographically distant areas, as in the case of the island of Giglio, if compared with some communities of Liguria.

Cyclophosphamide metabolism in children.

The alkylating agent cyclophosphamide is a prodrug which is metabolized in vivo to produce both therapeutic and toxic effects. Cyclophosphamide metabolism was investigated in 36 children with various malignancies. Concentrations of cyclophosphamide and its principal metabolites were measured in plasma and urine using a quantitative high-performance TLC method. The results indicated a high degree of inter-patient variation in metabolism. In contrast to previous adult studies on urinary metabolites, plasma carboxyphosphamide concentrations did not support the existence of polymorphic metabolism. Plasma concentrations of dechlorethylcyclophosphamide and carboxyphosphamide were correlated in individual patients, suggesting that the activity of both aldehyde dehydrogenase and cytochrome P450 enzyme(s) determine carboxyphosphamide production in vivo. The presence of ketocyclophosphamide in plasma was strongly associated with dexamethasone pretreatment and was also accompanied by a high clearance of the parent drug. Interpatient differences in metabolism reflect individual levels of enzyme expression and may contribute to variation in clinical effect.

Genetic abnormalities associated with the t(12;21) and their impact in the outcome of 56 patients with B-precursor acute lymphoblastic leukemia.

The ETV6/RUNX1 rearrangement is found in 20-30% of children with B-cell precursor acute lymphoblastic leukemia and is associated with a good outcome. To determine the cytogenetic and molecular abnormalities associated with the ETV6/RUNX1 rearrangement and the influence of this rearrangement in patients' evolution, we analyzed the molecular cytogenetic profiles of 56 children with this rearrangement and B-cell precursor acute lymphoblastic leukemia. Secondary changes detected with conventional cytogenetics and with fluorescence in situ hybridization were found in 71.4% of cases, the most frequent being the loss of the normal ETV6 allele, 12p aberrations, duplication of the fusion gene, and trisomy 21, as in replicating the results of previous studies. In this preliminary series, with a mean follow-up of 69.3 months, secondary abnormalities did not influence patients' outcome. It seems therefore that the prognostic value of the t(12;21) does not vary and that ETV6/RUNX1 rearrangement is an independent indicator of good prognosis.

Pharmacokinetics and metabolism of cyclophosphamide in paediatric patients.

The pharmacokinetics and metabolism of cyclophosphamide were studied in nine paediatric patients. Plasma samples were obtained from eight subjects and urine was collected from six children during a 24-h period after drug administration. Cyclophosphamide and its major metabolites phosphoramide mustard (PM), carboxyphosphamide (CX), dechloroethylcyclophosphamide (DCCP) and 4-ketocyclophosphamide (KETO) were determined in plasma and urine using high-performance thin-layer chromatography-photographic densitometry (HPTLC-PD). Cyclophosphamide (CP) was nearly, if not completely, cleared from plasma by 24 h after its administration. The plasma half-life of CP ranged from 2.15 to 8.15 h; it decreased following higher doses and was shorter than that previously reported for adult patients. Both the apparent volume of distribution (0.49 +/- 1.4 l/kg) and the total body clearance (2.14 +/- 1.4 l m-2 h-1) increased with increasing dose. Renal clearance ranged between 0.12 and 0.58 l/h (mean, 0.43 +/- 0.19 l/h). Between 5.4% and 86.1% of the total delivered dose was recovered as unchanged drug in the urine. The major metabolites identified in plasma and urine were PM and CX. One patient appeared to be deficient in CX formation. This study suggests that there is interpatient variability in the pharmacokinetics and metabolism of CP in paediatric patients. The shorter half-life and higher clearance as compared with adult values indicate faster CP metabolism in children.

Argyrophilic nucleolar organizer region counts and Ki-67 scores in human renal cell carcinoma.

The proliferative activity of 21 cases of renal cell carcinoma has been investigated by means of monoclonal antibody Ki-67 and Nucleolar Organizer Regions (AgNORs) analysis. The correlation between AgNOR counts and Ki-67 scores was only slightly significant (r = 0.53, r2 = 0.28) as determined by linear regression. Positive correlation was found between Ki-67 scores and tumour histologic grade. However, no correlation was observed between Ki-67 scores and tumour pathologic stage and between AgNOR counts and tumour histologic grade and/or pathologic stage. The results suggest that AgNOR counts cannot replace Ki-67 scores in evaluating the proliferative activity of renal cell carcinoma and that such activity and both histologic grade and pathologic stage seem to be independent parametres.

Neuroblastoma and bronchogenic cyst: a rare association.

A few of the known associations between paediatric cancer and congenital anomalies are attributable to contiguous-gene syndromes. Neuroblastoma (NB) has been linked with an excess of gastrointestinal malformations, but there is a significant scarcity of associated respiratory anomalies. We report on two children having an abdominal NB and a bronchogenic cyst diagnosed simultaneously and in different order of appearance. Both masses were removed in separated procedures, taking into account the priority and the time sequence of chemotherapy. Literature is reviewed, checking that the genetic basis for this association is supported by speculations about the oncogene RON.

Outdoor background ELF magnetic fields in an urban environment.

