Fluzone(®) Intradermal vaccine: a promising new chance to increase the acceptability of influenza vaccination in adults

On May 9 2011, the US FDA approved Sanofi Pasteur's Fluzone(?) Intradermal influenza vaccine, the first influenza vaccine licensed in the USA that uses a new microinjection system for intradermal delivery of vaccines (Soluvia?, Becton Dickinson). Its antigen content is lower (9 μg hemagglutinin per strain) than the conventional intramuscular vaccine (15 μg) and it is indicated for active immunization of adults aged between 18 and 64 years. Data from the clinical trial assessing immunogenicity and safety of Fluzone Intradermal in adults were consistent with substantial experience accumulated with Intanza(?) 9 μg, the intradermal vaccine licensed on February 26 2009 and launched during the 2010/2011 season in Europe. Fluzone Intradermal is safe and its immunogenicity comparable with that of conventional intramuscular vaccines. Obtaining optimal acceptability of intradermal vaccines may represent an additional asset to help increase the coverage of influenza vaccination in young adults.     

Can influenza H1N1 vaccination lead to the membranous glomerulonephritis?

In 2009 winter, Influenza A (H1N1) monovalent split virus vaccine was used prevalently in the whole world as a result of the pandemic caused by Influenza (H1N1) virus. The vaccine's adverse effects were observed closely and vaccination has been found as safe in most studies. But some reports about immune response related diseases after influenza vaccinations are remarkable. The close relationship between membranous glomerulonephritis and antigens is known, particularly in seconder forms which occur after viral infections and vaccinations. So this case report is about a 56-year-old man, who developed membranous glomerulonephritis 23 days after the vaccination against Influenza A (H1N1) virus.     

DNA vaccination: the answer to stable,protective T-cell memory?

Distinct populations of both CD4(+) and CD8(+) memory T cells have been identified on the basis of their location (lymphoid versus non-lymphoid tissues) and function. There have been several recent advances in our understanding of the factors that govern the generation and maintenance of T-cell memory in vivo. Utilising this knowledge could contribute to the refinement of DNA vaccine technology to induce more robust and longer-lasting protective T-cell based immunity.     

Are age-based strategies effective in increasing influenza vaccination coverage?: the Spanish experience

We investigated the effectiveness of applying age-based strategies to improve influenza vaccination coverage in Spain. We described and compared influenza vaccination coverage from 2003 to 2010 between those Spanish autonomous regions (AR) that lowered the age limit to 60 y and those regions that maintained the limit at 65 y. We used data collected from two surveys covering a representative sample of the Spanish population aged ≥ 16 y [Spanish National Health Survey (SNHS) 2003/2004 and the European Health Survey for Spain (EHSS) 2009/2010]. The study population (persons aged ≥ 60 y) comprised 7,496 persons in the SNHS and 7,686 in the EHSS. In 2010, those AR which had reduced the age limit had higher coverage for all age groups analyzed-regardless of the presence of associated chronic conditions-than AR which continued vaccination for those ≥ 65 y. The greatest differences appeared in individuals aged 60 to 64 y (36.9% vs. 24.4% for individuals without chronic conditions, 59.1% vs. 52.9% for those with chronic conditions, and 43.3% vs. 32.3% for the entire age group). Multivariate analysis showed that those AR which lowered the age limit increased total coverage for all age groups, specifically among individuals with chronic conditions aged 60 to 64 y (IRR 1.18; 95% CI, 1.01-1.54) and ≥ 65 y (IRR 1.07; 95% CI, 1.00-1.14). No significant changes were observed over time for the AR that continued vaccinating people aged ≥ 65 y. Our results suggest that age-based strategies are effective for improving influenza vaccination coverage in Spain.     

A quantitative model of autoimmune disease and T-cell vaccination: does more mean less?

According to a simple mathematical model, the activated effector T cells that cause an autoimmune disorder can also cure the disease if administered in large doses. This prediction has been tested in the nonobese diabetic (NOD) mouse model and demonstrates that administration of intermediate doses of a diabetogenic T-cell clone caused early hyperglycemia, whereas a higher dose cured the disease. As discussed here by Lee Segel and colleagues, the proposed application of T-cell vaccination to treat clinical disease obliges immunologists to consider the quantitative complexities of regulation.     

