Introduction: Antiepileptic drugs (AEDs) are administered orally for chronic use. Parenteral formulations might be necessary when the oral route is not feasible (e.g. an impairment of consciousness, ...trauma, dysphagia, gastrointestinal illness) or for treatment of seizure emergencies. At present, few intravenous (IV) formulations are available on the market.
Areas covered: The purpose of this review is to summarize the pharmacological characteristics and clinical applications of IV medications that have been recently introduced to the armamentarium of epilepsy therapy or are currently being developed. Apart from AEDs, other compounds belonging to different pharmacological classes (e.g. diuretics, anesthetics), which have shown potential effectiveness in seizure control, are taken into consideration, and the pathophysiological premises supporting their use for epilepsy treatment are illustrated. The authors give particular focus to immunomodulatory and immunosuppressive agents, which have become the therapeutic cornerstones for immune-mediated epilepsies, despite regulatory obstacles.
Expert opinion: In several circumstances, especially in the case of seizure-related emergencies, clinical practice seems not match literature-based evidence, and several IV AEDs are still used off-label. Strong evidence derived from randomized clinical trials (RCTs) is needed to support the effectiveness and tolerability of any therapeutic approach, however common and "accepted' it may be, in order to guarantee patient safety and well-being.
Introduction
Studies on the durability of an intensive, structured education protocol on best insulin injection practice are missing for people with type 2 diabetes mellitus (T2DM). The aim of this ...study was to assess the durability of an intensive, structured education-based rehabilitation protocol on best insulin injection practice in well-trained subjects from our previous intensive, multimedia intervention study registered as the ISTERP-1 study. A total of 158 subjects with T2DM from the well-trained group of the 6-month-long ISTERP-1 study, all of whom had successfully attained lower glucose levels compared to baseline levels with lower daily insulin doses and with less frequent and severe hypoglycemic episodes, participated in the present investigation involving an additional 6-month follow-up period, called the ISTERP-2 study.
Methods
Participants were randomized into an intervention group and a control group, depending on whether they were provided or not provided with further education refresher courses for 6 months. At the end of the 6 months, the two groups were compared in terms of injection habits, daily insulin dose requirement, number of severe or symptomatic hypoglycemic events, and glycated hemoglobin (HbA1c) levels.
Results
Despite being virtually superimposable at baseline, the two groups behaved quite differently during the follow-up. The within-group analysis of observed parameters showed that the subjects in the intervention group maintained and even improved the good behavioral results learned during the ISTERP-1 study by further reducing both the rate of injection technique errors (
p
< 0.001) and size of lipohypertrophic lesions at injection sites (
p
< 0.02). Conversely, those in the control group progressively abandoned best practice, except for the use of ice-cold insulin and, consequently, had significantly higher HbA1c levels and daily insulin dose requirements at the end of the follow-up than at baseline (
p
< 0.05). In addition, as expected from all the above, the rate of hypoglycemic episodes also decreased in the intervention group (
p
< 0.05), resulting in a significant difference between groups after 6 months (
p
< 0.02).
Conclusion
Our data provide evidence that intensive, structured education refresher courses have no outstanding durability, so that repeated refresher courses, at least at 6-month intervals, are needed to have positive effects on people with T2DM, contributing not only to prevention but also to long-term rehabilitation.
Trial Registration
Trial Registration no. 118 bis/15.04.2018.
Purpose
Mixed cryoglobulinemia syndrome (MCs) is a rare immunoproliferative systemic disorder with cutaneous and multiple organ involvement. Our multicenter survey study aimed to investigate the ...prevalence and outcome of COVID-19 and the safety and immunogenicity of COVID-19 vaccines in a large MCs series.
Methods
The survey included 430 unselected MCs patients (130 M, 300 F; mean age 70 ± 10.96 years) consecutively collected at 11 Italian referral centers. Disease classification, clinico-serological assessment, COVID-19 tests, and vaccination immunogenicity were carried out according to current methodologies.
Results
A significantly higher prevalence of COVID-19 was found in MCs patients compared to Italian general population (11.9% vs 8.0%,
p
< 0.005), and the use of immunomodulators was associated to a higher risk to get infected (
p
= 0.0166). Moreover, higher mortality rate was recorded in MCs with COVID-19 compared to those without (
p
< 0.01). Patients’ older age (≥ 60 years) correlated with worse COVID-19 outcomes. The 87% of patients underwent vaccination and 50% a booster dose. Of note, vaccine-related disease flares/worsening were significantly less frequent than those associated to COVID-19 (
p
= 0.0012). Impaired vaccination immunogenicity was observed in MCs patients compared to controls either after the first vaccination (
p
= 0.0039) and also after the booster dose (
p
= 0.05). Finally, some immunomodulators, namely, rituximab and glucocorticoids, hampered the vaccine-induced immunogenicity (
p
= 0.029).
