The use of antiemetics for vomiting in acute gastroenteritis in children is still a matter of debate. We conducted a double-blind randomized trial to evaluate whether a single oral dose of ...ondansetron vs domperidone or placebo improves outcomes in children with gastroenteritis. After failure of initial oral rehydration administration, children aged 1-6 years admitted for gastroenteritis to the pediatric emergency departments of 15 hospitals in Italy were randomized to receive one oral dose of ondansetron (0.15 mg/kg) or domperidone (0.5 mg/kg) or placebo. The primary outcome was the percentage of children receiving nasogastric or intravenous rehydration. A p value of 0.014 was used to indicate statistical significance (and 98.6% CI were calculated) as a result of having carried out two interim analyses. 1,313 children were eligible for the first attempt with oral rehydration solution, which was successful for 832 (63.4%); 356 underwent randomization (the parents of 125 children did not give consent): 118 to placebo, 119 to domperidone, and 119 to ondansetron. Fourteen (11.8%) needed intravenous rehydration in the ondansetron group vs 30 (25.2%) and 34 (28.8%) in the domperidone and placebo groups, respectively. Ondansetron reduced the risk of intravenous rehydration by over 50%, both vs placebo (RR 0.41, 98.6% CI 0.20-0.83) and domperidone (RR 0.47, 98.6% CI 0.23-0.97). No differences for adverse events were seen among groups. In a context of emergency care, 6 out of 10 children aged 1-6 years with vomiting due to gastroenteritis and without severe dehydration can be managed effectively with administration of oral rehydration solution alone. In children who fail oral rehydration, a single oral dose of ondansetron reduces the need for intravenous rehydration and the percentage of children who continue to vomit, thereby facilitating the success of oral rehydration. Domperidone was not effective for the symptomatic treatment of vomiting during acute gastroenteritis.
Objective. This study was aimed at assessing the long-term ocular control of adalimumab (ADA) in a large real-world population with noninfectious primary or secondary uveitis, focusing on the ...steroid-sparing effect and on disease-modifying antirheumatic drug (DMARD) cotreatment. Methods. In this retrospective, multicenter study, the efficacy of ADA was evaluated in terms of ocular control, changes in best-corrected visual acuity (BCVA), corticosteroid-sparing effect, and drug retention rate, overall and stratified according to DMARD cotreatment. Results. 106 patients were included. 88.7% had an associated systemic disease. After 6 and 12 months, proportions of patients with effective ocular control were 83.7% and 83.3%, respectively. At last the follow-up, 94.6% of patients had satisfactory ocular control. No difference in terms of ocular control at all time points emerged among patients starting ADA for ocular vs. systemic involvements. Patients with poor baseline BCVA remained stable or improved, while those with good BCVA hardly worsened. At 6 and 12 months, the median dose of prednisone significantly reduced to 5 mg/day (0-5) and 2.5 mg/day (0-5) (p<0.001). Over a median follow-up of 36 months, 38 subjects discontinued ADA treatment. Mild to moderate side effects were reported in 7 patients (6.6%). ADA ocular control, corticosteroid-sparing effect, and drug retention rate were not influenced by the concomitant use of DMARDs. Conclusion. The long-term ocular control of ADA in noninfectious primary or secondary uveitis is confirmed, also for BCVA preservation. Concomitant use of DMARDs does not provide additional benefits to ADA alone in terms of ocular control, steroid spare, and drug retention rate.
The aim of the present study was to compare long-term adalimumab (ADA) and infliximab (IFX) retention rates in patients with intermediate, posterior, or panuveitis. Additional aims are as follows: ...(i) to identify any difference in the causes of treatment discontinuation between patients treated with ADA and IFX; (ii) to assess any impact of demographic features, concomitant treatments, and different lines of biologic therapy on ADA and IFX retention rates; and (iii) to identify any correlation between ADA and IFX treatment duration and the age at uveitis onset, the age at onset of the associated systemic diseases, and the age at the start of treatment. Clinical, therapeutic, and demographic data from patients with non-infectious intermediate, posterior, or panuveitis treated with ADA or IFX were retrospectively collected. Kaplan-Meier plot and log-rank (Mantel-Cox) test were used to assess survival curves. One hundred eight patients (188 eyes) were enrolled; in 87 (80.6%) patients, uveitis was associated with a systemic disease. ADA and IFX were administered in 62 and 46 patients, respectively. No statistically significant differences were identified between ADA and IFX retention rates (
p
value = 0.22). Similarly, no differences were identified between ADA and IFX retention rates in relation to gender (
p
value = 0.61 for males,
p
value = 0.09 for females), monotherapy (
p
value = 0.08), combination therapy with conventional disease-modifying antirheumatic drugs (log-rank
p
value = 0.63), and different lines of biologic therapy (
p
value = 0.79 for biologic-naïve patients;
p
value = 0.81 for subjects previously treated with other biologics). In conclusion, ADA and IFX have similar long-term retention rates in patients with non-infectious intermediate, posterior, and panuveitis. Demographic, clinical, and therapeutic features do not affect their long-term effectiveness.
