Meningococcal Quadrivalent (Serogroups A, C,W135, and Y) Conjugate Vaccine (Menveo®)

Menveo® is a quadrivalent meningococcal polysaccharide conjugate vaccine containing the four Neisseria meningitidis capsular polysaccharides, A, C, W135, and Y, each conjugated to the mutant diphtheria toxin, known as crossreactive material 197 (CRM₁₉₇). Administration of a single dose of the Menveo® vaccine elicited a strong immune response against all four vaccine serogroups in adolescents and adults in randomized, single- or multicenter, phase II or III trials. In adolescents, Menveo® was generally more immunogenic against vaccine serogroups than the polysaccharide conjugate vaccine Menactra® or the unconjugated polysaccharide vaccine Menomune®, in terms of seroresponse and/or seroprotection rates and geometric mean titers (GMTs) 1 month post-vaccination in two phase II or III studies. In two phase III trials in adults aged 19–55 years, the immunogenicity of Menveo® was generally noninferior or superior to that of Menactra® against all four vaccine serogroups, with regard to seroresponse/seroprotection rates, and GMTs 1 month after vaccination. Moreover, an exploratory arm of one of these studies suggested Menveo® was at least as immunogenic as Menomune® in adults aged 56–65 years. Longer term, the immunogenicity of Menveo® persisted for 12–22 months post-vaccination in the adolescent studies, with the vaccine generally remaining at least as immunogenic as Menactra® or Menomune®. Coadministration of Menveo® with a combined tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine or Tdap and human papillomavirus vaccines generally did not affect the immunogenicity of these vaccines in adolescents and young adults in two additional randomized, single- or multicenter, phase III studies. The tolerability profile of Menveo® was generally similar to that of the comparator vaccines Menactra® or Menomune® in adults and adolescents, and few Menveo® recipients experienced serious adverse events within 30 days or 6 months post-vaccination.     

A/H5N1 Prepandemic Influenza Vaccine (Vepacel®): A Guide to Its Use

Vepacel® is a prepandemic influenza vaccine (whole virion, Vero cell-derived, inactivated) containing antigen of H5N1 strain A/Vietnam/1203/2004 and is approved for use in the EU. Clinical immunogenicity studies with the vaccine have demonstrated good functional neutralizing antibody responses against the vaccine strain (A/Vietnam/1203/2004), and cross-reactivity against H5N1 strains from other clades. In general, adverse events observed in clinical immunogenicity studies with a whole virions H5N1 vaccine (A/Vietnam/1203/2004) were similar to those reported with non-adjuvanted, inactivated, split virion seasonal influenza vaccines.     

Octocog Alfa (Advate®): A Guide to Its Use in Hemophilia A

Prophylaxis or on-demand therapy with octocog alfa, antihemophilic factor, plasma/albumin-free method (Advate(?)) is effective for the prevention and treatment of bleeding episodes and for perioperative management in pediatric and adult patients with hemophilia A. Routine prophylaxis with Advate(?) also prevents bleeding episodes in patients with hemophilia A; moreover, routine prophylaxis with Advate(?) is more effective in preventing bleeding episodes than on-demand therapy. Advate(?) is generally well tolerated in patients with hemophilia A. Serious adverse events with Advate(?) therapy include the development of high-titer factor VIII inhibitors (usually in previously untreated patients) and hypersensitivity reactions. There are no comparative trials of Advate(?) and other factor VIII concentrates. Nevertheless, current evidence indicates that Advate(?) is an effective option for the management of pediatric and adult patients with hemophilia A.     

Shingles (Herpes Zoster) Vaccine (Zostavax<Superscript>®</Superscript>): A Review in the Prevention of Herpes Zoster and Postherpetic Neuralgia

Zostavax^® is a live attenuated shingles (herpes zoster) vaccine approved in the EU for the prevention of herpes zoster (HZ) and postherpetic neuralgia (PHN) in adults aged ≥50 years. Zoster vaccine protected against HZ in adults aged 50–59 years (ZEST trial) and ≥60 years [Shingles Prevention Study (SPS)], and also reduced the burden of illness associated with HZ and the risk of PHN in adults aged ≥60 years (SPS). A large amount of real-world data also supports the efficacy of zoster vaccine. Results of the SPS Short- and Long-Term Persistence Substudies and real-world studies indicate that zoster vaccine provided continued benefit in the longer term, albeit with a gradual decline in vaccine efficacy over time; long-term effectiveness studies are ongoing. The need for a booster dose is still unknown, but a study showed that, if necessary, a booster dose administered to adults aged ≥70 years who received their first dose of zoster vaccine ≥10 years previously was immunogenic. Zoster vaccine had a favourable safety and tolerability profile, with the most commonly reported adverse events being non-severe injection-site reactions. In conclusion, zoster vaccine reduces the incidence of HZ and PHN, thereby reducing the burden of illness associated with HZ; improved uptake of zoster vaccine is needed.     