Conclusions
The present survey revealed an increased prevalence and morbidity of COVID-19 in MCs patients, as well an impaired immunogenicity even after booster vaccination with high rate of no response. Therefore, MCs can be included among frail populations at high risk of infection and severe COVID-19 manifestations, suggesting the need of a close monitoring and specific preventive/therapeutical measures during the ongoing pandemic.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Autoimmune systemic diseases (ASD) show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed at evaluating the seroconversion elicited by COVID-19 ...vaccine over the entire vaccination cycle including the booster dose. Among 478 unselected ASD patients originally evaluated at the end of the first vaccination cycle (time 1), 344 individuals were re-evaluated after a 6-month period (time 2), and 244 after the booster vaccine dose (time 3). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was assessed by measuring serum IgG-neutralizing antibody (NAb) on samples obtained at the three time points in both patients and 502 age-matched controls. In the 244 ASD group that received booster vaccine and monitored over the entire follow-up, the mean serum NAb levels (time 1, 2, and 3: 696.8 ± 52.68, 370.8 ± 41.92, and 1527 ± 74.16SD BAU/mL, respectively; p < 0.0001) were constantly lower compared to controls (p < 0.0001), but they significantly increased after the booster dose compared to the first two measurements (p < 0.0001). The percentage of patients with absent/suboptimal response to vaccine significantly decreased after the booster dose compared to the first and second evaluations (time 1, 2, and 3: from 28.2% to 46.3%, and to 7.8%, respectively; p < 0.0001). Of note, the percentage of patients with absent/suboptimal response after the booster dose was significantly higher compared to controls (19/244, 7.8% vs 1/502, 0.2%; p < 0.0001). Similarly, treatment with immune-modifiers increased the percentage of patients exhibiting absent/suboptimal response (16/122, 13.1% vs 3/122, 2.46%; p = 0.0031). Overall, the above findings indicate the usefulness of booster vaccine administration in ASD patients. Moreover, the persistence of a significantly higher percentage of individuals without effective seroconversion (7.8%), even after the booster dose, warrants for careful monitoring of NAb levels in all ASD patients to identify those with increased risk of infection. In this particularly frail patients' setting, tailored vaccination and/or therapeutic strategy are highly advisable.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The aims of this review are to analyze the current literature regarding the characteristics and pathophysiological mechanisms of itch in chronic wounds, to assess the impact on quality of life and ...delayed-healing, to focus on the best strategies of prevention and treatment, to highlight the importance of on-going research in order to fully understand the pathophysiology, and to improve the management of target therapies.
A systematic literature review was performed using MEDLINE, PubMed, Embase, Scopus, ScienceDirect, and the Cochrane Library. We included a total of 11 articles written in English with relevant information on the pathophysiology of itch in chronic wounds and on management strategies.
Itch in chronic wounds was found to be correlated with xerosis, larger wound areas, necrotic tissue and amount of exudate, peripheral tissue edema, sclerosis, granulation tissue, contact dermatitis, and bacterial burden, as well as with lower quality of life.
Although there are several aspecific pharmacological and non-pharmacological approaches, there appears to be no validated prevention or management strategy for itch in chronic wounds. Further studies are needed to clarify the association and pathophysiology of itch in chronic wounds, to evaluate the safety and efficacy of topical treatments on perilesional skin to reduce itch, to characterize multidimensional sensations of itch in chronic wounds, to identify specific cytokine and chemokine expressions that are correlated to a tailored-based approach, and to develop practical guidelines.
Hidradenitis suppurativa (HS) is a chronic, burdensome inflammatory skin disorder mainly affecting adults with an infrequent onset during childhood or adolescence. Guidelines regarding the ...therapeutic drugs in pediatric HS patients are lacking. We describe the case of a 16-year-old girl affected by HS with a massive impact of the disease on her daily activities. She underwent antibiotics, estroprogestinics, isotretinoin, and drainage procedures with partial and short-term improvement. We treated the patient with adalimumab and assessed disease severity using BMI, pain VAS, Hurley, m-Sartorius, and HS-PGA. The treatment has been continued for 4 years with a strong improvement of clinical and psychological outcome. No side effects were recorded throughout the treatment period.
