Similar glycaemic control and risk of hypoglycaemia with patient- versus physician-managed titration of insulin glargine 300 U/mL across subgroups of patients with T2DM: a post hoc analysis of ITAS.

AIMS: The Italian Titration Approach Study (ITAS) demonstrated comparable HbA1c reductions and similarly low hypoglycaemia risk at 6 months in poorly controlled, insulin-naïve adults with T2DM who initiated self- or physician-titrated insulin glargine 300 U/mL (Gla-300) in the absence of sulphonylurea/glinide. The association of patient characteristics with glycaemic and hypoglycaemic outcomes was assessed. METHODS: This post hoc analysis investigated whether baseline patient characteristics and previous antihyperglycaemic drugs were associated with HbA1c change and hypoglycaemia risk in patient- versus physician-managed Gla-300 titration. RESULTS: HbA1c change, incidence of hypoglycaemia (any type) and nocturnal rates were comparable between patient- and physician-managed arms in all subgroups. Hypoglycaemia rates across subgroups (0.03 to 3.52 events per patient-year) were generally as low as observed in the full ITAS population. Small increases in rates of 00:00-pre-breakfast and anytime hypoglycaemia were observed in the ≤ 10-year diabetes duration subgroup in the patient- versus physician-managed arm (heterogeneity of effect; p < 0.05). CONCLUSIONS: Comparably fair glycaemic control and similarly low hypoglycaemia risk were achieved in almost all patient subgroups with patient- versus physician-led Gla-300 titration. These results reinforce efficacy and safety of Gla-300 self-titration across a range of phenotypes of insulin-naïve people with T2DM. CLINICAL TRIAL REGISTRATION: EudraCT 2015-001167-39.

SARS-CoV-2 infection in patients with autoimmune rheumatic diseases in northeast Italy: A cross-sectional study on 916 patients.

BACKGROUND: Whether patients with autoimmune rheumatic diseases (ARD) have a higher risk for SARS-CoV-2 infection (COVID-19) and how SARS-CoV-2 pandemic impacts on adherence to therapy has not been fully elucidated. We assessed the rate and clinical presentation of COVID-19, and adherence to therapy in a large cohort of patients with ARD followed-up in a tertiary University-Hospital in Northeast Italy. METHODS: Between April 9th and April 25th, 2020, after SARS-CoV-2 infection peak, a telephone survey investigating the impact of COVID-19 on patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), ANCA-associated vasculitis (AAV), and idiopathic inflammatory myopathies (IIM) was administered. Demographics, disease activity status, therapy, occupational exposure, and adherence to social distancing advise were also collected. RESULTS: 916 patients (397 SLE, 182 AAV, 176 SSc, 111 RA, 50 IIM) completed the survey. 148 patients developed at least one symptom compatible with COVID-19 (cough 96, sore throat 64, fever 64, arthromyalgias 59, diarrhea 26, conjunctivitis 18, ageusia/hyposmia, 18). Among the 916 patients, 65 (7.1%) underwent SARS-CoV-2 nasopharyngeal swab (18 symptomatic and 47 asymptomatic), 2 (0.21%) tested positive, a proportion similar to that observed in the general population of the Veneto region. No deaths occurred. 31 patients (3.4%) withdrew ≥1 medication, mainly immunosuppressants or biologics. Adoption of social distancing was observed by 860 patients (93.9%), including 335 (36.6%) who adopted it before official lockdown. CONCLUSIONS: COVID-19 incidence seems to be similar in our cohort compared to the general population. Adherence to therapy and to social distancing advise was high.

Italian Titration Approach Study (ITAS) with insulin glargine 300 U/mL in insulin-naïve type 2 diabetes: Design and population.

