Occult HBV infection may negatively impact on drug survival in patients with rheumatoid arthritis on treatment with a first biologic drug. An appraisal from the Biologic Apulian Registry (BIOPURE).

We performed a retrospective analysis to evaluate the survival on first line biologic drug of rheumatoid arthritis (RA) patients with potential occult HBV infection (pOBI). We analysed longitudinal data of 486 consecutive RA patients starting a first biological drug in a time frame from 1st January 2008 to 31st December 2014. Demographic and disease related characteristics were collected at baseline and at the last observation visit. Baseline serological markers of HBV infection and causes of treatment discontinuation were also recorded. Primary endpoint was the influence of pOBI on drug survival, estimated by Kaplan-Meier life table analysis. Estimates hazard ratios (HRs) of drug discontinuation, adjusted for disease characteristics, biological drug class and HBcAb status were computed by Cox-regression models. The retention rate was significantly lower in pOBI positive patients (58.2%) when compared to pOBI negative ones (67.8%) and this data was confirmed also when only discontinuation due to ineffectiveness was considered (pOBI positive 66.4% vs pOBI negative 75.3%, long rank 7.93, p=0.005). Cox regression models showed a significant association between HBcAb-neg (HR 0.58, 0.41-0.84), higher ESR-DAS28 at baseline (HR 1.07, 1.03-1.11) or RF/ACPA-neg (HR 1.46, 1.04-2.06) and drug discontinuation. Occult HBV infection seems to influence negatively the effectiveness of biological therapies in RA patients.

Two repetitive bouts of intense eccentric-concentric jaw exercises reduce experimental muscle pain in healthy subjects.

High-intensity eccentric-concentric contractions of the jaw-closing muscles induce muscle soreness, fatigue and functional impairment of the jaw, resembling the symptoms of myalgia, according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). However, it is claimed that repetition of similar exercises can minimise these detrimental effects. This study aimed to evaluate the response of jaw-closing muscles following two series of intense eccentric-concentric exercises of the masticatory muscles in healthy subjects. Twelve pain-free participants underwent 2 sessions of intense eccentric-concentric jaw exercises, with 1-week interval in between. Each session of jaw exercises comprises 6 sets of 5-minute-long bouts of concentric-eccentric contractions. Self-reported muscle fatigue and pain, maximum mouth opening without pain (MMO), pain pressure thresholds (PPTs) of temporalis and masseter muscles and maximum voluntary bite force (MVBF) were recorded before, immediately after, 24 and 48 hours after each bout of exercises. ANOVA for repeated measurements was used to analyse the data. During session 2, muscle pain and fatigue were statistically significantly decreased (P < .05) as compared to session 1. Furthermore, statistically significant increases of MVBF (P < .005), MMO (P < .005) and PPTs (P < .005) were found at session 2 as compared to session 1. Within the limitations of the study, is can be concluded that the repetition of eccentric-concentric jaw-closing exercises results in signs of muscle training. Future studies can elucidate whether this motor training might be useful for the treatment of myalgia.

Is there an association between various aspects of oral health in Southern Italy children? An epidemiological study assessing dental decays, periodontal status, malocclusions and temporomandibular joint function.

AIM: To describe the current oral health status of primary school children in Southern Italy, to investigate if there is an association between malocclusions and temporomandibular disorders (TMDs), and to investigate if there is an association between dental caries and periodontal disease. MATERIALS AND METHODS: Study design: Transversal epidemiological study. We examined 1086 children, considering them of the same socioeconomic status (medium). The Decayed, Missing, Filled (DMF) index and the Community Periodontal Index (CPI) were used to assess decay and periodontal status. Moreover, orthodontic and gnathologic evaluations were performed. RESULTS: Children had a mean age of 10.3±0.72 yrs, 41.6% had active dental caries in permanent teeth and 54.8% experienced periodontal problems. The 54.3% of patients had Angle Class I, 40.1% Class II and 5.5% Class III. The 13.8% of children had a deviated opening pattern of the mandible, and 2.2% of them had TMJ pain. DMF indices greater than 0 were associated with positive CPI. Males were more susceptible to periodontal disease, compared to females. TMJ pain was found associated with a decreased overbite. STATISTICS: Descriptive statistics for continuous data, and frequencies and percentages for categorical and ordinal data were calculated. Univariate linear and logistic regression model, with ? calculations, was used to assess associations between dental caries status and CPI, and between malocclusions and gnathologic aspects. CONCLUSIONS: This study found a noticeable prevalence of oral diseases among children of Southern Italy and an association between malocclusions and TMDs, periodontal disease and dental decay. Thus, a higher number of preventive interventions are recommended in the area.

