Preventing transmission: plant-derived microbicides and mucosal vaccines for reproductive health

Exclusion of infectious agents from mucosal surfaces of the reproductive tract is a key objective of microbicides and mucosal vaccines. With mucosal antibodies as a common mechanism of exclusion, parallel development of passive and active immunization strategies is an opportunity to determine and achieve protective antibody concentrations in the female reproductive tract. Recognizing that access to sexual and reproductive health products will require low-cost and high-capacity production technologies, the emerging tools of plant biotechnology for complex biopharmaceutical production are crucial. Unfortunately, few preclinical or clinical studies have been completed to date with plant-derived agents intended for reproductive health.     

Researching illness and injury: methodological considerations

Circumstances surrounding the physical condition of the critically ill, the injured, and the dying make the conduct of qualitative research particularly difficult. Assumptions embedded in qualitative research are challenged or no longer apply: As sick people, participants are unfamiliar with their everyday worlds, and they are often incapable of describing their conditions and perceptions, so that researchers have difficulty obtaining data to comprehend, interpret, and generally conduct their research. Methodological problems extending from the participants' condition include the lack of everyday language to describe their experiences, the instability of the participants' reality, and the instability of the self. When researching participants who are sick, these methodological problems result in decisions about the timing of data collection, challenges to validity and reliability, and debates about who should be conducting this research.     

New biomedical approaches for sexually transmitted infection prevention: vaccines and microbicides

STIs are a major global health problem. Biomedical strategies are under development that will help prevent these infections. Vaccines against C. trachomatis and N. gonorrhoeae are in early stages of development. Stage-III trials are underway on prophylactic vaccines for HPV and HSV-2. Strategies focused on immunizing only high-risk individuals are unlikely to stem the tide of STIs. Approaches to widespread immunization require acceptance of such vaccines by health care providers, institutions providing funding, parents, and adolescents. Microbicides offer a female-controlled method for protection from STIs. They use many strategies to prevent infection. These products are at various stages of development. It seems that young women and teenagers would be interested in using microbicides. Correct and consistent use of microbicides will require taking women's preferences into account during product development and marketing.     

Condom avoidance and determinants of demand for male circumcision in Johannesburg, South Africa

BACKGROUND Circumcision is efficacious in reducing HIV acquisition in heterosexual males. The South Africa government has been reluctant to adopt a national circumcision programme, possibly due to concerns that circumcision may result in decreased condom use. OBJECTIVE To identify the determinants of demand for male circumcision, to examine variations by ethnicity, and to determine whether it is demanded to avoid condom use. METHODS 403 parents and 237 sons in Johannesburg, South Africa, were recruited through a randomized household survey, with oversampling to balance between blacks (n = 220), 'coloured' (mixed ethnicity) (n = 202) and whites (n = 218). The demand for male circumcision was estimated using a conjoint analysis, with each respondent randomly receiving four tasks comparing seven possible benefits-six identified through key informant interviews and one for condom avoidance. Respondents' choices were analysed using logistic regression, including stratified analyses to test for homogeneity. RESULTS Overall, circumcision's beneficial effects on HIV transmission (P < 0.001), sexually transmitted infection (STI) transmission (P?< 0.001), hygiene (P < 0.05) and sex (P < 0.05) were identified as determinants of demand, but the condom avoidance hypothesis was rejected as it was 'repulsive' to respondents (P < 0.001). Consistent results were found for blacks (P < 0.001) and coloured (P < 0.001), but not for whites who found condom avoidance attractive (P < 0.04), a result not explained by variations in wealth, age or paternal circumcision status. CONCLUSIONS Male circumcision programmes should be tailored to accommodate variations in the determinants of demand across the target population. We find that circumcision's protective effect against HIV acquisition in men is the only determinant to be found consistently across all ethnic groups in Johannesburg. We also find that concerns over condom avoidance may have been overstated. This said, male circumcision strategies should reinforce a range of HIV prevention strategies, including condom use, as we find evidence that whites may view circumcision as a means to avoid condom use.     

Estimates of HIV-1 incidence based on serological methods: a brief methodological review

The paper reviews the serological methods employed in the estimation of HIV incidence based on cross-sectional studies, as well as the main findings from studies carried out in Brazil that have used such methods. Each method is briefly described, as well as their advantages and limitations. The different methods are also analyzed as a set of complementary but sometimes contradictory strategies under permanent criticism and review, still far from a gold standard. Finally, an additional question--central to the accurate monitoring of the AIDS epidemic using such methods--is discussed: whether the different methods should or should not be adjusted. The debate is open and controversy should be viewed as an unavoidable consequence of a very dynamic research field, informed by the progress in sciences as diverse as epidemiology, biostatistics, mathematical modeling and different branches of basic science, such as immunology, virology, and molecular biology.     

Geographically linking population and facility surveys: methodological considerations

Background

The relationship between health services and population outcomes is an important area of public health research that requires bringing together data on outcomes and the relevant service environment. Linking independent, existing datasets geographically is potentially an efficient approach; however, it raises a number of methodological issues which have not been extensively explored. This sensitivity analysis explores the potential misclassification error introduced when a sample rather than a census of health facilities is used and when household survey clusters are geographically displaced for confidentiality.

