Safety of Oral Paracetamol – Analysis of Data from a Spontaneous Reporting System in Poland

Purpose: To determine the safety of oral coated paracetamol tablets 500 mg and oral suspension 120 mg/5 mL produced by Hasco-Lek Poland.Methods: We analyzed sales volume and data obtained from the  monitoring of spontaneous reports on the adverse effects of paracetamol collected in the period between November 2000 and June 2012.Results: A total of 45,694 units of coated paracetamol tablets (500 mg) and 6,048,289 units of paracetamol oral suspension (120 mg/5 mL) were marketed during that period. There were 4 spontaneous reports of adverse effects.Conclusion: Oral paracetamol is a safe medication rarely causing adverse effects but it is possible that the existing spontaneous monitoring system for adverse effects in Poland is not sensitive enough to detect all adverse effects, and needs improvement.Keywords: Adverse reaction, NSAIDs, Pharmacovigillance,  Pharmoepidemiolog

Influenza vaccination in pregnancy — current data on safety and effectiveness

Pregnant women are at risk of severe and complicated influenza, and so are children aged 2-5 years. Despite numerous recommendations, influenza vaccination coverage in pregnant women is still low. The trigger for this article was the development of new quadrivalent influenza vaccines along with the publication of new studies on the safety and effectiveness of inactivated influenza vaccines in pregnant women, administered also in the first trimester of pregnancy. The inactivated quadrivalent influenza vaccine is a safe and effective measure for preventing influenza in both mother and child. Live attenuated influenza vaccines are contraindicated in pregnant women, whereas inactivated influenza vaccines should be recommended to all pregnant women, either healthy or with comorbidities. Influenza vaccines can be administered during any pregnancy trimester, at least two weeks before delivery. The time of vaccination depends on vaccine availability; however, it should not be postponed unless there are significant medical contraindications

Pertussis vaccination in pregnancy — current data on safety and effectiveness

Whooping cough/pertussis is a respiratory infection caused by the bacteria Bordetella pertussis and Bordetella parapertussis. The World Health Organization (WHO) has identified whooping cough as one of the least controlled diseases in all age groups. Clinically, the catarrhal phase manifests itself as flu-like, nonspecific symptoms: cough, runny nose, mild fever, which, regrettably, makes early diagnosis difficult. The severe course is more specific (an audible inspiratory whoop followed by paroxysmal cough and vomiting). Currently, in Poland the highest percentage of cases is observed in children aged 0–4 years, followed by children over 15 years of age, with peaks among teens and seniors. Notably, hospitalization, morbidity and mortality rates are considerable in children (especially infants). Vaccinating pregnant women against pertussis provides approximately 90% protection to infants in their first two months of life. It is an effective form of preventing pertussis in infants. Moreover, it is safe for pregnant women and their children. The Advisory Committee on Immunization Practices (ACIP) recommends Tdap vaccination to every pregnant woman between 27–36 weeks of pregnancy

T-Cell Exhaustion in HIV-1/Hepatitis C Virus Coinfection Is Reduced After Successful Treatment of Chronic Hepatitis C.

BACKGROUND T-cell responses during chronic viral infections become exhausted, which is reflected by upregulation of inhibitory receptors (iRs) and increased interleukin 10 (IL-10). We assessed 2 iRs-PD-1 (programmed cell death protein 1) and Tim-3 (T-cell immunoglobulin and mucin domain-containing protein 3)-and IL-10 mRNAs in peripheral blood mononuclear cells (PBMCs) and their soluble analogs (sPD-1, sTim-3, and IL-10) in plasma in chronic HIV-1/hepatitis C virus (HCV) coinfection and explored the effect of HCV treatment on these markers. We also aimed to establish whether iR expression may be determined by the HCV CD8+ T-cell immunodominant epitope sequence. METHODS Plasma and PBMCs from 31 persons with chronic HIV-1/HCV coinfection from the Swiss HIV Cohort Study were collected before and after HCV treatment. As controls, 45 persons who were HIV-1 negative with chronic HCV infection were recruited. Exhaustion markers were assessed by enzyme-linked immunosorbent assay in plasma and by quantitative reverse transcription polymerase chain reaction in PBMCs. Analysis of an HCV epitope sequence was conducted by next-generation sequencing: HLA-A*02-restricted NS31073-1081 and NS31406-1415 and HLA-A*01-restricted NS31436-1444. RESULTS The study revealed higher plasma sPD-1 (P = .0235) and IL-10 (P = .002) levels and higher IL-10 mRNA in PBMCs (P = .0149) in HIV-1/HCV coinfection. A decrease in plasma sPD-1 (P = .0006), sTim-3 (P = .0136), and IL-10 (P = .0003) and Tim-3 mRNA in PBMCs (P = .0210) was observed following successful HCV treatment. Infection with the HLA-A*01-restricted NS31436-1444 ATDALMTGY prototype variant was related to higher sTim-3 levels than infection with the ATDALMTGF escape variant (P = .0326). CONCLUSIONS The results underscore the synergistic effect of coinfection on expression of exhaustion markers, their reduction following successful HCV treatment and imply that iR levels may operate on an epitope-specific manner

T-Cell Exhaustion in HIV-1/Hepatitis C Virus Coinfection Is Reduced After Successful Treatment of Chronic Hepatitis C