BACKGROUND AND AIMS: Fostering patient's self-managing of basal insulin therapy could improve glucose control, by removing patient's and physician's barriers to basal insulin initiation, titration and glucose monitoring. The Italian Titration Approaches Study (ITAS) aims at demonstrating non-inferiority (<0.3% margin) in efficacy of glucose control (change in glycated hemoglobin [HbA1c] after 24 weeks) by the same titration algorithm of insulin glargine 300 U/mL (Gla-300), managed by the (nurse assisted) patient versus the physician, in insulin naïve patients with Type 2 Diabetes Mellitus (T2DM), uncontrolled with previous treatments. METHODS AND RESULTS: ITAS is a phase IV, 24-week, national, multicenter, open label, randomized (1:1) parallel group study. 458 patients were enrolled, 359 randomized, and 339 completed the study, in 46 Italian centers. Baseline characteristics and previous medications of the ITT population (N = 355) are reported. Mean ± SD age, T2DM duration, HbA1c, FPG and BMI were 64.0 ± 9.8 years, 11.6 ± 7.6 years, 8.79 ± 0.65%, 170.9 ± 42.3 mg/dL, and 30.3 ± 5.6 kg/m2, respectively. Vascular and metabolic disorders were most frequent (73.8% and 58.3%, respectively). More than 90% of patients were on metformin. CONCLUSION: ITAS is the first study to compare two different managers (nurse-assisted patient vs physician) of the same titration algorithm of Gla-300 in insulin naïve patients with T2DM in unsatisfactory glucose control. This study might provide novel evidence on the efficacy/effectiveness of patient-managed titration algorithm of Gla-300 in a pragmatic setting and may reduce barriers to basal insulin initiation and its titration.

Diagnostic and prognostic role of renal histopathology in rheumatic diseases.

The objective was to evaluate renal involvement in several rheumatic diseases (i.e. rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, systemic sclerosis, systemic vasculitides). The method chosen was to define histopathological profiles reported in renal biopsies performed on patients with renal involvement due to different rheumatic diseases. Renal involvement observed in patients with rheumatic disease can be the direct result of the disease per se and/or a complication of drugs used in the disease treatment. The clinical-pathological correlations derived from the study of renal tissues can be useful for differential diagnosis, prognosis assessment and therapeutic decisions. Renal biopsy should be considered as an important tool for the management of nephropathies in patients with systemic rheumatic diseases.

Generalized annular granuloma associated with crowned dens syndrome, which resolved with colchicine treatment.

Granuloma annulare (GA) is a chronic, benign, and usually self-limiting cutaneous inflammatory disease, typically characterized by small, localized, skin-coloured papules that are usually asymptomatic or mildly pruriginous. Its aetiopathogenesis is still unknown and treatments are rarely effective. Generally, 50-70% of localized GA cases are self-limiting and show spontaneous resolution after 1-2 years, whereas disseminated GA is less likely to disappear without treatment. Treatment of generalized GA is usually based on single case reports, and only a few studies involving large case series have been published. We present the case of a patient affected by generalized GA, which resolved after colchicine treatment used for concomitant crowned dens syndrome due to calcium pyrophosphate deposition disease (CPPD). Colchicine may have worked by a direct action on GA or, alternatively, by controlling CPPD, as a possible trigger. As the low-dosage colchicine treatment was well tolerated by our patient, this could be easily used in the management of GA. However, further studies are needed to confirm the action of colchicine on GA.

Bilateral Warthin tumor in psoriatic patients in therapy with multiple immunosuppressive therapy.

Anti-TNFα drugs have strongly changed the way in which we deal with moderate and severe psoriasis. However, it is debatable whether biological drugs could increase the risk of developing cancer. The correlation between anti-TNFα drugs and lymphomas is well-known and is reported in all the technical details of biologic drugs. However, the association between anti-TNFα agents and solid tumors is still controversial. The authors report a case of bilateral salivary gland tumor in a psoriatic patient treated with several immunosuppressive therapies including anti-TNFα inhibitors.

Heavy-ion anisotropy measured by ALTEA in the International Space Station.