Co–circulation of different genotype,sub-genotype and serotypes of hepatitis B virus (HBV) and its epidemiology in Assam: A north-eastern state of India

PurposeHepatitis B virus (HBV) infection is a global health problem. HBV has different genotypes and subgenotypes with geographical distinctiveness. Aims: To study the molecular epidemiology and distribution pattern of HBV in Assam; a distinct state of India that may have different genotypic divergence. Settings and design: Patients attending a tertiary care hospital susceptive of Hepatitis B were included, irrespective of age and sex in different agro-climatic zones of Assam.MethodsSamples positive for Hepatitis B surface antigen test and COBAS®TaqMan® HBV tests were further confirmed by PCR and sequencing followed by phylogenetic analysis.Statistical analysis used: Chi-square test was used to determine whether there was a significant difference among the results in this study.Results: An increase trend of HBV positive cases has been observed in the state. The incidence in female was lower than that of male and age group 26–35 years was most vulnerable. Genotype D, subgenotype D2 and serotype ayw3 were predominant genotype, subgenotype and serotype. The prevalence of subgenotype C3 was a new finding. Phylogenetic analysis showed that the genotypes of HBV prevailing in the state have close relationship with neighboring countries of India which may be due to increased cross border migration of populationConclusionsThis comprehensive study of HBV in Assam described the distribution of HBV genotypes and subgenotypes and serotypes in different agro-climatic zones of Assam. These findings will help to formulate the roadmap for prevention and control of the disease as well as targeted therapy of HBV in this State.     

Comparison of Immune Responses Induced in Mice by Vaccination with DNA Vaccine Constructs Expressing Mycobacterial Antigen 85A and Interleukin-21 and Bacillus Galmette-Guérin

In this paper, we addressed the immune adjuvant effects of interleukin(IL)-21 on DNA vaccine constructs expressing mycobacterium tuberculosis (TB) Ag85A and compared immune responses induced in mice inoculated DNA vaccine constructs expressing Ag85A and IL-21 with mice inoculated DNA vaccine constructs expressing Ag85A alone or Bacillus Galmette-Guérin(BCG.). In this experiment, the gene of IL-21 was firstly amplified from plasmid pcDNA3.1-mIL21 by PCR and cloned into the plasmid pRSC, forming recombinant plasmid pRSC-IL21. Then, the gene of Ag85A was amplified from the plasmid pIRES-Ag85A by PCR and cloned into the recombinant pRSC-IL21 again, finally forming co-expression DNA vaccine constructs pRSC-IL21-Ag85A. It was identified by the analysis of endonuclease digestion, DNA sequencing, the IL-21 and Ag85A expression in SP2/0 cells. Mice were i.m. immunized with BCG, DNA vaccine constructs pRSC-Ag85A or pRSC-IL21-Ag85A respectively, and the immune responses induced in mice was compared with other vaccines. The results showed that the DNA vaccine constructs pRSC-IL21-Ag85A was successfully constructed since the Ag85A and IL-21 was correctly expressed in SP2/0 cells respectively, and it elicited stronger immune responses in Balb/c mice than that of mice immunized with pRSC-Ag85A and the efficiency was as BCG did. We concluded that the IL-21 was a promising immune adjunctive modality to enhance immunigenicity of DNA vaccine containing Ag85A and the study provided the possibility of further development of immune accessory effect of IL-21 on DNA vaccine against TB.     

The Growing Use of Virtual Reality in Cognitive Rehabilitation: Fact,Fake or Vision? A Scoping Review

ObjectiveThis review aims to evaluate the role of Virtual Reality (VR) in cognitive rehabilitation of different neurological diseases, and the accessibility to healthcare systems providing this type of treatment.Method of ResearchStudies performed between 2003 and 2017 and fulfilling the selected criteria were found on PubMed, Scopus, Cochrane and Web of Sciences databases. The search combined the terms VR rehabilitation with different neurological disease.ResultsOur findings showed that neurological patients performed significant improvement in many cognitive domains (executive and visual-spatial abilities; speech, attention and memory skills) following the use of VR training.ConclusionsThis review supports the idea that rehabilitation through new VR tools could positively affect neurological patients’ outcomes, by boosting motivation and participation so to get a better response to treatment. In particular, VR can be used to enhance the effects of conventional therapies, promoting longer training sessions and a reduction in overall hospitalization time.     

