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Objectives: To identify and summarize published systematic reviews that report results of meta-analyses that combined direct and indirect comparisons. Study Design and Setting: Narrative review of mixed treatment comparisons (MTCs) reported in systematic reviews of health interventions. MEDLINE, MEDLINE In-Process, Embase, CINAHL, DARE, the Cochrane Database of Systematic Reviews, and SIGLE were searched for reviews published up to June 2012 in which a meta-analysis had been conducted that combined direct and indirect comparisons among more than two interventions. Results: Reviews reporting MTCs are difficult to identify when searching major databases. These databases offer no way to identify MTCs, and authors use various names when reporting them. Of the 201 eligible reviews identified, more than three-quarters had been published in full. MTC methods have been used to study a wide range of clinical topics. The reported use of these methods has increased rapidly since 2009, and results from MTCs are commonly used in health policy decisions, through the evidence considered in health technology assessments. Conclusion: In view of the increasing use of MTCs, indexing of this study type in databases and a consensus on terminology and standards for conduct and reporting would be timely. [ABSTRACT FROM AUTHOR]

Abstract: Background: A hepatitis B vaccine was manufactured with a modified process (mpHBV) that incorporated double the usual amount of phosphate. Following a study in young adults, the mpHBV was evaluated in infants in a combination hepatitis B and Haemophilus influenzae B vaccine (mpHBV–Hib). Methods: The mpHBV–Hib was compared with the licensed bivalent HBV–Hib vaccine Comvax™ for immunogenicity and safety. Both vaccines contained 5μg/0.5mL of hepatitis B surface antigen (HBsAg) and 7.5μg/0.5mL of PRP-OMPC (polyribosylribitol phosphate outer membrane protein complex). A total of 543 infants were randomized 1:1 to receive either vaccine at 2, 4 and 12 months of age. A pneumococcal conjugate vaccine (PCV) was given concomitantly. Immunogenicity was assessed at 1-month post-dose 3. Results: Seroprotection rates [% subjects with anti-hepatitis B surface antigen antibody titers (anti-HBs) ≥10mIU/mL)] were 100% and 99% for mpHBV–Hib and the licensed control (Comvax™), respectively. Anti-HBs geometric mean titers (GMTs) were 4204 (95% CI, 3411–5182) and 1683 (95% CI, 1350–2099)mIU/mL, respectively. Anti-PRP seroprotection rates (SPR) at ≥0.15μg/mL and at ≥1.0μg/mL were 97% and 94%, respectively, for mpHBV–Hib and 96% and 92%, respectively, for the control. Anti-PRP GMTs were 7.1μg/mL for mpHBV–Hib and 8.0μg/mL for the control. Reactogenicity of the two vaccines was similar. Conclusions: The mpHBV in combination with Hib and with co-administered PCV was highly immunogenic. The safety profile of mpHBV–Hib was comparable to the licensed control. Both the control and mpHBV–Hib met acceptability criteria for seroprotection rates to hepatitis B, with higher anti-HBs GMTs noted for mpHBV–Hib. [Copyright &y& Elsevier]

Abstract: Human cytomegalovirus (HCMV) productively infects CD34+ progenitor-derived, mature Langerhans-type dendritic cells (matLC) and reduces surface expression of MHC class II complexes (MHC II) by increasing intracellular retention of these molecules. To determine whether HCMV also inhibits MHC II expression by other mechanisms, we assessed mRNA levels of the class II transcriptional regulator, CIITA, and several of its target genes in infected matLC. Levels of CIITA, HLA-DRA (DRA) and DRB transcripts, and new DR protein synthesis were compared in mock-infected and HCMV-infected cells by quantitative PCR and pulse-chase immunoprecipitation analyses, respectively. CIITA mRNA levels were significantly lower in HCMV-infected matLC as compared to mock-infected cells. When assessed in the presence of Actinomycin D, the stability of CIITA transcripts was not diminished by HCMV. Analysis of promoter-specific CIITA isoforms revealed that types I, III and IV all were decreased by HCMV, a result that differs from changes after incubation of these cells with lipopolysaccharide (LPS). Exposure to UV-inactivated virus failed to reduce CIITA mRNA levels, implicating de novo viral gene expression in this effect. HCMV-infected matLC also expressed lower levels of DR transcripts and reduced DR protein synthesis rates compared to mock-infected matLC. In summary, we demonstrate that HCMV infection of a human dendritic cell subset inhibits constitutive CIITA expression, most likely at the transcriptional level, resulting in reduced MHC II biosynthesis. We suggest this represents a new mechanism of modulation of mature LC by HCMV. [Copyright &y& Elsevier]