Delayed-onset muscle soreness does not influence occlusal sensitivity and position sense of the mandible.

Masticatory muscle-pain patients often complain about sensorimotor changes, but the effects of pain on the psychophysical properties remain unclear. This study aimed to investigate the effects of delayed-onset muscle soreness (DOMS) on the jaw's position sense (PS) and occlusal sensitivity (OS). In all, 12 participants underwent intense concentric-eccentric jaw exercises. Self-reported muscle fatigue and pain, pain-free maximum mouth opening (MMO), pain pressure thresholds (PPTs) at right and left masseter and right and left anterior temporalis, maximum voluntary bite force (MVBF), PS and OS were recorded before, immediately after, 24 h, 48 h and 1 week after the exercises. Data were analysed with repeated measures anova. Pain and fatigue increased significantly after the exercises, while fatigue also increased 24 h afterwards. Time and site had a significant effect for PPTs, not for MVBF. MMO decreased significantly 24 h after the exercises. OS and PS did not change significantly. Experimentally induced DOMS does not influence the psychophysical properties of the masticatory system.

Skeletal and dental effects of Class III orthopaedic treatment: a systematic review and meta-analysis.

To summarise the skeletal, dental and soft tissue effects of orthopaedic treatment on growing skeletal class III patients compared with a concurrent untreated similar control group and to evaluate whether the design of the primary studies may affect the results. A literature search was performed up to the end of February 2016. No restrictions were applied concerning language and appliances. Once the quality score was assessed, a meta-analysis was performed for the appliances used in more than three studies. A moderator analysis for study design was performed. The level of evidence was evaluated by means of the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) tool. The search resulted in 21 papers. The quality of most of the studies was medium. Each study reported skeletal sagittal improvement and overjet correction. Fourteen studies reported a significant increase in lower facial height. Follow-up data showed slight relapses in about 15% of patients. Meta-analyses were performed for the facemask and chin cup. The two appliances were efficient for correcting the sagittal discrepancy, increasing the divergence. In the analysis for study design, the retrospective studies showed a more efficient appliance than RCTs for 6 of 13 variables. The level of evidence was between very low and moderate. There is very low to low evidence that orthopaedic treatment is effective in the correction of Class III skeletal discrepancies and moderate evidence for the correction of the overjet. A common side effect is mandibular clockwise rotation in older subjects.

Translation and validation of the italian version of the Psychosocial Impact of Dental Aesthetics Questionnaire (pidaq) among adolescents.

AIM: The Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) is a valid tool aiming to evaluate the self-reported influence of dental aesthetics on quality of life. This questionnaire was developed in English for young adults, and later translated and validated with an Italian population. A new version of the questionnaire was recently introduced to be used in adolescents (11-17 years- old), but it had not been translated in Italian yet. Hence, the purpose of this study was to translate, cross-culturally adapt and validate the PIDAQ for adolescents, for its use among Italian subjects. METHODS: To develop the Italian PIDAQ, the original version was translated, back-translated, cross-culturally adapted and pre-tested. Afterwards, the Italian PIDAQ was administered to a convenience sample of 677 subjects, aged 11-17 years, together with two other written questionnaires: the Aesthetic Component of the Index of Orthodontic Treatment Need (IOTN-AC) and the Perception of Occlusion Scale (POS), which are instruments dedicated to assess the self-reported degree of malocclusion. A one-way ANOVA was performed to assess the difference between groups, within each PIDAQ factor, according to POS and IOTN-AC scores. The correlation between PIDAQ factors and POS/IOTN-AC scores was measured as Spearman's rank correlation. The internal consistency was assessed as Cronbach's alpha coef?cient (α), and the test-retest reproducibility as Intra-Class Correlation Coef?cient (ICC). RESULTS: The one-way ANOVA showed that all the factors of the self- reported impact of dental aesthetics on quality of life significantly increased as the degree of malocclusion worsened (P<0.001). Furthermore, all the factors showed statistically significant correlations with both IOTN-AC and POS scores. The α ranged between 0.79 and 0.90, and the ICC ranged between 0.93-0.97. CONCLUSION: The Italian adolescent PIDAQ showed good reliability and validity. The psychometric properties of this version of the questionnaire support its use for the assessment of the psychosocial impact of dental aesthetics among Italian adolescents.

