Real-Life Impact of Drug Toxicity on Dolutegravir Tolerability: Clinical Practice Data from a Multicenter Italian Cohort

Dolutegravir (DTG) is currently one of the most used Integrase inhibitors (INI) in antiretroviral therapies (ARV) in both naïve and experienced people living with HIV (PLWHIV). We analyzed a multicenter cohort of PLWHIV, both naïve and experienced, starting an ARV including DTG. We enrolled 3775 PLWHIV: 2763 (73.2%) were males, with a median age of 50 years. During 9890.7 PYFU, we observed 930 discontinuations (9.4 per 100 PYFU). Estimated probabilities of maintaining DTG at three and five years were 75.1% and 67.2%, respectively. Treatment-naïve pts showed a lower probability of maintaining DTG at three and five years compared to treatment-experienced PLWHIV (log-rank p < 0.001). At a multivariate analysis, a longer time of virological suppression (aHR 0.994, p < 0.001) and having experienced a previous virological failure (aHR 0.788, p = 0.016) resulted protective against DTG discontinuation. Most discontinuations (84.0%) happened within the first 12 months of DTG initiation, in particular, 92.2% of discontinuations due to neuropsychiatric toxicity were observed in the first year. Our data confirm the overall good tolerability of DTG in clinical practice, with a low rate of discontinuations. CNS toxicity resulted the main reason for DTG discontinuation, with most related interruptions happening in the first year from DTG introduction.     

Interventions on Microbiota: Where Do We Stand on a Gut–Brain Link in Autism? A Systematic Review

The alteration of the microbiota–gut–brain axis has been recently recognized as a critical modulator of neuropsychiatric health and a possible factor in the etiopathogenesis of autism spectrum disorders (ASD). This systematic review offers practitioners an overview of the potential therapeutic options to modify dysbiosis, GI symptoms, and ASD severity by modulating the microbiota–gut–brain axis in ASD, taking into consideration limits and benefits from current findings. Comprehensive searches of PubMed, Scopus, the Web of Science Core Collection, and EMBASE were performed from 2000 to 2021, crossing terms referred to ASD and treatments acting on the microbiota–gut–brain axis. A total of 1769 publications were identified, of which 19 articles met the inclusion criteria. Data were extracted independently by two reviewers using a preconstructed form. Despite the encouraging findings, considering the variability of the treatments, the samples size, the duration of treatment, and the tools used to evaluate the outcome of the examined trials, these results are still partial. They do not allow to establish a conclusive beneficial effect of probiotics and other interventions on the symptoms of ASD. In particular, the optimal species, subspecies, and dosages have yet to be identified. Considering the heterogeneity of ASD, double-blind, randomized, controlled trials and treatment tailored to ASD characteristics and host-microbiota are recommended.     

Are there gender-specific differences in pregnancy outcome and placental abnormalities of pregnancies complicated with small for gestational age?

Archives of Gynecology and Obstetrics - Adaptations to pathological intrauterine environment might differ in relation to fetal gender. We aimed to study sex-specific differences in placental...     

The Italian multicenter experience with edaravone in amyotrophic lateral sclerosis

Journal of Neurology - The aim of the study is to analyze the ALS disease progression and respiratory function of Italian patients treated with edaravone (EVN), as well as the adherence to, and the...     

Serum phosphorylated neurofilament heavy-chain levels reflect phenotypic heterogeneity and are an independent predictor of survival in motor neuron disease

Journal of Neurology - To investigate the prognostic role and the major determinants of serum phosphorylated neurofilament heavy -chain (pNfH) concentration across a large cohort of motor neuron...     

Cardiac resynchronization therapy: variations in echo-guided optimized atrioventricular and interventricular delays during follow-up

BACKGROUND: Relatively few data are available on long-term echocardiographic optimization of atrioventricular (AV) and interventricular (VV) delay programming in cardiac resynchronization therapy (CRT). We assessed variations in optimized AV and VV delays during long-term follow-up. METHODS: Thirty-seven consecutive heart failure patients received Doppler echocardiographic optimization of AV and VV delay within 48 hours from CRT device implantation, at 6 months and at 12 months (the last for the first enrolled 14 patients). RESULTS: After implantation, median optimized AV delay was 100 ms (range, 45 ms); VV optimization led to simultaneous biventricular activation in 4 patients, left ventricular preactivation in 17 patients and right ventricular preactivation in 16 patients. At 12 months median AV delay decreased to 85 ms (23 ms) (P < 0.05 vs. baseline). With respect to previous assessment, VV delay variations > or =40 ms were observed in 41% of the patients at 6 months and in 57% of the tested patients at 12 months. A nonconcordance (by Kappa test) of optimized VV delays was found between each new assessment and the previous one. VV delay optimization was associated with significant (P < 0.001) increases in aortic velocity time integral both at baseline and during follow-up. CONCLUSIONS: Echocardiographic optimization of AV and VV delay is associated with broad intraindividual variability during follow-up. A new assessment of optimized VV delays during long-term follow-up reveals a nonconcordance with previous values and provides increases in forward stroke volume.     