Abstract: Pituitary gland metastases, albeit rare, remain an important differential in sellar and suprasellar tumours. Clinical and radiological features of pituitary metastases may be indistinguishable from benign suprasellar lesions such as a pituitary adenoma. Histopathology with immunohistochemical assay remains the key to the diagnosis of pituitary metastasis. We describe four patients with sellar lesions presenting with anterior visual pathway compression initially diagnosed as pituitary adenomas who on immunohistochemistry were found to have metastases to the pituitary. Classification of the cell histology determined the primary site of origin in some patients. This series demonstrates the importance of combining histopathology and immunohistochemistry in the diagnosis of suprasellar lesions. [Copyright &y& Elsevier]

Abstract: A 70-year-old woman with a 46-year history of Graves disease had significant thyroid related orbitopathy (TRO) requiring previous bilateral orbital decompressions and one previous strabismus procedure for an exotropia of 60 PD. At the initial neuro-ophthalmology assessment, she had an exotropia of 20 PD and was scheduled for further surgery, but at the time of a second assessment a few weeks later, her strabismus had markedly changed. Accordingly, the patient underwent a neostigmine bromide test that demonstrated evidence of co-existing myasthenia gravis. [Copyright &y& Elsevier]

Abstract: Functional visual loss (FVL) refers to subnormal vision or altered visual fields where no underlying pathology of the visual system can be found. It may be seen in a continuum from frank malingering to hysteria. FVL may first present to the general practitioner or physician and the financial burden of evaluation and potential disability-related claims may be substantial. Diagnosis relies on a high index of suspicion and demonstration with a few simple tests that the patient has better vision than alleged. The aim of this review is to provide a practical approach to examination of patients with suspected functional visual loss. An accurate and early diagnosis of FVL starts with a high index of suspicion. Only a few of the tests need to be learned well, performed smoothly and confidently. These clinical tests obviate the need to perform expensive imaging such as magnetic resonance imaging and if used in the correct setting have the potential to reduce further the cost of diagnosis. Management requires an understanding approach and confrontation is seldom helpful. It is important to stress to the patient that FVL has a good prognosis, thereby providing “a way out” and giving the patient the opportunity to recover. [Copyright &y& Elsevier]

Dendritic cells (DCs) can induce tumor- or pathogen-specific T cell responses in humans. We comprehensively compared the clinically available DC maturation stimuli for their ability to promote uniformly mature DCs that elicit higher levels of T cell responses. We compared the standard maturation stimulus, autologous monocyte-conditioned medium (MCM), with a synthetic double stranded RNA (poly I:C), soluble CD40 ligand trimer, and a defined cocktail of cytokines (TNF-α, IL-1β, IL-6) and PGE2 to promote mature phenotype and function in human monocyte-derived DCs. The cocktail was the most efficient despite the lack of induction of IL-12p70. While these results support the use of the MCM-mimic cocktail in clinical DC immunotherapy trials, the roles of it’s individual constituents remain to be completely defined. [Copyright &y& Elsevier]

