Juvenile toxicity: are we asking the right questions?

The recent increase in numbers of juvenile toxicity studies over the past few years has doubtless added to our knowledge of the development of organ systems in the young rodent, but it is perhaps rather more difficult to answer the questions as to whether this body of work has served us well in terms of assessing risk in the pediatric population. If there are shortcomings, are they the result of poor study design or poor sensitivity of the model, or are the wrong questions being posed? This article provides a superficial overview of the progress made thus far and considers which aspects of study design and model choice currently fail to adequately address the major issues surrounding pediatric toxicology.     

Ankle brachial index measurement in primary care: are we doing it right?

Background

The reference standard for diagnosing peripheral arterial disease in primary care is the ankle brachial index (ABI). Various methods to measure ankle and brachial blood pressures and to calculate the index are described.

Aim

To compare the ABI measurements performed in primary care with those performed in the vascular laboratory. Furthermore, an inventory was made of methods used to determine the ABI in primary care.

Design of study

Cross-sectional study.

Setting

Primary care practice and outpatient clinic.

Method

Consecutive patients suspected of peripheral arterial disease based on ABI assessment in primary care practices were included. The ABI measurements were repeated in the vascular laboratory. Referring GPs were interviewed about method of measurement and calculation of the index. From each patient the leg with the lower ABI was used for analysis.

Results

Ninety-nine patients of 45 primary care practices with a mean ABI of 0.80 (standard deviation [SD] = 0.27) were included. The mean ABI as measured in the vascular laboratory was 0.82 (SD = 0.26). A Bland–Altman plot demonstrated great variability between ABI measurements in primary care practice and the vascular laboratory. Both method of blood pressure measurements and method of calculating the ABI differed greatly between primary care practices.

Conclusion

This study demonstrates that the ABI is often not correctly determined in primary care practice. This phenomenon seems to be due to inaccurate methods for both blood pressure measurements and calculation of the index. A guideline for determining the ABI with a hand-held Doppler, and a training programme seem necessary.     

Biomarker-driven care in asthma: are we there?

Clinical asthma management is limited by the lack of straightforward and clinically applicable techniques to assess control and appropriately adjust therapy. The availability of biomarkers associated with airway caliber, responsiveness, or inflammation has prompted interest in the application of these measures as surrogate asthma end points in clinical trials. Use of a biomarker as a surrogate outcome in practice is most appropriate in settings in which the effects of therapy on clinical disease, as experienced by patients, are fully captured by that biomarker. Recent studies suggest that although asthma therapies can alter various biomarkers, the relationship between these biomarker changes and important clinical outcomes is inconsistent. Because symptom-driven titration of therapy is feasible and effective, additional data demonstrating clinically important benefits of biomarker-driven care in asthma are needed to justify the logistic and economic burdens associated with clinical dissemination of these techniques.     

Are we getting enough allergens?

This paper proposes that reduced allergen exposure is one of the factors underlying the higher risk of IgE-mediated allergic disease in populations with an urbanized, westernized, and affluent lifestyle. This lower allergen exposure results in the failure to induce and maintain immune tolerance to common environmental allergens. The paper summarizes different lines of evidence that may support or contradict this hypothesis and points to areas where more knowledge is needed.     

Antisperm contraceptive vaccines: where we are and where we are going?

This is a review of current status and future perspectives on the development of antisperm contraceptive vaccines (CV) and immunocontraceptives. The development of antisperm CV is an exciting proposition. There is a strong rationale and recent data indicating that this proposition can translate into reality. The search for novel sperm-specific antigens/genes, that can be used for CV, continues using various recent developing technologies. Various approaches of proteomics, genomics, reproductive biology, mucosal immunity and vaccinology and several novel technologies such as gene knockout technology, phage display technology, antibody engineering, differential display technique, subtractive hybridization, and hybridoma technology are being used to delineate sperm-specific antigens and construct CV. Various sperm antigens/genes have been delineated, cloned, and sequenced from various laboratories. Vaccination with these sperm antigens (recombinant/synthetic peptide/DNA) causes a reversible contraceptive effect in females and males of various animal species, by inducing a systemic and local antisperm antibody response. The efficacy is enhanced by combination vaccination, including peptides based on various sperm antigens. Several human novel scFv antibodies with unique complementarity-determining regions (CDRs), that react with specific well-defined fertility-related sperm antigens, have been synthesized. These human infertility-related antibodies may find application in the development of novel immunocontraceptives. Besides finding the novel sperm antigens, the present and future focus is on enhancing the immunogenicity, bioefficacy, and on obliterating the inter-individual variability of the immune response, and proceeding for primate and human clinical trials. Multi-epitope vaccines combining sperm proteins involved in various steps of fertilization cascade have been found to enhance the immunogenicity and bioefficacy of the contraceptive effect. The in vitro synthesis of infertility-related human scFv antibodies may provide unique once-a-month immunocontraceptives, the first of its kind, for human use. The multi-epitope CV and preformed engineered human antibodies of defined specificity may obliterate the concern related to inter-individual variability of the immune response.     

A closer look revisited: are we subjects or are we donors?

The author offers personal reflections on the implications of the article “Managing Incidental Findings & Research Results in Genomic Research Involving Biobanks & Archived Datasets” in terms of how the article addresses serious knowledge disparities and differing expectations between participants and researchers.Genet Med 2012:14(4):458–460     

Critical care: Are we customer friendly?

Objective:Assessing and enhancing family satisfaction are imperative for the provision of comprehensive intensive care. There is a paucity of Indian data exploring family''s perception of Intensive Care Unit (ICU) patients. We wanted to explore family satisfaction and whether it differed in families of patients admitted under intensivists and nonintensivists in our semi-open ICU.Methodology:We surveyed family members of 200 consecutive patients, between March and September 2009 who were in ICU for >3 days. An internationally validated family satisfaction survey was adapted and was administered to a family member, on day 4 of the patient''s stay. The survey consisted of 15 questions in five categories - patient care, medical counseling, staff interaction, visiting hours, and facilities and was set to a Likert scale of 1–4. Mean, median, and proportions were computed to describe answers for each question and category.Results:A total of 515 patients were admitted during the study period, of which 200 patients stayed in the ICU >3 days. One family member each of the 200 patients completed the survey with 100% response rate. Families reported the greatest satisfaction with patient care (94.5%) and least satisfaction with visiting hours (60.5%). Chi-square tests performed for each of the five categories revealed no significant difference between satisfaction scores of intensivists and nonintensivists'' patients.Conclusion:Family members of ICU patients were satisfied with current care and communication, irrespective of whether they were admitted under intensivists or nonintensivists. Family members preferred open visiting hours policy than a time limited one.     

Technology and managed care: is telemedicine the right tool for rural communities?

Telemedicine offers a unique opportunity for the delivery of healthcare to rural communities. For this opportunity to be realized, telemedicine services need to be planned carefully with attention to acceptance by clients and providers, economic viability and effective administration. To be sustainable, services for rural populations must be supported by a well-defined and resourced infrastructure. Managed care, considered as an approach to the effective delivery of appropriate services, is indeed the right tool for rural communities. Cost savings will be an important issue for health care managers, but rural telemedicine services should be considered in a broader economic perspective, taking account of both costs and benefits from various perspectives, and considering long term outcomes.