BAY 81-8973 (Octocog Alfa; Kovaltry<Superscript>®</Superscript>): A Review in Haemophilia A

BAY 81-8973 (octocog alfa; Kovaltry^®) is an unmodified, full-length, recombinant factor VIII (FVIII) concentrate with the same amino acid sequence as Kogenate^® FS, but produced with innovative manufacturing technologies. This narrative review discusses the clinical efficacy and tolerability of BAY 81-8973 in haemophilia A, as well as summarizing its pharmacological properties. Results of the LEOPOLD I, LEOPOLD II and LEOPOLD Kids trials demonstrated that routine prophylaxis with intravenous BAY 81-8973 was associated with a low annualized bleeding rate (ABR) in previously treated adult and paediatric patients with severe haemophilia A. In terms of the ABR, BAY 81-8973 prophylaxis was more effective than on-demand treatment. Intravenous BAY 81-8973 was generally well tolerated, with no inhibitor development reported in previously treated patients in the completed LEOPOLD trial programme. In conclusion, BAY 81-8973 is a useful option for prophylaxis and treatment in adult and paediatric patients with haemophilia A.     

Use of Deep Neural Networks in the Detection and Automated Classification of Lesions Using Clinical Images in Ophthalmology,Dermatology, and Oral Medicine—A Systematic Review

Journal of Digital Imaging - Artificial neural networks (ANN) are artificial intelligence (AI) techniques used in the automated recognition and classification of pathological changes from clinical...     

Effects of a neem seed extract (MiteStop®) on mallophages (featherlings) of chicken: in vivo and in vitro studies

Mallophages of birds (featherlings) are mostly very tiny and can even as adults better be recognized by their movements than by their elongate body shape when using just the naked eye. Since some species (e.g., the “shaft louse” Menopon gallinae, the elongate feather louse Lipeurus caponis, or Columbicola sp.) may pierce the pulp of feathers or the skin by their biting or scratching mandibles and thus lick the excreted blood, they may be extremely dangerous especially to young birds, even if they only feed by nibbling along the feather surface and/or eat epidermal debris. The present paper reports on the successful treatment of different races of fowls being severely infested with both above cited species. This in vivo treatment was done either by a short dipping of the whole fowl into the 1:33 dilution (with tap water) of a neem seed extract (MiteStop®) or by spraying them with the freshly diluted product. It was seen that the dead mallophages dropped down from the feathers as soon as they were dry again. As a precaution, a second treatment was done by some owners 1 week after the first one in order to eliminate all stages, which eventually might have hatched from untouched nits during the time interval between the two treatments. When controlling the treated fowls 4 weeks after the treatment, in no case (treated once or twice), living motile stages were diagnosed indicating the high efficacy of this nontoxic neem seed extract. When treating in vitro cutoff feathers contaminated with L. caponis, it was seen under the stereomicroscope, that the mallophages tried to run away from the 1:33 water-diluted active compound indicating that there is also a repellent effect. Treated L. caponis stopped leg movements within 3 min and died on their feathers within 1–20 min. Then, the last slight trembling movements of their legs and convulsions of their intestine stopped finally.     

A case report of the first application of culture epithelial autograft (JACE®) for giant congenital melanocytic nevus after its approval in Japan

Journal of Artificial Organs - In Japan, the JACE® cultured epidermal autograft (CEA) was approved and covered by public healthcare insurance for use in the treatment of giant congenital...     

How will Internet Use Affect the Patient? A Review of Computer Network and Closed Internet-based System Studies and the Implications in Understanding How the Use of the Internet Affects Patient Populations

The widespread use of the Internet by patients is transforming the delivery of health information. Little research has been done, however, to assess the relationship between patients' use of online health resources and self efficacy, behavior or health status. To understand these effects and create a national research agenda, professionals should establish theoretically based studies. This article provides an overview of studies using computer networks and Internet-based closed systems in which a specific population has access to online health tools similar to those available on the Internet. These studies provide a microcosm of the effects Internet use may have on a patient's health-related behaviors. Three areas of proposed research will be explored: content research; process research; and outcomes research.     