Dental and skeletal effects of palatal expansion techniques: a systematic review of the current evidence from systematic reviews and meta-analyses.

The aim was to assess the quality and to summarise the findings of the Systematic Reviews (SRs) and Meta-Analyses (MAs) on the dental and skeletal effects of maxillary expansion. Electronic and manual searches have been independently conducted by two investigators, up to February 2015. SRs and MAs on the dentoalveolar and skeletal effects of fixed expanders were included. The methodological quality was assessed using the AMSTAR (A Measurement Tool to Assess Systematic Reviews). The design of the primary studies included in each SR/MA was assessed with the LRD (Level of Research Design scoring). The evidence for each outcome was rated applying a pre-determined scale. Twelve SRs/MAs were included. The AMSTAR scores ranged from 4 to 10. Two SRs/MAs included only RCTs. The current findings from SRs/MAs support with high evidence a significant increase in the short-term of maxillary dentoalveolar transversal dimensions after Rapid Maxillary Expansion (RME). The same effect is reported with moderate evidence after Slow Maxillary Expansion (SME). However, there is moderate evidence of a non-significant difference between the two expansion modalities concerning the short-term dentoalveolar effects. With both RME and SME, significant increase of skeletal transversal dimension in the short-term is reported, and the skeletal expansion is always smaller than the dentoalveolar. Even though dental relapse to some extent is present, long-term results of the dentoalveolar effects show an increase of the transversal dimension, supported by moderate evidence for RME and low evidence for SME. Skeletal long-term effects are reported only with RME, supported by very low evidence.

Two-year survival rates of anti-TNF-α therapy in psoriatic arthritis (PsA) patients with either polyarticular or oligoarticular PsA.

OBJECTIVES: To evaluate the 2-year drug survival rates of the tumour necrosis factor (TNF)-α blockers adalimumab, etanercept, and infliximab in psoriatic arthritis (PsA) patients with either oligoarticular (oligo-PsA) or polyarticular PsA (poly-PsA). METHOD: We studied a prospective cohort of 328 PsA patients with peripheral arthritis (213 with poly-PsA and 115 with oligo-PsA), beginning their first ever anti-TNF-α treatment with adalimumab, etanercept, or infliximab. The aim of the study was to evaluate the drug survival rates and possible baseline predictors at 2 years. RESULTS: After 24 months, persistence in therapy with the first anti-TNF-α blocker was not statistically different in the oligo-PsA (70.4%) and poly-PsA (65.7%) subsets. Predictors of drug discontinuation were female sex [hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.00-2.68, p = 0.04] and starting the therapy in years 2003-8 (HR 0.51, 95% CI 0.33-0.80, p = 0.003). In poly-PsA, the persistence of etanercept (68.3%) was significantly higher than that of adalimumab (51.9%, p = 0.01), whereas in oligo-PsA no significant difference was detected. In poly-PsA, the period 2003-8 was a negative predictor (HR 0.36, 95% CI 0.21-0.62, p = 0.0001) whereas in oligo-PsA female gender was a positive predictor of drug discontinuation (HR 2.08, 95% CI 1.02-4.24, p = 0.04). With regard to clinical outcomes, the best responses in terms of European League Against Rheumatism (EULAR) 'good' response or Disease Activity Score (DAS28) remission, crude or adjusted according to the LUND Efficacy indeX (LUNDEX), were seen in patients on etanercept or infliximab. CONCLUSIONS: Our study provides some evidence that anti-TNF-α drugs may perform differently in PsA, and that the analysis of clinical disease subsets may improve our knowledge and promote better management of PsA.