The uneven shielding of the International Space Station from the vessel hull, racks and experiments produces a modulation of the internal radiation environment. A detailed knowledge of this environment, and therefore of the Station's shielding effectiveness, is mandatory for an accurate assessment of radiation risk. We present here the first 3D measurements of the Station's radiation environment, discriminating particle trajectories and LET, made possible using the detection capability of the ALTEA-space detector. We provide evidence for a strong (factor ≈ 3) anisotropy in the inner integral LET for high-LET particles (LET > 50 keV/µm) showing a minimum along the longitudinal station axis (most shielded) and a maximum normal to it. Integrating over all measured LETs, the anisotropy is strongly reduced, showing that unstopped light ions plus the fragments produced by heavier ions approximately maintain flux/LET isotropy. This suggests that, while changing the quality of radiation, the extra shielding along the station main axis is not producing a benefit in terms of total LET. These features should be taken into account (1) when measuring radiation with detectors that cannot distinguish the direction of the impinging radiation or that are unidirectional, (2) when planning radiation biology experiments on the ISS, and (3) when simulating the space radiation environment for experiments on the ground. A novel analysis technique that fully exploits the ability to retrieve the angular distribution of the radiation is also presented as well as the angular particle flux and LET characteristic of three geomagnetic zones measured during 2009 by the ALTEA-space detector. This technique is applied to the ALTEA-space detector, but a wider applicability to other detectors is suggested.

Comparative evaluation of synergy of combinations of beta-lactams with fluoroquinolones or a macrolide in Streptococcus pneumoniae.

OBJECTIVES: Streptococcus pneumoniae has shown a great ability to develop efficacious mechanisms of resistance to the main drugs for the treatment of pneumonia, such as ß-lactams, macrolides and fluoroquinolones. The present study aimed to compare the antipneumococcal activity of combinations of respiratory fluoroquinolones with cephalosporins (either parenteral or oral) or protected penicillin versus the standard combinations (i.e. a macrolide with a protected penicillin or cephalosporin) against 100 isolates with different susceptibilities to macrolides and/or penicillin. METHODS: Chequerboard assays for all isolates and time-kill curves for nine isolates with different patterns of susceptibility were performed. Synergy between antibiotics at serum peak concentrations was also determined. RESULTS: The combination of levofloxacin with ceftriaxone produced the highest rate of synergy (54/100), mainly against macrolide-resistant strains (22/30). Antagonism was not observed for any tested combination apart from clarithromycin with amoxicillin/clavulanic acid (22/100 isolates). Although the killing activities of all antibiotics improved when they were tested in combination, synergy was observed only for some combinations after 12 and/or 24 h. Serum concentrations were effective in inhibiting the growth of the tested strains. CONCLUSIONS: Combinations of levofloxacin with parenteral cephalosporins were the most active among all the tested combinations, while antagonism occurred when clarithromycin and amoxicillin/clavulanic acid were tested.

[Endometriosis: aetiopathogenetic basis]. / Endometriosi: le basi eziopatogenetiche.

Endometriosis, defined by the presence of endometrial tissue outside the uterine cavity, is a common condition affecting 10% of women in the reproductive age. Menstrual factors reported to increase risk include dysmenorrhea, early menarche, and shorter cycle lengths. The theory of retrograde menstruation with implantation of endometrial fragments, in conjunction with peritoneal factors to stimulate cell growth is the most widely accepted. There is a growing body of evidence that immunological factors and angiogenesis play a key role in the pathogenesis of endometriosis. In women with endometriosis, there appears to be an alteration in the function of peritoneal macrophages, natural killer cells and lymphocytes, with production of growth factors and inflammatory mediators in the peritoneal fluid. Survival, adhesion, proliferation, invasion and vascularization of endometrial tissue in abdominal cavity may be the consequence of retrograde menstruation and referred to as implantation theory.

Specific immunotherapy for allergic rhinitis in Italy: the patients points of view.