BACKGROUND T-cell responses during chronic viral infections become exhausted, which is reflected by upregulation of inhibitory receptors (iRs) and increased interleukin 10 (IL-10). We assessed 2 iRs-PD-1 (programmed cell death protein 1) and Tim-3 (T-cell immunoglobulin and mucin domain-containing protein 3)-and IL-10 mRNAs in peripheral blood mononuclear cells (PBMCs) and their soluble analogs (sPD-1, sTim-3, and IL-10) in plasma in chronic HIV-1/hepatitis C virus (HCV) coinfection and explored the effect of HCV treatment on these markers. We also aimed to establish whether iR expression may be determined by the HCV CD8$^{+}$ T-cell immunodominant epitope sequence. METHODS Plasma and PBMCs from 31 persons with chronic HIV-1/HCV coinfection from the Swiss HIV Cohort Study were collected before and after HCV treatment. As controls, 45 persons who were HIV-1 negative with chronic HCV infection were recruited. Exhaustion markers were assessed by enzyme-linked immunosorbent assay in plasma and by quantitative reverse transcription polymerase chain reaction in PBMCs. Analysis of an HCV epitope sequence was conducted by next-generation sequencing: HLA-A*02-restricted NS3$_{1073-1081}$ and NS3$_{1406-1415}$ and HLA-A*01-restricted NS3$_{1436-1444}$. RESULTS The study revealed higher plasma sPD-1 (P = .0235) and IL-10 (P = .002) levels and higher IL-10 mRNA in PBMCs (P = .0149) in HIV-1/HCV coinfection. A decrease in plasma sPD-1 (P = .0006), sTim-3 (P = .0136), and IL-10 (P = .0003) and Tim-3 mRNA in PBMCs (P = .0210) was observed following successful HCV treatment. Infection with the HLA-A*01-restricted NS3$_{1436-1444}$ ATDALMTGY prototype variant was related to higher sTim-3 levels than infection with the ATDALMTGF escape variant (P = .0326). CONCLUSIONS The results underscore the synergistic effect of coinfection on expression of exhaustion markers, their reduction following successful HCV treatment and imply that iR levels may operate on an epitope-specific manner

Medial Prefrontal and Anterior Insular Connectivity in Early Schizophrenia and Major Depressive Disorder: A Resting Functional MRI Evaluation of Large-Scale Brain Network Models

Anomalies in the medial prefrontal cortex, anterior insulae, and large-scale brain networks associated with them have been proposed to underlie the pathophysiology of schizophrenia and major depressive disorder (MDD). In this study, we examined the connectivity of the medial prefrontal cortices and anterior insulae in 24 healthy controls, 24 patients with schizophrenia, and 24 patients with MDD early in illness with seed based resting state functional magnetic resonance imaging analysis using Statistical Probability Mapping. As hypothesized, reduced connectivity was found between the medial prefrontal cortex and the dorsal anterior cingulate cortex and other nodes associated with directed effort in patients with schizophrenia compared to controls while patients with MDD had reduced connectivity between the medial prefrontal cortex and ventral prefrontal emotional encoding regions compared to controls. Reduced connectivity was found between the anterior insulae and the medial prefrontal cortex in schizophrenia compared to controls, but contrary to some models emotion processing regions failed to demonstrate increased connectivity with the medial prefrontal cortex in MDD compared to controls. Although, not statistically significant after correction for multiple comparisons, patients with schizophrenia tended to demonstrate decreased connectivity between basal ganglia-thalamocortical regions and the medial prefrontal cortex compared to patients with MDD, which might be expected as these regions effect action. Results were interpreted to support anomalies in nodes associated with directed effort in schizophrenia and nodes associated with emotional encoding network in MDD compared to healthy controls

Rfam: Wikipedia, clans and the “decimal” release

The Rfam database aims to catalogue non-coding RNAs through the use of sequence alignments and statistical profile models known as covariance models. In this contribution, we discuss the pros and cons of using the online encyclopedia, Wikipedia, as a source of community‐derived annotation. We discuss the addition of groupings of related RNA families into clans and new developments to the website. Rfam is available on the Web at http://rfam.sanger.ac.uk

The European 2015 drought from a hydrological perspective

In 2015 large parts of Europe were affected by drought. In this paper, we analyze the hydrological footprint (dynamic development over space and time) of the drought of 2015 in terms of both severity (magnitude) and spatial extent and compare it to the extreme drought of 2003. Analyses are based on a range of low flow and hydrological drought indices derived for about 800 streamflow records across Europe, collected in a community effort based on a common protocol. We compare the hydrological footprints of both events with the meteorological footprints, in order to learn from similarities and differences of both perspectives and to draw conclusions for drought management. The region affected by hydrological drought in 2015 differed somewhat from the drought of 2003, with its center located more towards eastern Europe. In terms of low flow magnitude, a region surrounding the Czech Republic was the most affected, with summer low flows that exhibited return intervals of 100 years and more. In terms of deficit volumes, the geographical center of the event was in southern Germany, where the drought lasted a particularly long time. A detailed spatial and temporal assessment of the 2015 event showed that the particular behavior in these regions was partly a result of diverging wetness preconditions in the studied catchments. Extreme droughts emerged where preconditions were particularly dry. In regions with wet preconditions, low flow events developed later and tended to be less severe. For both the 2003 and 2015 events, the onset of the hydrological drought was well correlated with the lowest flow recorded during the event (low flow magnitude), pointing towards a potential for early warning of the severity of streamflow drought. Time series of monthly drought indices (both streamflow- and climate-based indices) showed that meteorological and hydrological events developed differently in space and time, both in terms of extent and severity (magnitude). These results emphasize that drought is a hazard which leaves different footprints on the various components of the water cycle at different spatial and temporal scales. The difference in the dynamic development of meteorological and hydrological drought also implies that impacts on various water-use sectors and river ecology cannot be informed by climate indices alone. Thus, an assessment of drought impacts on water resources requires hydrological data in addition to drought indices based solely on climate data. The transboundary scale of the event also suggests that additional efforts need to be undertaken to make timely pan-European hydrological assessments more operational in the future