Overcoming a “Probable” Diagnosis in Antimitochondrial Antibody Negative Primary Biliary Cirrhosis: Study of 100 Sera and Review of the Literature

Serum anti-mitochondrial antibodies (AMA) are the serological hallmark of primary biliary cirrhosis (PBC), yet up to 15% of PBC sera are AMA negative at routine indirect immunofluorescence (IIF) while being referred to as ??probable?? cases. The diagnostic role of PBC-specific antinuclear antibodies (ANA) remains to be determined. We will report herein data on the accuracy of new laboratory tools for AMA and PBC-specific ANA in a large series of PBC sera that were AMA-negative at IIF. We will also provide a discussion of the history and current status of AMA detection methods. We included IIF AMA-negative PBC sera (n?=?100) and sera from patients with other chronic liver diseases (n?=?104) that had been independently tested for IIF AMA and ANA; sera were blindly tested with an ELISA PBC screening test including two ANA (gp210, sp100) and a triple (pMIT3) AMA recombinant antigens. Among IIF AMA-negative sera, 43/100 (43%) manifested reactivity using the PBC screening test. The same test was positive for 6/104 (5.8%) control sera. IIF AMA-negative/PBC screen-positive sera reacted against pMIT3 (11/43), gp210 (8/43), Sp100 (17/43), both pMIT3 and gp210 (1/43), or both pMIT3 and Sp100 (6/43). Concordance rates between the ANA pattern on HEp-2 cells and specific Sp100 and gp210 ELISA results in AMA-negative subjects were 92% for nuclear dots and Sp100 and 99% for nuclear rim and gp210. Our data confirm the hypothesis that a substantial part of IIF AMA-negative (formerly coined ??probable??) PBC cases manifest disease-specific autoantibodies when tested using newly available tools and thus overcome the previously suggested diagnostic classification. As suggested by the recent literature, we are convinced that the proportion of AMA-negative PBC cases will be significantly minimized by the use of new laboratory methods and recombinant antigens.     

Long-Term Efficacy and Safety of Hizentra® in Patients with Primary Immunodeficiency in Japan,Europe, and the United States: a Review of 7 Phase 3 Trials

Many patients with primary immunodeficiency (PID) require immunoglobulin G (IgG) replacement therapy, delivered as intravenous IgG (IVIG) or subcutaneous IgG (SCIG). We aim to identify trends in efficacy and safety that would not be evident in individual studies of small patient numbers. Seven open-label, Phase 3, prospective, multicenter studies of the efficacy and safety of Hizentra® (a SCIG), conducted in Japan, Europe, and the US were summarized. Overall, 125 unique patients received 15,013 weekly infusions during a total observation period of 250.9 patient-years. Mean weekly doses of Hizentra® were 83.22–221.3 mg/kg body weight; infusion rates per patient (total body rate) were 25.2–49.3 mL/h across studies. The rates of infections and serious bacterial infections were 3.10 and 0.03 events per patient/year, respectively. Annualized rates of days hospitalized due to infection, out of work/school, and prophylactic antibiotic use were 0.95, 5.14, and 36.78 per patient, respectively. For the equivalent monthly dose, weekly Hizentra® SCIG administration resulted in expectedly-increased serum IgG trough levels in patients switching from IVIG, and maintained levels in patients switching from previous SCIG. Adverse events (AEs) totaled 5039 (events/infusion 0.094–0.773), almost all of which were mild/moderate. Three thousand one hundred ninety-seven were considered treatment-related, the most common of which were injection site reactions (2919 events; 0.001–0.592 AEs per infusion). Systemic AEs were very uncommon. The results from these seven studies indicate that Hizentra® therapy was both efficacious and well tolerated during long-term treatment. This is particularly important in patients with PID, who may require lifelong IgG replacement therapy.     

In vivo biological performance of a novel highly bioactive glass-ceramic (Biosilicate®): A biomechanical and histomorphometric study in rat tibial defects