Specific immunotherapy (SIT) is the unique causal treatment for allergy, but its use is quite limited. A perspective, cross-sectional telephone interview survey was carried out in Italy to evaluate the characteristics of 500 patients with allergic rhinitis (250 of whom treated with SIT). Relevant differences were found concerning therapeutic management of allergic rhinitis, mainly regarding the use of drugs and co-morbidities. The allergist is the most important consultant who prescribes SIT. This study therefore provides evidence that the course of allergic rhinitis may depend on the therapy prescribed by and the level of allergy awareness of the physician.

Specific immunotherapy for allergic rhinitis in Italy: the doctors points of view.

Specific immunotherapy (SIT) is the unique causal treatment for allergy, but its prescription is quite restricted. A perspective and cross-sectional survey based on telephone interviews was carried out in Italy to evaluate the profile of doctors prescribing SIT for allergic rhinitis. A total of 540 doctors were interviewed, 200 of whom are GPs, 60 allergists, 60 ENT specialists, 100 familial paediatricians, 60 hospital paediatricians and 60 pulmonologists. Significant differences concern diagnostic and therapeutic management of allergic rhinitis, mainly regarding SIT prescription. The allergist is the most important consultant who prescribes SIT, as opposed to the paediatrician. This study therefore provides the evidence that doctors behaviour towards SIT depends on the type of graduate studies.

Doctors' and patients' educational levels affect immunotherapy prescription.

Cultural level appears to be a critical factor in the decision process of allergen-specific immunotherapy (SIT) both for doctors and patients. Thus, appropriate educational programs should be carried out to increase the number of allergic patients to be treated with SIT.

Prevalence of nosocomial infections in 15 Italian hospitals: first point prevalance study for the INF-NOS project.

BACKGROUND: The aim of our study was to assess the magnitude of nosocomial infections (NI) in 15 Italian hospitals. PATIENTS AND METHODS: A multicenter point prevalence study of NI was carried out in October 2001 among eight medical, surgical and intensive care units in hospitals with more than 400 beds, after a pilot phase performed in April 2001. RESULTS: Of the 2,165 surveyed patients, 163 had a total of 179 NIs. The global prevalence rate of patients with NI and of NI was respectively 7.5% (95% CI 6.4-8.6) and 8.3% (95% CI 7.1-9.4), ranging from 5.5% (95% CI 4.2-6.8) in medical wards to 34.2% (95% CI 25.7-42.7) in intensive care units (ICUs). The NI prevalence was higher in: hospitals that did not have an infection control committee (ICC) compared to hospitals with an ICC (10.3%, 95% CI 6.4-10.1 versus 7.2, 95% CI 6.0-8.3, p = 0.08); university hospitals compared with non-teaching hospitals (9.4%, 95% CI 4.5-14.2 versus 7.4%, 95% CI 6.3-8.5, p = 0.4) and; hospitals with 1,000 or more beds compared to lower volume hospitals (9.5%, 95% CI 7.3-11.7 versus 6.6%, 95% CI 5.3-7.8, p = 0.02). The most prevalent infections found were lower respiratory tract infections, urinary tract infections and surgical-site infections, representing 38.0%, 20.1% and 12.8%, respectively, of all NI. Among 1,674 patients without any infection, 575 (34.3%) of them had been undergoing antibiotic treatment at the time of the survey. CONCLUSION: The high rate of NI, particularly in ICUs, and the high number of improper procedures emphasize the need to develop clinically-oriented guidelines, tailor active infection control programs and implement an active ICU surveillance system.

Prevalence and patterns of antibiotic prescribing in Italian hospitals.