To identify a set of variables that could discriminate patients with adult-onset periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome from subjects with fever of ...unknown origin (FUO).
We enrolled 74 adults diagnosed with PFAPA syndrome according to the currently used pediatric diagnostic criteria and 62 additional patients with FUO. After having collected clinical and laboratory data from both groups, univariate and multivariate analyses were performed to identify the variables associated with PFAPA diagnosis. Odds ratio (OR) values, their statistical significance, and corresponding 95% confidence interval (CI) were evaluated for each diagnostic factor both at the univariate and multivariate analyses. Diagnostic accuracy was evaluated by the area under receiver operating characteristic (ROC) curve, while the leave-one-out cross-validation procedure was used to ensure that the model maintains the same diagnostic power when applied to new data.
According to the multivariate analysis, the clinical variables that discriminated PFAPA patients were: fever episodes associated with cervical lymphadenitis (OR = 92;
< 0.0001), fever attacks associated with erythematous pharyngitis (OR = 231;
< 0.0001), increased inflammatory markers during fever attacks (OR = 588;
= 0.001), and the lack of clinical and laboratory signs of inflammation between flares (OR = 1202;
< 0.0001). These variables were considered for a diagnostic model which accounted for their OR values. The diagnostic accuracy of the proposed set of criteria corresponded to an area under ROC curve of 0.978 (95% CI 0.958-0.998), with a model sensitivity and specificity equal to 93.4% (95% CI 87.5-96.5%) and 91.7% (95% CI 82.8-96.7%), respectively.
we have provided herein a set of clinical diagnostic criteria for adult-onset PFAPA syndrome. Our criteria represent an easy-to-use diagnostic tool aimed at identifying PFAPA patients among subjects with FUO with a high-predictive potential, as shown by its very high sensitivity and specificity.
Objectives. To examine demographic and clinical characteristics and long-term visual outcome in a cohort of Italian patients affected by Behçet’s uveitis (BU). Materials and Methods. Retrospective ...chart review of 47 patients with BU attending our unit between January 2018 and December 2019. Ophthalmologic manifestations, best-corrected visual acuity (BCVA), fluoroangiography and optical coherence tomography findings, and ocular complications were recorded. Predictive factors of a poor visual outcome and long-term complications were also investigated. Results. Forty-seven patients (23 males and 24 females) for a total of 84 eyes were enrolled. Uveitis was bilateral in 37 (78.7%) patients with panuveitis being the most frequent anatomical pattern (40 out of 84 eyes), whereas 27 eyes presented a posterior uveitis. Isolated anterior uveitis was detected in 16 eyes. A significant improvement of median BCVA between baseline and last follow-up values was detected (p=0.042). A higher risk of poor visual prognosis was observed in patients with uveitis duration greater than 15 years (p=0.019). A significant resolution of retinal vasculitis was detected between baseline and last follow-up evaluation (p<0.0001) whereas the mean±SD macular thickness did not decrease significantly between baseline (376.00±97.45 μm) and last follow-up evaluation (338.08±55.81 μm). Forty-two eyes developed 57 complications during the disease course. Cataract was the most frequent (n=12), followed by epiretinal membranes (n=11) and cystoid macular edema (n=6). The following variables were identified as predictors of long-term complications: human leukocyte antigen- (HLA-) B51 (p=0.006), panuveitis (p=0.037), and a uveitis duration of more than 15 years (p=0.049). Conclusions. In Italian patients, BU typically arises in the third decade and predominantly manifests as a bilateral posterior uveitis or panuveitis. Its duration is associated with a poor visual prognosis. Uveitis duration, the presence of HLA-B51, and panuveitis are predictors of long-term structural complications, thus representing main drivers in the treatment decision-making.