Classification of 'exposed/non-exposed' subjects in epidemiological studies concerning the possible cancer risk associated with ELF magnetic field exposure is based on the a priori assumption of magnetic field value cut-off points that, often, are defined equal to minimum exposure levels typical of a population residing near high voltage facilities (0.1-4.2 microT), but in some cases an environmental magnetic field level not associated with transmission lines can exist. The results of an ELF magnetic field survey in an Italian urban area (about 1 million inhabitants) are presented: average field levels are correlated with population density of different districts. Exposure indexes are obtained, which are compared with those evaluated in studies regarding domestic exposure: background average levels result in comparable to cut-off points in epidemiological studies, but in some districts with high population density, they are much higher. This shows that knowledge of background magnetic field level in urban areas can assume a significant role in exposure assessment.

[Prostate cancer: transrectal high-intensity focused ultrasound for the treatment of local recurrence after radical prostatectomy or radiotherapy].

OBJECTIVES. To evaluate the efficacy and safety of transrectal high-intensity focused ultrasound (HIFU) as salvage therapy for locally recurrent prostate cancer after external beam radiotherapy or recurrences located in the region of vesicourethral anastomosis after radical prostatectomy. METHODS. Transrectal biopsy of the prostate (recurrence after radiotherapy) or in the region of vesicourethral anastomosis (recurrence after prostatectomy) was performed in all cases at the time of biochemical relapse. Only patients with positive biopsy were treated. Systemic disease was excluded by PET-CT and bone scan. All treatments were carried out under spinal anesthesia. The device used was Ablatherm (EDAP, Lion, France). The patients were followed with PSA measurement every 3 months and clinical examination every 6 months. In case of biochemical relapse we performed re-biopsy. RESULTS. From 2002 to 2008 we treated 19 patients with local recurrence after radiotherapy. The mean follow-up was 30 months for each patient (range 6-72 months). 9 patients (47%) are disease-free at last followup, with PSA < 1 ng/mL. 9 patients experienced biochemical failure: 8 were treated with androgen deprivation, 1 with salvage prostatectomy. 2 patients died of the disease. Adverse events related to HIFU included 1 rectourethral fistula (observed before the use of specific parameters dedicated to this patient population) and mild incontinence (2-3 pads/die) in 4 patients. From 2002 to 2008 we treated 27 patients with a local recurrence after radical prostatectomy. Mean pre-HIFU PSA was 2.17 ng/mL (range 0.5-8 ng/ml); the Gleason score ranged from 5 to 8. All patients reached a minimum follow-up of 20 months (range 20-80 months). Median PSA nadir was 0.2 ng/ml. The disease-free rate was 51% (14/27); these patients have a median PSA of 0.2 ng/ml at last follow-up. 81% (22/27) of control biopsies were negative. There were no intra-operative or post-operative complications. CONCLUSIONS. The small number of patients in our series limits our ability to draw any definitive conclusions. We believe that HIFU may be a potentially useful treatment option for patients who develop prostate cancer recurrence after external beam radiotherapy or in the region of vesicourethral anastomosis after radical prostatectomy. The procedure is safe, side effects are acceptable and do not add significant morbidity to the previous radical treatment. HIFU lesions are targeted only to the area of recurrence. It is important to remember that, in case of failure, the patient can undertake any other therapies.

Surnames as alleles: spatial distribution of surnames in a province of the Italian Alps.

The present paper seeks to analyse the spatial distribution of surnames in the province of Belluno in the Italian Alps, and describes the internal mobility of the population taking into consideration one of the most important and ancient roads in the area. The study is based on the analysis of the similarity of the frequencies of some autochthonous surnames depending on their geographical distance apart. The population considered turned out to be basically sedentary. When forced to migrate, the population preferred to go far from their homeland rather than inside the area: this happened probably because the opportunities that the province of Belluno could offer were quite scarce throughout the whole territory, and people hoped to improve their economic situation by going abroad.

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) treated with 2-chlorodeoxyadenosine.

Sinus histiocytosis with massive lymphadenopathy (SHML) or Rosai-Dorfman disease (RDD) is a rare but well-defined histiocytic proliferative disorder of unknown etiology that usually presents with cervical lymphadenopathy, fever, leukocytosis, and hypergammaglobulinemia in an otherwise healthy child. Although many patients undergo spontaneous remission, a subset of patients with systemic disease has a more serious course. For those patients with a poor outcome, steroids and chemotherapeutic agents such as etoposide or 6-mercaptopurine plus low dose methotrexate have been used. We present a child with a massive cervical lymphadenopathy treated with 2-chlorodeoxyadenosine (2-CdA, cladribine) after other approaches failed.

Mortality of the German linguistic isolates of the western Italian Alps (Walser).

For five localities of Western Alps (Val d'Aosta and Piemonte) inhabited by Walser populations (Gressoney-la-Trinité, Gressoney St. Jean, Issime, Macugnaga and Rima) the main features of mortality are described, namely raw death rate, seasonality of deaths, distribution of deaths according to age classes and infant mortality. Death rate is higher than the Italian average value; seasonality of deaths shows some statistically significative differences only in a few decades and does not reach a high significativity. Distribution in age classes shows a rather low mortality at lower ages (0 and 1-4 years) with small changes between the two halves of the 20th century. An exception is constituted by Macugnaga, where an elevated mortality at lower age classes is present in both halves of the century, though higher in the first one. The picture can be considered as not typical of Walser populations. Infant mortality shows great variations in the investigated isolates, but an explication today is impossible. The degree of illiteracy, one of the causes of infant mortality, is rather elevated only at Macugnaga (until 1931). A comparison is made with other German linguistic islands studied so far by one of the two authors (G.M.).