Severe liver disease markers assessed before HCV eradication are acknowledged to usually improve after the SVR. We prospectively evaluated, in the PITER cohort, the long-term HCC risk profile based ...on predictors monitored after HCV eradication by direct-acting antivirals in patients with cirrhosis.
HCC occurrence was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the post-treatment variables associated with de-novo HCC; their predictive power was presented in a nomogram.
After the end of therapy (median follow-up:28.47 months), among 2064 SVR patients, 119 (5.8%) developed de-novo HCC. The HCC incidence was 1.90%, 4.21%, 6.47% at 12-, 24- and 36-months from end-of-therapy, respectively (incidence rate 2.45/100 person-years). Age, genotype 3, diabetes, platelets (PLT)≤120,000/µl and albumin ≤3.5g/dl levels were identified as pre-treatment HCC independent predictors. Adjusting for age, the post-treatment PLT≤120,000/µl (AdjHR 1.92; 95%CI:1.06-3.45) and albumin≤3.5g/dl (AdjHR 4.38; 95%CI 2.48-7.75) values were independently associated with HCC occurrence. Two different risk profiles were identified by combining long-term post-therapy evaluation of PLT ≤ vs. >120,000/µl and albumin ≤ vs. >3.5g/dl showing a significant different HCC incidence rate of 1.35 vs. 3.77/100 p-y, respectively.
The nomogram score based on age, PLT and albumin levels after SVR showed an accurate prediction capability and may support the customizing management for early HCC detection.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Introduction
It is essential to use the correct injection technique (IT) to avoid skin complications such as lipohypertrophy (LH), local inflammation, bruising, and consequent repeated unexplained ...hypoglycemia episodes (hypos) as well as high HbA1c (glycated hemoglobin) levels, glycemic variability (GV), and insulin doses. Structured education plays a prominent role in injection technique improvement. The aim was to assess the ability of structured education to reduce (i) GV and hypos, (ii) HbA1c levels, (iii) insulin daily doses, and (iv) overall healthcare-related costs in outpatients with T2DM who were erroneously injecting insulin into LH.
Methods
318 patients aged 19–75 years who had been diagnosed with T2DM for at least 5 years, were being treated with insulin, were routinely followed by a private network of healthcare centers, and who had easily seen and palpable LH nodules were included in the study. At the beginning of the 6-month run-in period (T−6), all patients were trained to perform structured self-monitoring of blood glucose and to monitor symptomatic and severe hypos (SyHs and SeHs, respectively). After that (at T0), the patients were randomly and equally divided into an intervention group who received appropriate IT education (IG) and a control group (CG), and were followed up for six months (until T+6). Healthcare cost calculations (including resource utilization, loss of productivity, and more) were carried out based on the average NHS reimbursement price list.
Results
Baseline characteristics were the same for both groups. During follow-up, the intra-LH injection rate for the CG progressively decreased to 59.9% (
p
< 0.001), a much smaller decrease than seen for the IG (1.9%,
p
< 0.001). Only the IG presented significant decreases in HbA1c (8.2 ± 1.2% vs. 6.2 ± 0.9%;
p
< 0.01), GV (247 ± 61 mg/dl vs. 142 ± 31 mg/dl;
p
< 0.01), insulin requirement (− 20.7%,
p
< 0.001), and SeH and SyH prevalence (which dropped dramatically from 16.4 to 0.6% and from 83.7 to 7.6%, respectively;
p
< 0.001). In the IG group only, costs—including those due to the reduced insulin requirement—decreased significantly, especially those relating to SeHs and SyHs, which dropped to €25.8 and €602.5, respectively (
p
< 0.001).
Conclusion
Within a 6-month observation period, intensive structured education yielded consistently improved metabolic results and led to sharp decreases in the hypo rate and the insulin requirement. These improvements resulted in a parallel drop in overall healthcare costs, representing a tremendous economic advantage for the NHS. These positive results should encourage institutions to resolve the apparently intractable problem of LH by financially incentivizing healthcare teams to provide patients with intensive structured education on proper injection technique.
Trial Registration
Trial registration no. 118/15.04.2018, approved by the Scientific and Ethics Committee of Campania University “Luigi Vanvitelli,” Naples, Italy, and by the institutional review board (IRB Min. no. 9926 dated 05.05.2018).
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