Class II functional orthopaedic treatment: a systematic review of systematic reviews.

This Systematic Review (SR) aims to assess the quality of SRs and Meta-Analyses (MAs) on functional orthopaedic treatment of Class II malocclusion and to summarise and rate the reported effects. Electronic and manual searches were conducted until June 2014. SRs and MAs focusing on the effects of functional orthopaedic treatment of Class II malocclusion in growing patients were included. The methodological quality of the included papers was assessed using the AMSTAR (Assessment of Multiple Systematic Reviews). The design of the primary studies included in each SR was assessed with Level of Research Design scoring. The evidence of the main outcomes was summarised and rated according to a scale of statements. 14 SRs fulfilled the inclusion criteria. The appliances evaluated were as follows: Activator (2 studies), Twin Block (4 studies), headgear (3 studies), Herbst (2 studies), Jasper Jumper (1 study), Bionator (1 study) and Fränkel-2 (1 study). Four studies reviewed several functional appliances, as a group. The mean AMSTAR score was 6 (ranged 2-10). Six SRs included only controlled clinical trials (CCTs), three SRs included only randomised controlled trials (RCTs), four SRs included both CCTs and RCTs and one SR included also expert opinions. There was some evidence of reduction of the overjet, with different appliances except from headgear; there was some evidence of small maxillary growth restrain with Twin Block and headgear; there was some evidence of elongation of mandibular length, but the clinical relevance of this results is still questionable; there was insufficient evidence to determine an effect on soft tissues.

Effect of age and of reproductive status on reproductive indices in horse mares carrying mule pregnancies.

Mules (Equus mulus) are interspecific hybrids derived from crossing horse (Equus caballus) mares with jackasses (Equus asinus). In Italy, the production of mules is very important for the special environmental areas, where they are used as working animals, instead of the forbidden agricultural machines. Although many horse mares carry mule pregnancy successfully at term, low fertility of mares used for producing mules was reported, but limited data about reproductive efficiency in mares carrying mule pregnancy, especially when age and reproductive status are concerned, are available. Therefore, the present study aimed to assess the effect of age and of reproductive status on some reproductive indices of horse mares carrying mule pregnancy, in the final purpose to better clarify factors affecting reproductive performances in the valuable production of mules as working animals under special environmental areas in Italy. The study, performed on 96 draft mares inseminated with Martina Franca donkey semen, showed a satisfactory 89.6% 14 days PO pregnancy rate, lower pregnancy losses (19.8%) than those previously reported for mule pregnancies, leading to satisfactory foaling rates (71.9%), similar to those reported for intraspecific horse pregnancies. A clear, significant detrimental effect of mare's age on pregnancy losses, foaling rate, and on number of estrous cycles needed to achieve pregnancy, was found. Reproductive status also affected the reproductive indices, with significantly higher pregnancy losses and lower foaling rate in barren mares, reopening the question about the possible lower reproduction efficiency in horse mares carrying mule pregnancy. The present study results, although mostly descriptive, add useful information about some factors affecting reproductive performances in the valuable production of mules as working animals under special environmental areas in Italy.

Comparative characterisation of a commercial human chorionic gonadotrophin extracted from human urine with a commercial recombinant human chorionic gonadotrophin.