DTaP-IPV-Hib-HepB is a fully-liquid, hexavalent combination vaccine (Vaxelis™) approved for vaccination against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, and invasive disease due to Haemophilus influenzae type b (Hib). Hib capsular polysaccharide, polyribosylribitol phosphate (PRP), is conjugated to Neisseria meningitidis outer membrane protein complex (OMPC). Safety and immunogenicity of DTaP-IPV-Hib-HepB were evaluated in 6 Phase III clinical studies including > 5,200 children. Studies included vaccination schedules in the United States (2, 4, 6 months of age) and Europe (2, 3, 4, 12 months of age and 2,4,11–12 months of age). Data pertaining to anti-PRP responses of DTaP-IPV-Hib-Hep B compared to control vaccines from 5 Phase III studies are summarized. Post-infant series, the percentage of participants that achieved protective antibody thresholds for PRP (anti-PRP titer ≥ 0.15 μg/mL and ≥ 1.0 μg/mL, respectively) were higher in DTaP-IPV-Hib-HepB recipients compared to recipients who received control vaccines. A high level of protective responses (96.6% at ≥ 0.15 μg/mL [95% CI:94.8, 97.9%]; 72.9% at ≥ 1.0 μg/mL [95% CI:69.2,76.4%]) were seen post-dose 2 of the 2 + 1 vaccination schedule and met superiority criteria over comparator, p-value < 0.001. In the same schedule, prior to administration of the toddler dose (in the second year of life), anti-PRP titers were higher in DTaP-IPV-Hib-HepB recipients (91.4% at ≥ 0.15 μg/mL; 46.8% at ≥ 1.0 μg/mL) as compared to recipients who received control vaccines (63.4% at ≥ 0.15 μg/mL; 17.1% at ≥ 1.0 μg/mL). One-month post-toddler dose, high levels of anti-PRP titers were achieved in both DTaP-IPV-Hib-HepB recipients (99.8% at ≥ 0.15 μg/mL; 96.6% at ≥ 1.0 μg/mL) and recipients who received control vaccines (99.5% at ≥ 0.15 μg/mL; 94.9% at ≥ 1.0 μg/mL). These results support that DTaP-IPV-Hib-HepB induces a robust and sustained early Hib response. During the high-risk period for Hib disease after the infant vaccine and prior to the toddler dose; >90% of recipients maintained superior protective anti-PRP levels compared to control. [ABSTRACT FROM AUTHOR]

Background Combination vaccines simplify vaccination visits and improve coverage and timeliness. DTaP5-HB-IPV-Hib is a new investigational, fully-liquid, combination vaccine designed to protect against 6 infectious diseases, including 5 pertussis antigens and OMPC instead of PT as conjugated protein for Hib component. Methods In this multicenter, double-blind, comparator-controlled, Phase III study (NCT01480258) conducted in Sweden, Italy, and Finland, healthy infants were randomized 1:1 to receive one two immunization regimens. The DTaP5-HB-IPV-Hib Group received the investigational hexavalent vaccine (DTaP5-HB-IPV-Hib) and the Control Group received Infanrix-hexa (DTPa3-HBV-IPV/Hib) at 2, 4 and 11–12 months of age. Both groups received concomitantly Prevnar 13 (PCV13) and Rotateq (RV5) or Rotarix (RV1) at 2, 4 months of age and PCV13 at 11–12 months. Subjects administered RV5 received a 3rd dose at 5 months of age. Results A total of 656 subjects were randomized to the DTaP5-HB-IPV-Hib Group and 659 subjects to Control Group. Immune responses to all vaccine antigens post-toddler dose were non-inferior in the DTaP5-HB-IPV-Hib Group as compared to the Control Group. Additionally, the post-dose 2 and pre-toddler DTaP5-HB-IPV-Hib anti-PRP responses were superior. The DTaP5-HB-IPV-Hib Group responses to concomitant RV1 were non-inferior compared to the Control Group. Solicited adverse event rates after any dose were similar in both groups, except for higher rates of pyrexia (6.4% difference; 95% CI: 1.5, 11.3) and somnolence (5.8% difference; 95% CI: 1.7, 9.8) in the DTaP5-HB-IPV-Hib Group. Vaccine-related serious adverse events occurred infrequently in the DTaP5-HB-IPV-Hib Group (0.3%) and the Control Group (0.5%). Conclusions The safety and immunogenicity of DTaP5-HB-IPV-Hib is generally comparable to Control when administered in the 2, 4, 11–12 month schedule. Early Hib responses were superior versus Control. DTaP5-HB-IPV-Hib could provide a new hexavalent option for pediatric combination vaccines, aligned with recommended immunizations in Europe. Study identification: V419-008 CLINICALTRIALS.GOV identifier: NCT01480258 [ABSTRACT FROM AUTHOR]