Pneumococcal vaccination in adults: rationale, state of the art and perspectives

Streptococcus pneumoniae (SP) is a leading cause of morbid- ity and mortality worldwide. Despite the availability, since the early 1980s, of a 23-valent pneumococcal polysaccharide vaccine (PPV23), its recommendation and increased use in the last decades, and the indirect benefits against invasive pneumococcal diseases following the pediatric immunization strategies with the 7-valent pneumococcal conjugate vaccine (PCV7), pneumoccal diseases, particularly Community Acquired Pneumonia (CAP), still remain a substantial burden among older adults in Western countries. The recent availability on the market of a second generation of pneumococcal conjugate vaccines, with an enlarged spectrum ofprotection against some serotypes not included in the PCV7 (i.e., the 13-valent pneumococcal conjugate vaccine ? PCV13), opens new interesting perspectives for improving the control of this sig- nificant health-care issue among the entire population. The most interesting and up-dated epidemiological data regard- ing the impact of SP in adults and the elderly in Western countries, together with the available evidence concerning the efficacy and effectiveness of the PPV23 in the same population, are reported and discussed below. The full article is free available on www.jpmh.or

Low-dose oral imatinib in the treatment of systemic sclerosis interstitial lung disease unresponsive to cyclophosphamide: a phase II pilot study

Introduction: Pulmonary involvement represents a major cause of death of systemic sclerosis (SSc) patients. Recent data suggest that tyrosine kinase inhibitors, such as imatinib, may be a therapeutic option for SSc patients. However, preliminary published clinical trials were inconclusive about imatinib efficacy and showed side effects. The purpose of this study was to verify efficacy and tolerability of low-dose imatinib on interstitial lung disease in a cohort of SSc patients unresponsive to cyclophosphamide therapy.Methods: Thirty consecutive SSc patients with active pulmonary involvement, unresponsive to cyclophosphamide, were treated with imatinib 200 mg/day for 6 months followed by a 6-month follow-up. A "good response" was defined as an increase of forced vital capacity (FVC) by more of 15% and/or increase of diffusing capacity of carbon monoxide (DLCO) > 15% and PaO2 > 90% of initial value and high-resolution computed tomography (HRCT)-scan pattern unchanged or improved.Results: Twenty-six patients completed the study. Three patients died and one patient was lost to follow-up. Four patients (15.32%) had a good response, 7 worsened and 15 had a stabilized lung disease. Overall, 19 (73.07%) patients had an improved or stabilized lung disease. After a 6-month follow-up, 12 (54.5%) of the 22 patients showed an improved or stabilized lung disease.Conclusions: Lung function was stabilized in a large proportion of patients unresponsive to cyclophosphamide therapy and a beneficial outcome emerged from the analysis of HRCT lung scans. There was no significant improvement of skin involvement, and the low dose was well tolerated. These data provide useful suggestions to design future randomized clinical trials for SSc therapeutics

Update of EULAR recommendations for the treatment of systemic sclerosis

The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc

ANCA-associated vasculitis.

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are characterized by the development of autoantibodies to the neutrophil proteins leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic GPA (EGPA), are defined according to clinical features. However, genetic and other clinical findings suggest that these clinical syndromes may be better classified as PR3-positive AAV (PR3-AAV), MPO-positive AAV (MPO-AAV) and, for EGPA, by the presence or absence of ANCA (ANCA+ or ANCA-, respectively). Although any tissue can be involved in AAV, the upper and lower respiratory tract and kidneys are most commonly and severely affected. AAVs have a complex and unique pathogenesis, with evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation, recruitment and injury, with effector T cells also involved. Without therapy, prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. Meeting these challenges requires a more detailed knowledge of the fundamental biology of AAV as well as cooperative international research and clinical trials with meaningful input from patients

Dual Diagnosis and Application Problems in the Use of the Construct: A Review of Literature

Dual diagnosis (DD) commonly identifies a condition of co-occurrence of substance use disorders and psychological or psychiatric disorders. Many scholars have tried to explain this phenomenon, yet no agreement has been found: methodologies of intervention and treatment are numerous, but there is no uniformity of methodology. Our work aims to search critical aspects linked to this fragmented framework, to facilitate those who use the construct of DD. We have elaborated a literary review focused on specific critical contributions to the theoretical and methodological complexity of the construct. Scopus, PubMed, and Scholar were used as search engines. Our research reveals significant problems around several thematic areas: Defining, Operative and Treatment; Economic and Policy; Pharmacological Approach; and Patients' Perspectives Issues. Consistent issues are discussed with regard to DD: innovation should start from its limits. Future research should look for alternative theoretical formulations and consequent intervention experiences to provide new perspectives

The dangerous synergism between influenza and Streptococcus pneumoniae and innovative perspectives of vaccine prevention

Secondary bacterial pneumonia, particularly sustained by Streptococcus pneumoniae (Sp), represents an important cause of excess mortality during both influenza epidemics and pandemics. The lethal synergism between influenza virus and Sp was first suggested by studies performed on samples collected during autopsy from victims of 1918 influenza pandemic, and recently confirmed by data collected during the 2009 A/H1N1v influenza pandemic. Moreover, researches carried out in animal model contributed to partially clarify the pathogenic mechanisms underlying the synergism between these two etiological agents. Since 2000, a seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the US, and in the following year in Europe, determining substantial and almost immediate benefits in terms of reduction of invasive pneumococcal disease (IPD) in both vaccinated children and adults through induction of herd protection. Furthermore, several researches have recently demonstrated the capacity of the PCV7 to prevent community-acquired pneumonia (CAP) and, in particular, influenza-associated pneumonia hospitalisations among children. Taking into account the above-mentioned positive results obtained with PCV7, the availability of a new generation of conjugate pneumococcal vaccine with an enlarged antigenic spectrum (i.e. PCV13) offers promising perspectives, to improve the control of influenza through the protection offered against its major complications, particularly CAP, not only in children, but also among adults

Where are we going in the management of interstitial lung disease in patients with systemic sclerosis?

Interstitial lung disease (ILD) affects about 90% of patients with systemic sclerosis (SSc). It is associated with a restrictive lung disease in only 30% of patients and is progressive in an even lower percentage. A low forced vital capacity at presentation, an extent of lung fibrosis >20% as detected by lung high-resolution computed tomography, high serum interleukin-6 levels, anti-topoisomerase I antibody positivity and diffuse cutaneous SSc are each associated with SSc-ILD progression. However, no such association is absolute. Treating patients with a recent deterioration of lung function may allow to capture those with active disease. To date, cyclophosphamide (CYC) is the only drug found to stabilize or improve lung function in randomized clinical trials, but its small beneficial effect is short lived. Therefore, immunosuppressive maintenance therapy after CYC treatment is warranted. At present, however, the best therapeutical strategy after CYC therapy both in responders and in non-responders to CYC is still controversial. Based on a review of the literature, we suggest an approach to the management of SSc-ILD