BACKGROUND: A commercial preparation of recombinant human chorionic gonadotrophin (r-hCG, Ovitrelle) was launched in 2001. Generally, hCG is available in two formats: human chorionic gonadotrophin (u-hCG), derived from the urine of pregnant females, and r-hCG produced by DNA based biotechnology. METHOD: The analytical characteristics of a highly purified u-hCG (Gonasi HP) were assessed and compared, for the first time, with the recombinant derived r-hCG (Ovitrelle). Gonasi HP is produced by extracting and purifying hCG from urine to obtain a specific bioactivity of 5000 IU/mg protein. Ovitrelle is produced via a recombinant derived mammalian cell line and purified to obtain a specific activity of 26 000 IU/mg. RESULTS AND CONCLUSION: It has been documented that commercially available u-hCG preparations can contain a number of urine derived protein contaminants as well as hCG related metabolites. This is also the case for Gonasi HP, where hCG related molecules and other proteins were found to be present, including epidermal growth factor (EGF) and eosinophil derived neurotoxin (EDN). It was also demonstrated that this preparation contained high levels of oxidised hCG. r-hCG was confirmed to be essentially intact hCG, free from contaminant proteins and with very low levels of oxidised hCG.

Blood volume modeling and refilling rate estimation in hemodialysis by continuous hemoglobin monitoring.

Eleven bicarbonate hemodialyses (HD) of 6 patients under constant ultrafiltration were continuously monitored with an optical Hb-meter, considered to be a marker of blood volume (BV) changes. A theoretical model was fed experimental data for prediction of blood volume and estimation of vascular parameters, and a time course of rate of refilling was extrapolated. The adequacy of the model was very good for the time course of BV prediction (r2 = 0.85-0.95, n = 11) and for plasma protein concentration (r2 = 0.83-0.86, n = 2). Parameters estimated included (mean-DS): filtration coefficient (Cf) = 0.22 (0.16) dl/min*mmHg, transcapillary hydrostatic pressure (DP) = 17.80 (3.44) mmHg and protein concentration of the refilling fluid (Cref) = 0.45 (0.30) g/dl. In conclusion our study has shown that the model chosen fits the observed BV profile well in all cases, thus the Hb data series can be used for BV dynamic modeling and for estimation of vascular parameters.

Biochemical aspects and clinical perspectives of continuous urea monitoring in plasma ultrafiltrate. Preliminary results of a multicenter study.

We tested a new biosensor for urea monitoring in the ultrafiltrate during PFD in a group of 5 hemodialyzed stable patients. The inspection of the UF-urea profile reflects the dynamical changes of the plasma urea concentration during diffusive dialysis and allows the fitting of the main mathematical models of urea kinetics. The biosensor efficiency was 98.4% on average (SD: 1.5%) at Uf fluxes varying from 45 to 55 ml/min (mean: 51 ml/min; SD: 3.2) and at Uf-urea concentrations varying from 23 to 165 mg/dl. The mean difference between Uf-urea determined by the laboratory method and Uf-urea assayed by the biosensor was -1.07 mg/dl and the 95% confidence interval ranged from -2.01 to 0.13 mg/dl. The mean difference between laboratory plasma urea and Uf-urea from the biosensor was on average -1.9 mg/dl and the estimated limits of agreement with a confidence of 95% were -3.16 and 0.64 mg/dl. Comparison between kinetic models and experimental profiles of plasma urea decrease, evaluations of recirculation and post-dialytic rebound, the role of Kt/V on-line during dialysis were the preliminary clinical applications of this biosensor.

[Acute renal failure and thrombotic microangiopathy (TM)]. / Insufficienza renale acuta e microangiopatia trombotica.