The purpose of the present study was to describe our experience with the recombinant Fab' antibody fragment against TNF-α Certolizumab Pegol (CZP) in patients with Behçet's disease (BD) refractory to ...standardized therapies and previous biologic agents.
Retrieved data including demographic characteristics, clinical manifestations, and previous treatments were collected in three different specialized Rheumatologic Units in Italy. In order to evaluate disease activity, the BD current activity form (BDCAF) has been used before starting CZP therapy and at each visit during treatment.
Thirteen BD patients (mean age 42.6 ± 8.8 years) with a disease duration of 8.80 ± 6.9 years, underwent CZP treatment for 6.92 ± 3.52 months. Six patients (46.15%) experienced a worsening of symptoms after 4.16 ± 1.21 months, whereas a satisfactory response was achieved in seven patients (53.84%) who were still on CZP therapy at the last follow-up visit (after 9.28 ± 3.03 months of treatment). The mean decrease of BDCAF between the first and last visit was 0.308 ± 1.84 without reaching significant difference (mean 8.3 ± 1.3 and 8 ± 2.08, respectively; p= .51). During the whole study period, CZP was well tolerated in all patients except one who developed a generalized cutaneous reaction after the third administration.
These results suggest that despite an improvement of clinical manifestations has been observed in more than half of the patients, it is not possible to draw firm conclusions about the effectiveness of CZP in BD and further studies with larger cohorts of patients are warranted. Whether the increase of CZP dosage may ensure a better clinical response remains an unsolved issue that needs to be considered.
(1) Background: Genitourinary syndrome of menopause (GSM) is a medical condition that can affect breast cancer survivors (BCS). This is a complication that often can occur as a result of breast ...cancer treatment, causing symptoms such as vaginal dryness, itching, burning, dyspareunia, dysuria, pain, discomfort, and impairment of sexual function. BCS who experience these symptoms negatively impact multiple aspects of their quality of life to the point that some of them fail to complete adjuvant hormonal treatment; (2) Methods: In this systematic review of the literature, we have analyzed possible pharmacological and non-pharmacological treatments for GSM in BCS. We reviewed systemic hormone therapy, local hormone treatment with estrogens and androgens, the use of vaginal moisturizers and lubricants, ospemifene, and physical therapies such as radiofrequency, electroporation, and vaginal laser; (3) Results: The data available to date demonstrate that the aforementioned treatments are effective for the therapy of GSM and, in particular, vulvovaginal atrophy in BCS. Where possible, combination therapy often appears more useful than using a single line of treatment; (4) Conclusions: We analyzed the efficacy and safety data of each of these options for the treatment of GSM in BCS, emphasizing how often larger clinical trials with longer follow-ups are needed.
This study explores demographic, clinical, and therapeutic features of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a cohort of 80 patients recruited from 19 Italian ...referral Centers. Patients’ data were collected retrospectively and then analyzed according to age groups (disease onset before or after 16 years) and genotype (high penetrance (HP) and low penetrance (LP) TNFRSF1A gene variants). Pediatric- and adult-onset were reported, respectively, in 44 and 36 patients; HP and LP variants were found, respectively, in 32 and 44 cases. A positive family history for recurrent fever was reported more frequently in the pediatric group than in the adult group (p<0.05). With reference to clinical features during attacks, pericarditis and myalgia were reported more frequently in the context of adult-onset disease than in the pediatric age (with p<0.01 and p<0.05, respectively), while abdominal pain was present in 84% of children and in 25% of adults (p<0.01). Abdominal pain was significantly associated also to the presence of HP mutations (p<0.01), while oral aphthosis was more frequently found in the LP variant group (p<0.05). Systemic amyloidosis occurred in 25% of subjects carrying HP variants. As concerns laboratory features, HP mutations were significantly associated to higher ESR values (p<0.01) and to the persistence of steadily elevated inflammatory markers during asymptomatic periods (p<0.05). The presence of mutations involving a cysteine residue, abdominal pain, and lymphadenopathy during flares significantly correlated with the risk of developing amyloidosis and renal impairment. Conversely, the administration of colchicine negatively correlated to the development of pathologic proteinuria (p<0.05). Both NSAIDs and colchicine were used as monotherapy more frequently in the LP group compared to the HP group (p<0.01). Biologic agents were prescribed to 49 (61%) patients; R92Q subjects were more frequently on NSAIDs monotherapy than other patients (p<0.01); nevertheless, they required biologic therapy in 53.1% of cases. At disease onset, the latest classification criteria for TRAPS were fulfilled by 64/80 (80%) patients (clinical plus genetic items) and 46/80 (57.5%) patients (clinical items only). No statistically significant differences were found in the sensitivity of the classification criteria according to age at onset and according to genotype (p<0.05). This study describes one of the widest cohorts of TRAPS patients in the literature, suggesting that the clinical expression of this syndrome is more influenced by the penetrance of the mutation rather than by the age at onset itself. Given the high phenotypic heterogeneity of the disease, a definite diagnosis should rely on both accurate working clinical assessment and complementary genotype.