Comparison of atorvastatin versus fenofibrate in reaching lipid targets and influencing biomarkers of endothelial damage in patients with familial combined hyperlipidemia

Statins and fibrates have different effects on lipid abnormalities of familial combined hyperlipidemia (FCHL); thus, the selection of the first-line drug is troublesome. We evaluated to what extent monotherapy with a potent statin is more effective than fibrate in reaching the recommended lipid targets in FCHL. Fifty-six patients were randomized to receive optimal dosage of atorvastatin (n = 27) or 200 mg/d micronized fenofibrate (n = 29) for 24 weeks. To reach the optimal dosage, atorvastatin was up-titrated at each follow-up visit if low-density lipoprotein (LDL) cholesterol >130 mg/dL (>100 mg/dL in patients with coronary or cerebrovascular disease). The effects of fenofibrate and atorvastatin on lipoprotein fractions as well as on plasma levels of endothelin-1 (ET-1) and adrenomedullin (AM) were also evaluated. At end of trial, a greater proportion of patients on atorvastatin (average dosage, 20.8 mg/d) reached lipid targets in comparison with those on fenofibrate (64% vs 32.1%, P = .02). Atorvastatin was significantly more effective in reducing total cholesterol, LDL cholesterol, apolipoprotein B, and non-high-density lipoprotein (HDL) cholesterol. Conversely, triglycerides decreased and HDL increased more during fenofibrate. Nevertheless, atorvastatin produced a marked reduction in very low-density lipoprotein and very low-density lipoprotein remnants. Atorvastatin lowered all LDL subtypes, although fenofibrate appeared to be more effective on denser LDL. Compared with 43 normolipemic controls, FCHL patients presented increased baseline plasma levels of ET-1 (P = .007) but not of AM. Fenofibrate, but not atorvastatin, significantly lowered ET-1 levels by 16.7% (P < .05). Neither drug significantly affected plasma concentrations of AM. In summary, although fenofibrate showed superiority in raising HDL and reducing ET-1, atorvastatin was more effective in reaching lipid targets in FCHL so that it can be proposed as the first-line option in the management of this atherogenic hyperlipidemia.     

Use of human fibrinogen and human thrombin for urethral reconstructive surgery

The objective of the present study is to test the use of a haemostatic sponge for urethral reconstructive surgery and to assess the relevant benefits. METHODS. The haemostatic sponge is made up of collagen with human fibrinogen and human thrombin. When the sponge gets in contact with fluids, such as blood, lymph or saline solution, the fibrinogen and thrombin are activated and form a fibrin net able to achieve local haemostasis and tissue regeneration. This kind of product was used in 30 selected patients (pts.), aged 19 - 70 (mean age: 35), who underwent single-stage anastomotic urethroplasty from January 2006 to March 2007: 22 bulbar end-to-end anastomoses and 8 bulbo- prostatic anastomoses. All operations were performed due to post-traumatic stricture of bulbar and posterior urethra. The main selection criterion for the use of the haemostatic sponge has always been the tendency to and/or the presence of bleeding in the different surgical stages. The sponge imbibed in saline solution and suitably modeled for all specific requirements was differently placed: sleeve-shaped in the case of bulbar anastomoses (16 pts.); as a "patch" in the centre of spongioplasty in bulbo-prostatic anastomoses (8 pts.), and within the widening incisions of the urethral roof performed between the two cavernous bodies at level of the intercrural septum (5 pts.). In 1 case (obese patient) a single sponge was placed after the deep perineal reconstruction on the bulbo-cavernous muscle- subcutaneous layers because of massive bleeding. RESULTS. In all cases a perfect control of haemostasis could be achieved, with immediate end of bleeding in the points where the haemostatic sponges were used. The dressings performed on day 3 upon removal of the compressive scrotum-perineal bandages did not show any late post-operative bleeding. The follow-up visits at month 1 and 3 yielded positive outcomes for all 30 patients, who achieved complete wound healing by first intention, and a perfect anastomosis especially in the bulbar end-to-end urethroplasty, confirmed by urethrografy at one month. CONCLUSIONS. The association of human fibrinogen and human thrombin in haemostatic sponges represents a manageable, useful product, apparently sure, not negatively interfering in repairing and regenerating tissue processes, and allowing a simple and direct control of important bleeding events occurring during urethral reconstructive surgery as well as other operations. It is therefore advisable to more widely use the product after a suitable followup period.     

A systematic review on the validity and reliability of an emergency department triage scale,the Manchester Triage System

Objective

To conduct a systematic review to check the level of validity and reliability of the Manchester Triage System and the quality of reporting of literature on this topic.

Design

This is a systematic review based on the PRISMA guideline on reporting systematic reviews.

Data sources

The systematic search of the international literature published from 1997 through 30 November 2012 in the PubMed, Embase, Cochrane Library, Cinahl, Web of Knowledge, and Scopus databases.

Review methods

This review included quantitative and qualitative research investigating the reliability and validity of the Manchester Triage System for the broad population of adults and children visiting the emergency department.After a systematic selection process, included studies were assessed on their quality by three researchers using the STARD guidelines.

Results

Twelve studies were included in the review. The studies investigated the inter- and intra-rater reliability using the “kappa” statistic; the validity was tested with many measures: validity in predicting mortality, hospital admission, under- and overtriage, used resources, and length of stay in the emergency department, as well as a reference standard rating.

Conclusions

In this review, the Manchester Triage System shows a wide inter-rater agreement range with a prevalence of good and very good agreement. Its safety was low because of the high rate of undertriage and the low sensitivity in predicting higher urgency levels. The high rate of overtriage could cause unnecessarily high use of resources in the emergency department. The quality of the reporting in studies of the reliability and validity of the Manchester Triage System is good.