Schistocytes: which definition should be taken and which method should be used to identify and count them?

Schistocytes result from red cell fragmentation. The identification of the schistocytes is critical for appropriate management of the patients. We report the results of a survey about the determination of schistocytes. The analysis of the answers of 24 well-trained biologists points out the different approaches used to count these cells, and the urgent need for guidelines to identify and enumerate them.     

Rise time or rise rate: which should be a criterion for analysing motor unit action potentials?

We measured the rise time (RT) and rise rate (RR) of motor unit action potentials (MUAPs) when sharp sounds are heard in concentric EMG in the first dorsal interosseus muscle (FDI) and biceps brachii muscle (BIC) of normal subjects. MUAPs from FDI muscle with an RT of less than 500 microseconds were 85%, and those of more than 500 microseconds were 15%. In contrast, MUAPs from BIC muscle with an RT of less than 500 microseconds were 65%, and those of more than 500 microseconds were 35%. Distributions of the RR for FDI and BIC were also determined. MUAPs from FDI muscle with an RR more than 0.3 mV/ms were 98.3%, and those of less than 0.3 mV/ms were 1.7%. In contrast, MUAPs from BIC muscle with an RR of more than 0.3 mV/ms were 93%, and those of less than 0.3 mV/ms were 7%. We conclude it is better to use RR than RT when accepting MUAPs in clinical EMG, because even when sharp sounds are heard, MUAPs do not always have an RT of less than 500 microseconds. The use of RT and the sharpness of MUAPS therefore need to be reconsidered, or RR should be used in clinical EMG by automatic program.     

Lupus nephritis: When and how often to biopsy and what does it mean?

Renal disease is a frequent complication of SLE which can lead to significant illness and even death. Today, a baseline renal biopsy is highly recommended for all subjects with evidence of lupus nephritis. Biopsy allows the clinician to recognize and classify different forms of autoimmune lupus glomerulonephritis, and to detect other glomerular diseases with variable pathogenesis which are not directly related to autoimmune reactivity, such as lupus podocytopathy. Moreover, not only glomerular diseases, but other severe forms of renal involvement, such as tubulo-interstitial nephritis or thrombotic microangiopathy may be detected by biopsy in lupus patients. Thus, an accurate definition of the nature and severity of renal involvement is mandatory to assess the possible risk of progression and to establish an appropriate treatment.The indications to repeat biopsy are more controversial. Some physicians recommend protocol biopsies to recognize the possible transformation from one class to another one, or to identify silent progression of renal disease, others feel that good clinical monitoring is sufficient to assess prognosis and to make therapeutic decisions. At any rate, although any decision should always be taken by considering the clinical conditions of the patient, there are no doubts that repeat renal biopsy may represent a useful tool in difficult cases to evaluate the response to therapy, to modulate the intensity of treatment, and to predict the long-term renal outcome both in quiescent lupus and in flares of activity.     

Identification and management of familial hypercholesterolaemia: what does it mean to primary care?

Familial hypercholesterolaemia is one of the most common dominantly inherited disorders to be identified in primary care, leading to raised serum cholesterol evident from the first year of life. Around 1 in 500 people are affected by this condition, but less than 15% of these are currently attending lipid clinics, suggesting that the vast majority are unrecognised in general practice. The recently released National Institute for Health and Clinical Excellence evidence-based guideline on the identification and management of familial hypercholesterolaemia provides an opportunity to bridge this gap. Primary care has a role in systematic and opportunistic case finding, such as recognising the relevance of a family history of premature coronary heart disease and/or grossly elevated cholesterol. Although affected individuals need specialist care, GPs can reinforce the information provided by specialists and support cascade screening to other affected members of the extended family.     

Surgical sperm recovery for intracytoplasmic sperm injection: which method is to be preferred?