Recent expiry of patents for tumor necrosis factor (TNF)-α inhibitors has led to the employment of biosimilars in clinical practice. The aim of the study was to identify any change in the control of ...ocular inflammatory manifestations among patients with non-infectious uveitis switching from an originator to a corresponding anti-TNF-α biosimilar.
Thirty-seven consecutive patients (62 eyes involved) with non-infectious uveitis undergoing the switch from anti-TNF-α originators to biosimilars were retrospectively enrolled; the frequency of ocular flares before and after the switch as well as best corrected visual acuity (BCVA), central macular thickness (CMT), daily systemic corticosteroid intake, and frequency of uveitic macular edema (UME) at the switch and at the following assessments were statistically analysed.
The number of ocular flares during the 12 months preceding the switch was 16, corresponding to 3.6 flares/100 patients/12 months; the number of flares after the switch was 14, corresponding to 2.0 flares/100 patients/12 months. No statistically significant differences were identified in the frequency of flares (
= 0.84) and in the number of patients experiencing ocular flares (
= 0.39) between the twelve months preceding the switch and the period thereafter. No statistically significant changes were observed in the BCVA (
= 0.27), CMT (
= 0.50), frequency of UME (
= 0.57) and daily corticosteroid intake (
= 0.42) between the time of the switch and the last follow-up visit.
The switch to biosimilars represents a feasible treatment choice associated with the maintenance of clinical efficacy in patients with non-infectious uveitis previously treated with the corresponding originator anti-TNF-α biologic agents.
Abstract Objective To analyze the clinical manifestations and response to treatment in a cohort of adult patients presenting with recurrent inflammatory attacks and carrying low-penetrance TNFRSF1A ...variants, as well as to provide data on their long-term follow-up. Methods We performed a retrospective chart review of 36 patients carrying low-penetrance TNFRSF1A variants. Moreover, 60 genetically negative patients treated for recurrent inflammatory attacks and 13 patients with structural TNFRSF1A mutations were also analyzed. Detailed demographic and clinical data were collected at the time of molecular screening and at each follow-up visit. Treatments and markers of inflammation were also assessed. Results Individuals with low-penetrance TNFRSF1A variants have a lower family history for inflammatory attacks and present with a later disease onset compared with patients with structural mutations, but do not differ, in this respect, with genetically negative individuals. Moreover, low-penetrance variants are less frequently associated with a chronic disease course, with clinical manifestations such as abdominal pain and myalgia, and with amyloidosis. A distinctive clinical feature is a higher rate of pericarditis. Interestingly, mutation-negative patients were found to present with a significant history of recurrent pharyngitis during childhood. Patients with low-penetrance variants are mostly managed with short courses of steroids or non-steroidal anti-inflammatory drugs on attacks. Although the need for a biological treatment is significantly lower compared with patients with structural mutations, still approximately 20% of individuals with recurrent inflammatory attacks carrying low-penetrance variants ultimately require these therapies. Conclusions Our study confirms that low-penetrance TNFRSF1A variants can be associated with an autoinflammatory phenotype. Although a chronic disease course is rarely observed, some patients ultimately benefit from a biological treatment.
PDF