BACKGROUND: Thrombotic microangiopathy (TM) is a disorder characterized by fibrin formation and platelet aggregation in the small arteries and capillaries. Two main clinical settings are reported in association with this disorder: hemolitic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Both conditions share common findings such as microangiopathic anemia and thrombocytopenia. HUS is more frequent in children and is mainly characterized by renal symptoms, whereas PTT is dominated by neurologic abnormalities. However, in many patients, the clinical distinction between HUS and PTT is not clear; therefore, some authors consider the two syndromes as manifestations of the same entity. In children, the most common cause of HUS is an enteric infection caused by cytotoxin-producing bacteria (mainly Escherichia coli with serotype O157:H7). This toxin--the Shiga toxin--can bind to glomerular endothelial cells and stimulate the production of cytokines and the secretion of von Willebrand factor (vWf). TM may be caused by drugs such as cyclosporin, tacrolimus, mytomicin C, ticlopidine, quinine, and oral contraceptives. It may be associated with disorders of pregnancy (severe pre-eclampsia and postpartum HUS) or with systemic disorders such as systemic lupus erythematosus (SLE), antiphospholipid syndrome, systemic sclerosis, and human immunodeficiency virus (HIV) infection. Abnormalities of the gene of complement factor H have been found in familial HUS and in some sporadic cases of HUS not associated with diarrhea. Factor H abnormalities induce an uncontrolled complement activation that can activate the coagulation cascade. In familial PTT, genetic abnormalities of the cleaving metalloproteinase of fWf ADAMTS 13 have been identified. In other patients with TTP, antibodies inhibiting this enzyme have been found. As a consequence of plasma ADAMTS 13 deficiency, unusually large vWf multimers are produced. This abnormality, in the presence of an increased shear stress, stimulates platelet adhesion and aggregation. CONCLUSIONS: Knowledge of the type of causative abnormality is relevant to a therapeutic approach. Children with diarrheal HUS usually do not benefit from plasma infusion or exchange, whereas in patients with factor H or ADAMTS 13 deficiency procedures that include the administration of the lacking product and removal of the inhibiting or toxic factors, such as ultralarge vWfs, are mandatory. Potentially renal transplantation candidates should be screened for genetic defects to avoid the recurrence of TM in the graft.

Dialysis prescription in elderly hemodialysis patients.

A growing number of elderly patients have started dialytic treatment in recent years. In spite of this fact, there is very little literature on dialysis prescription in these patients. In this paper, the authors examine the single variables of Kt/V index and report on their own experience when prescribing the dialytic dose in elderly patients. Regarding dialyzer clearance (Kd), it is known that in order to obtain a high Kd we need an adequate vascular access. In our experience, with a radiocephalic fistula elderly patients showed less (but not significantly so) Qac than younger patients (738 +/- 350 ml/min versus 892 +/- 491 ml/min). We can therefore consider this type of fistula as the first vascular access in elderly patients also. As far as Kr is concerned, its rate of decline (0.4+/-0.4 ml/min/month) in these patients, excluding those with diabetes or a history of heart failure, is not different from that of younger patients. Treatment time remains a crucial point for adequacy. In order to avoid hypotensive episodes, especially in the elderly, we suggest T = 180 minutes minimum, and ultrafiltration rates should not exceed 0.6-0.8 kg/h. As regards V, it can be stated that these patients have a reduced lean body mass and total body water, and could therefore require smaller dialysis doses. However, we think that the target of Kt/V in malnourished elderly patients requires further study. What our data on Kt/V delivered to a large group of patients shows is that the elderly received the same adequate dialytic dose (Kt/V > 1.3) as that of younger patients.

Evaluation of the impact of a new synthetic vitamin E-bonded membrane on anemia and rHuEPO requirement in ESRD patients with central venous catheters: a pilot study.

In the last years, the number of hemodialysis (HD) patients with erythropoietin (rHuEPO) resistance is increasing. Probably, central venous catheters (CVCs) contribute to this resistance by inducing inflammation and oxidative stress. This study was aimed to compare vitamin E-bonded dialyzer (PSVE) versus polyethersulfone membrane. Sixteen subjects with CVCs were included in a prospective two-arm crossover 12-month study. The primary endpoints were the rHuEPO requirement and the erythropoiesis-stimulating agents (ESA) index, which was defined by the ratio between weekly EPO dosage (IU/kg/week) and Hb levels (g/dl). The mean dosages of rHuEPO to maintain hemoglobin between 10.5 and 12 g/dl were 135 ± 59 and 101 ± 57 IU/kg/week with polysulfone and PSVE, respectively (P = 0.14). The ESA indexes were 12.1 ± 5.2 and 8.7 ± 5.2 (P < 0.0001) with polysulfone and PSVE, respectively. A trend towards consensual changes in protein glycoxidation, antioxidant, and inflammatory markers was observed. In conclusion, the study suggests a role for PSVE in the reduction of ESA index in HD patients with CVCs.