Different methods for recovering epididymal or testicular spermatozoa have been described and each has its drawbacks and advantages. Percutaneous aspiration of the testis may be the method of choice in cases of irreparable obstructive azoospermia. Using a 21-gauge needle, spermatozoa may be recovered in 96 % of patients. More patients undergoing fine-needle aspiration experienced less pain than expected as compared with those undergoing open biopsy. Microsurgical epididymal sperm aspiration (MESA) is the preferred method in patients with an incomplete work-up because, if indicated, a vasoepididymostomy can be performed concomitantly with a full scrotal exploration. In azoospermic patients with testicular failure, the sperm recovery rate, i.e. the chance of finding at least one spermatozoon, is around 50% after multiple open biopsies. However, the fertilization rates after intracytoplasmic sperm injection (ICSI) are significantly lower than in men with normal spermatogenesis, and complete fertilization failure may occur more frequently. Although the combination of testicular sperm extraction (TESE) and ICSI may be the sole treatment available for infertility because of non-obstructive azoospermia, the overall success rate is limited and ongoing pregnancies are obtained in < or =20% of ICSI cycles. In patients with incomplete Sertoli cell-only syndrome, testicular damage may be limited by use of a selective microsurgical approach; less invasive methods such as fine-needle aspiration are not useful in these patients. Of 14 patients with primary testicular failure as proven by histopathology, only in one case (7.1%) were spermatozoa recovered by multiple aspirations, while in nine cases (64.3%) spermatozoa were recovered by open biopsy. Although the pregnancy rates reported after ICSI with frozen-thawed testicular spermatozoa from patients with primary testicular failure are relatively low, the recovery of testicular spermatozoa by open biopsy followed by cryopreservation may be the method of choice by which to prevent repeat surgery and pointless ovarian stimulation in the female partner.     

The clinical evaluation of HER‐2 status: which test to use?

Accurate determination of the status of the type I receptor tyrosine kinase HER-2 in breast carcinomas provides significant insight into patient prognosis and may also inform selection of chemotherapeutic and hormonal treatments. At present, however, the single most important application of HER-2 testing is in the selection of patients for treatment with targeted therapies such as Herceptin. Although, based on current literature, fluorescence in situ hybridization (FISH) detection of HER-2 gene amplification may provide more accurate information in this context, this method is not yet widely available. Therefore, screening by immunohistochemistry (IHC) for HER-2 protein, backed by rigorous quality controls and FISH testing of equivocal cases with intermediate staining intensity, remains the current practice. In laboratories with highly standardized testing and quality assurance procedures, this protocol appears highly effective. Improvements in fixation procedures, standardization of antibodies, and use of automated image analysis may all increase the precision of IHC testing. However, on the basis of current data, there is a case to be made for the wider implementation of FISH testing to determine HER-2 status in breast cancer.     

Criteria for fairly allocating scarce health-care resources to genetic tests: which matter most?

The use of genetic tests is expanding rapidly. Given limited health-care budgets throughout Europe and few national coverage decisions specifically for genetic tests, decisions about allocating scarce resources to genetic tests are frequently ad hoc and left to lower-level decision makers. This study assesses substantive ethical and economic criteria to prioritize genetic services in a reasonable and fair manner. Principles for allocating health-care resources can be classified into four categories: need-based allocation; maximizing total benefits; treating people equally; and promoting and rewarding social usefulness. In the face of scarcity, the degree of an individual''s need for medical intervention is an important criterion. Also, different economic concepts of efficiency are of relevance in the theory and practice of prioritizing genetic tests. Equity concerns are most likely to be relevant in terms of avoiding undesirable inequities, which may also set boundaries to the use of efficiency as a prioritization criterion. The aim of promoting and rewarding social usefulness is unlikely to be relevant to the question of what priority a genetic test should have in clinical practice. Further work is needed to select an appropriate set of criteria; operationalize them; and assign weights before some kind of standardized priority information can be added to information sources for genetic services. Besides the substantive criteria, formal considerations like those pointed out in the framework of accountability for reasonableness need to be considered in decision making.