Use of antimicrobial drugs is associated with the emergence of resistant bacteria, increasing hospital expenditures and requires an assessment of appropriateness. The aim of this study was to investigate prevalence and patterns of antibiotic prescribing and expenditures in Italian hospitals. A prevalence survey was performed in 15 Italian hospitals. Data on antimicrobial use and expenditures in the year 2000 and 1-day point prevalence information on antibiotic prescription, type and sources of infections and expenditures were obtained through a review of pharmacy records and charts of 2,165 inpatients. 45.5% of the patients surveyed were receiving at least one antibiotic: 148 for hospital-acquired infections (HAI), 262 for community-acquired infections (CAI). No active infection was recorded for 575 patients (58.4%). 57.3% of prescriptions for HAI and 65.9% for CAI were based on empiric and presumptive criteria, while 39% of HAI and 15.8% of CAI were oriented by microbiology and susceptibility testing results. Guidelines were followed in choosing the antimicrobial drugs for 22.8% of therapeutic and 46.8% of prophylactic courses. High rates of antibiotic usage were observed in Italian hospitals. Areas for improvement, both for the use of diagnostic resources and the prescribing habits, were identified. The 1-day prevalence survey of antimicrobial use may be a tool of feedback to prescribers for more appropriate drug selection.

Citric acid demineralization and subepithelial connective tissue grafts.

BACKGROUND: The present study was designed to evaluate the effect, if any, of citric acid root demineralization in the outcome of subepithelial connective tissue grafts performed to cover localized gingival recessions. METHODS: Thirty-six patients participated, each providing one gingival recession; 19 received citric acid demineralization, while 17 did not. All were treated surgically with subepithelial connective tissue grafts and followed for 6 months. At baseline and 6 months, the following parameters were recorded: plaque index, gingival index, recession height, probing depth, recession width, and amount of keratinized tissue. Data were analyzed statistically to 1) evaluate the results achieved with each procedure individually over time and 2) compare the results obtained with the 2 procedures after 6 months. RESULTS: Results showed significant reductions in recession height after 6 months independently of whether citric acid was applied or not (2.79+/-0.79 versus 2.56+/-0.73). Similarly, recession width was significantly reduced (3.74+/-1.19 versus 3.50 +/-0.73), and the width of keratinized tissue was significantly increased (2.47+/-1.6 versus 2.3+/-1.2). No significant changes in probing depth were found (-0.16+/-0.06 versus -0.13+/-0.81). No significant differences were found when both techniques were compared in any one of the parameters analyzed (all P >0.30). CONCLUSIONS: It is concluded that: 1) the subepithelial connective tissue graft procedure provides a satisfactory solution in the treatment of localized gingival recessions, and 2) citric acid demineralization does not affect the clinical outcome of the surgical technique.

Clinical and histologic evaluation of submerged and nonsubmerged hydroxyapatite-coated implants: a preliminary study in dogs.

A clinical and histologic study was performed to evaluate the differences in the healing of submerged and nonsubmerged hydroxyapatite-coated 2-piece implants. Three foxhounds were used for this evaluation. Mandibular premolars 1, 2, 3, and 4 were extracted. Three months later, 2 submerged implants were placed on one side of the mandible, and 2 nonsubmerged implants were placed on the other side of the mandible. After 3 months of healing, the submerged implants were exposed, and a third implant was placed on each side of the mandible in a nonsubmerged procedure. Clinical parameters were recorded, the animals were sacrificed 6 months after placement of the first implants, and histologic and histometric analyses were performed. Results of the evaluation of the clinical parameters showed only minor differences among the different treatment groups. Regarding the percentage of bone-to-implant contact of the different treatment groups, the submerged implants showed a bone-to-implant contact of 63.4%, the nonsubmerged implants showed 70.3% contact, and the late nonsubmerged implants demonstrated a bone-to-implant contact of 58.7%. The average distance from the implant neck to the first bone-to-implant contact (fBIC) for submerged implants was 0.58 mm, for nonsubmerged implants it was 1.09 mm, and it was 1.13 mm for late nonsubmerged implants. The vertical distance between the gingival margin and the apical extent of the junctional epithelium (aJE) varied from 1.14 mm to 1.28 mm in the different groups. The distance from the aJE to fBIC was 1.00 mm for the submerged group, 1.08 mm for the nonsubmerged group, and 1.00 mm for the late nonsubmerged group. Generally, it can be concluded that the clinical and the histologic behavior of submerged or nonsubmerged 2-piece implants utilized in this experiment do not differ.