This study aimed to investigate bone responses to a novel bioactive fully crystallized glass-ceramic of the quaternary system P(2)O(5)-Na(2)O-CaO-SiO(2) (Biosilicate?). Although a previous study demonstrated positive effects of Biosilicate? on in vitro bone-like matrix formation, its in vivo effect was not studied yet. Male Wistar rats (n = 40) with tibial defects were used. Four experimental groups were designed to compare this novel biomaterial with a gold standard bioactive material (Bioglass? 45S5), unfilled defects and intact controls. A three-point bending test was performed 20 days after the surgical procedure, as well as the histomorphometric analysis in two regions of interest: cortical bone and medullary canal where the particulate biomaterial was implanted. The biomechanical test revealed a significant increase in the maximum load at failure and stiffness in the Biosilicate? group (vs. control defects), whose values were similar to uninjured bones. There were no differences in the cortical bone parameters in groups with bone defects, but a great deal of woven bone was present surrounding Biosilicate? and Bioglass? 45S5 particulate. Although both bioactive materials supported significant higher bone formation; Biosilicate? was superior to Bioglass? 45S5 in some histomorphometric parameters (bone volume and number of osteoblasts). Regarding bone resorption, Biosilicate? group showed significant higher number of osteoclasts per unit of tissue area than defect and intact controls, despite of the non-significant difference in the osteoclastic surface as percentage of bone surface. This study reveals that the fully crystallized Biosilicate? has good bone-forming and bone-bonding properties.     

XM17 Follitropin Alfa (Ovaleap<Superscript>®</Superscript>): A Review in Reproductive Endocrine Disorders

The subcutaneous recombinant human follicle-stimulating hormone XM17 follitropin alfa (Ovaleap^®) is approved in the EU as a biosimilar of follitropin alfa (Gonal-f^®) for use in all indications for which the reference product is approved, including as a multifollicular stimulant in women undergoing superovulation for assisted reproductive technology (ART) treatment. In a nonblind, phase I study in healthy female volunteers, the pharmacokinetic profile of XM17 follitropin alfa was bioequivalent to that of reference follitropin alfa following single dosing. Moreover, in a multinational, phase III study, the efficacy of XM17 follitropin alfa as a multifollicular stimulant was equivalent to that of reference follitropin alfa in terms of the number of retrieved oocytes (primary endpoint) in women undergoing controlled ovarian stimulation for ART treatment. There were no clinically relevant differences in oocyte quality between XM17 follitropin alfa and reference follitropin alfa, with biochemical, clinical and ongoing pregnancy rates and take-home baby rates not significantly differing between the treatment groups. XM17 follitropin alfa was generally well tolerated in this patient population, with its tolerability profile generally similar to that of reference follitropin alfa and with no new unexpected tolerability concerns identified. Thus, XM17 follitropin alfa is an effective treatment option in patients requiring follitropin alfa therapy for various reproductive endocrine disorders, providing a useful alternative to reference follitropin alfa.     

Evaluation of the ESPLINE® Influenza A &; B-N assay for the detection of influenza A and B in nasopharyngeal aspirates

Several direct antigen tests for the detection of influenza often lack sensitivity compared to immunofluorescence (IF) on the specimens and viral culture (VC). We evaluated the performance of a rapid test, the ESPLINE® Influenza A &; B-N assay. A total of 302 respiratory specimens were collected at the University Hospital of Antwerp. A first group of 60 samples taken during the H1N1 outbreak (2009–2010) and a second group of 242 samples stored during the seasonal influenza epidemics (2000–2009) were analyzed with the ESPLINE® test. A subset of samples were also evaluated with the BinaxNOW Influenza and the Clearview Exact Influenza. The results were compared to IF on the specimens, VC with IF, and the combination of both, which was considered as the gold standard. The ESPLINE® test’s overall sensitivity and specificity were 91% and 97%, during the H1N1 season 80% and 93%, and for the detection of seasonal influenza 93% and 97%, respectively. In comparison to the BinaxNOW Influenza and the Clearview Exact Influenza, all tests demonstrated a similar specificity of 92.0–100% but a significantly different sensitivity of 44.4–86.0%, with the ESPLINE® test being significantly more sensitive. Due to its very good performance and simplicity, the ESPLINE® test facilitates urgent testing. The test seems less sensitive to detect H1N1 compared to seasonal influenza, although the difference is borderline not significant (p?=?0.067).     

Corrigendum to: “Oral estradiol and dydrogesterone combination therapy in postmenopausal women: Review of efficacy and safety” [Maturitas 76 (2013) 10–21]

HRT is known to be effective for the relief of menopausal symptoms and prevention of osteoporosis. HRT should be tailored to the woman, enhancing the beneficial effects of the treatment while minimizing the risks. It is difficult to evaluate data on particular preparations of HRT and the different dosages in isolation. The purpose of this review is to highlight the efficacy and safety specific to oral estradiol and dydrogesterone combinations of four different dose strengths. A systematic literature search using Medline was carried out to identify studies containing efficacy or safety data. The findings of the retrieved publications confirm that estradiol and dydrogesterone combinations give very effective menopausal symptom relief and prevention of osteoporosis (second line) whilst maintaining a good safety profile.