Ribavirin Impairs Salivary gland function During Combination Treatment With Pegylated Interferon Alfa-2a In HEpatitis C patients

Background

Xerostomia is a common adverse event of unknown etiology observed during pegylated interferon (PegIFN)/Ribavirin (Rbv) treatment.

Objectives

To assess the frequency and mechanisms of xerostomia during PegIFN/Rbv therapy.

Patients and Methods

Thirty-one naïve patients with chronic hepatitis C consecutively received PegIFN-α2a (180 μg/week) plus Rbv (800–1200 mg/day). The controls were 10 patients with chronic hepatitis B who received PegIFN-α2a (180 μg/week). During treatment and follow-up, all patients underwent basal and masticatory stimulated sialometry,otorhinolaryngoiatric (ORL) examination, and a questionnaire survey to subjectively assess symptoms of oral dryness.

Results

Twenty-seven patients on PegIFN/Rbv and 4 on PegIFN (87% vs. 40%, P = 0.006) reported xerostomia. Thirty patients on PegIFN/Rbv combination therapy and 2 patients on monotherapy had ORL signs of salivary gland hypofunction (97% vs. 20%, P < 0.0001).Mean basal (A) and stimulated (B) salivary flow rates (mL/min) progressively decreased during PegIFN/Rbv treatment (A, 0.49 at baseline vs. 0.17 at the end of treatment, P < 0.0001; B, 1.24 at baseline vs. 0.53 at the end of treatment, P = 0.0004). At week 24 following PegIFN/Rbv treatment, salivary flow rates were similar to baseline (A, 0.53 at the end of follow-up vs. 0.49 at baseline; B, 1.19 at the end of follow-up vs. 1.24 at baseline). Salivary function was unaffected in monotherapy patients.

Conclusions

Rbv causes salivary gland hypofunction in hepatitis C patients receiving PegIFN/Rbv therapy, which promptly reverts to normal upon cessation of treatment.     

Suicide in a large population of former psychiatric inpatients

Aims: The aim of this study was to identify predictors of completed suicide in a wide sample of psychiatric inpatients receiving retrospective and prospective DSM‐IV diagnoses. Methods: We followed up 4441 severe psychiatric patients who were hospitalized for some time during a 35‐year period in a private hospital setting. We collected sociodemographic, clinical and temperamental data. Results: Ninety‐six patients from the sample committed suicide. There were no sex differences in suicide completion and no differences between major psychiatric disorders, but people who had been hospitalized for anxiety disorders did not commit suicide and people with bipolar disorders were more likely to commit suicide than people with unipolar major depression. Shorter‐term treatment with lithium and anticonvulsants, longer‐term treatment with antidepressants, history of suicide attempts, suicidal thinking, and single status positively predicted completed suicide. Suicide tended to occur after a mean period of about 14 years of duration of disease. Patients' symptoms during the period preceding suicide were assessed through interviewing patients' physicians or family members. Symptoms occurring in >10% of cases were, in decreasing order, inner tension, racing/crowded thoughts, aggressive behavior, guilt, psychomotor agitation, persecutory ideation, anxiety, and hallucinations. Surprisingly, cyclothymic temperament was less associated with completed suicide as compared to other temperaments. Conclusions: Suicide is likely to occur in a milieu of agitation, mixed anxiety and depression, and psychosis. Longer‐term mood stabilizer treatment may reduce the rate of completed suicide.     

Murder-suicide in the province of Milan, Italy: criminological analysis of cases 1990-2009

Murder-suicide is a relatively rare event, and familicide is rarer still. However, it is certainly not unknown, and has been described in the scientific literature from both a socio-criminological and pathological-forensic perspective since the last century. In a civilized urban area such as Milan and province, where there is a general reduction in the homicide rate, homicide-suicide occurs almost exclusively within the family, and has specific features that differentiate it from other types of homicide, whether connected with general criminality or organized crime. This article analyses the quantitative and qualitative features of cases of homicide-suicide occurring in Milan and province between 1990 and 2009 (20 years), considering temporal aspects and the development of the events, the weapons used, and the epidemiological and psychopathological features of the perpetrators and their victims.     

Two novel mutations in PEO1 (twinkle) gene associated with chronic external ophthalmoplegia

Maintenance and replication of mitochondrial DNA require the concerted action of several factors encoded by nuclear genome. The mitochondrial helicase Twinkle is a key player of replisome machinery. Heterozygous mutations in its coding gene, PEO1, are associated with progressive external ophthalmoplegia (PEO) characterised by ptosis and ophthalmoparesis, with cytochrome c oxidase (COX)-deficient fibres, ragged-red fibres (RRF) and multiple mtDNA deletions in muscle. Here we describe clinical, histological and molecular features of two patients presenting with mitochondrial myopathy associated with PEO. PEO1 sequencing disclosed two novel mutations in exons 1 and 4 of the gene, respectively. Although mutations in PEO1 exon 1 have already been described, this is the first report of mutation occurring in exon 4.     

Precision medicine in primary biliary cholangitis

For many years the one‐size‐fits‐all approach has been the only one available to manage patients affected by primary biliary cholangitis. The introduction of obeticholic acid in 2016 as a second‐line treatment, together with the creation and validation of several biochemically based scores to stratify the risk of progressive disease, has opened up the need to redefine clinical practice by changing the actual paradigm. The precision medicine initiative is a model of patient‐centered health care that aims to improve medicine based on genotypic and molecular characteristics that correlate to specific phenotypic, individual characteristics. In summary, the aim of the precision medicine is to define the right treatment for the right person at the right time. The availability of a second‐line disease‐modifying drug and new molecules in phase 2 or 3 trials makes this an exciting time for the precision medicine initiative in primary biliary cholangitis. In this review we describe the current risk stratification tools and we track a possible path towards the application of precision medicine in clinical daily life.