Methods

Using the 2007 Rwanda Service Provision Assessment (RSPA) of all public health facilities and the 2007–2008 Rwanda Interim Demographic and Health Survey (RIDHS), five health facility samples and five household cluster displacements were created to simulate typical SPA samples and household cluster datasets. Facility datasets were matched with cluster datasets to create 36 paired datasets. Four geographic techniques were employed to link clusters with facilities in each paired dataset. The links between clusters and facilities were operationalized by creating health service variables from the RSPA and attaching them to linked RIDHS clusters. Comparisons between the original facility census and undisplaced clusters dataset with the multiple samples and displaced clusters datasets enabled measurement of error due to sampling and displacement.

Results

Facility sampling produced larger misclassification errors than cluster displacement, underestimating access to services. Distance to the nearest facility was misclassified for over 50% of the clusters when directly linked, while linking to all facilities within an administrative boundary produced the lowest misclassification error. Measuring relative service environment produced equally poor results with over half of the clusters assigned to the incorrect quintile when linked with a sample of facilities and more than one-third misclassified due to displacement.

Conclusions

At low levels of geographic disaggregation, linking independent facility samples and household clusters is not recommended. Linking facility census data with population data at the cluster level is possible, but misclassification errors associated with geographic displacement of clusters will bias estimates of relationships between service environment and health outcomes. The potential need to link facility and population-based data requires consideration when designing a facility survey.

     

A review of injury epidemiology in the UK and Europe: some methodological considerations in constructing rates

Background  

Serious injuries have been stated as a public health priority in the UK. However, there appears to be a lack of information on population-based rates of serious injury (as defined by a recognised taxonomy of injury severity) at national level from either official statistics or research papers. We aim to address this through a search and review of literature primarily focused within the UK and Europe.     

Gas inertia and ventilatory measurements under pressure: methodological considerations

A bag-in-box apparatus with a spirometer was used to measure the ventilatory minute volume in subjects exercising at air pressures up to 6.8 atm. During rest there was good agreement between minute volumes derived from the expired gas in the bag and the sum of tidal volumes from the spirometer, whereas during exercise the bag volume exceeded the spirometer volume by up to 20%. This was found to be due to the inertia of high density gas in the breathing hoses. Given sufficient flow rate the gas would continue to flow from the box to the bag following end expiration and end inspiration. The spirometer would not record this because it only responds to changes in the sum of box and bag volumes, whereas emptying the bag through a gas meter records the volume of gas actually moved. A model was constructed to investigate the phenomenon. It was concluded that many different conventional setups for respiratory measurements may be subject to this type of error. Solutions to the problem include a collapsible tube section downstream from the subject, pneumotachometers, chest-mounted magnetometers, or inductive plethysmographs.     

Researching domestic violence against women: methodological and ethical considerations

The results of three population-based studies on violence against women in Nicaragua are compared in this article. Two of the studies were regional in scope (León and Managua) and focused specifically on women's experiences of violence, whereas the third study was a Demographic and Health Survey (DHS) conducted with a nationally representative sample of women. The lifetime prevalence estimates for women's undergoing physical violence from a partner were significantly higher in the León study (52 percent) and Managua study (69 percent), compared with that given in the DHS (28 percent). Possible explanations for the differences are examined through pooled multivariate logistic regression analysis, as well as analysis of six focus-group discussions carried out with field-workers and staff from the three studies. The most important differences that were found concerned ethical and safety procedures and the interview setting. The results indicate that prevalence estimates for violence are highly sensitive to methodological factors, and that underreporting is a significant threat to validity.     

Frequent attenders in general practice care: a literature review with special reference to methodological considerations

OBJECTIVE: To describe the basis on which our knowledge of frequent attendance in general practice rests and to propose recommendations for further research on frequent attenders (FAs). DESIGN: The literature review (finished February 2004) encompassed peer-reviewed articles in English describing contacts with general practice in terms of frequency. Searches were performed in the Medline, CINAHL, EMBASE, PsycINFO, Social Sciences Expanded Index and ISI Citation databases with additional searches in reference lists and the 'related articles' function in the ISI Citation database and Medline. SETTING: General practice. SUBJECTS: Sixty-one articles (54 studies). MEASURES: The articles were assessed according to the following design variables: setting; definition of FAs; sampling; sample size; control groups; study aim; study design; data sources; effect measure; and main results. RESULTS: There was no generally accepted definition of frequent attendance. Research designs differed substantially. Eight articles gave sufficient information on all design variables. The top 10% of attenders accounted for 30-50% of all contacts, and up to 40% of FAs were still FAs the following year. More than 50% of FAs had a physical disease, more than 50% of FAs suffered from psychological distress, social factors (low social support, unemployment, divorce) were associated with frequent attendance in more than 50% of FAs, multiproblems (physical, psychological and social) were found in one-third of FAs, and frequent attendance was associated with increasing age and female gender. CONCLUSION: The diversity of designs, definitions and methods in the current literature on FAs in general practice hampers comparison of their precision, validity and generalizability, and calls for cautious interpretation and adoption of a common, generally acceptable definition in future studies.     

HIV prevention, cost-utility analysis, and race/ethnicity: methodological considerations and recommendations.

In this methodological article, the author reviews 1) the disproportionate impact that HIV/AIDS is having on communities of color in the United States, 2) what is known about the cost-effectiveness of HIV prevention interventions for racial/ethnic minority communities (including the methods used in these studies), and 3) the relative lack of methodological guidance in the field for conducting economic evaluation studies specifically for communities of color. The author finds that race/ethnicity affects cost-utility analyses in several heretofore unrecognized ways. In this article, methodological techniques to address these concerns are proposed. In particular, the author recommends cost-utility analytic strategies that maximize comparability among studies and avoid the introduction of methodological discrimination.     

Drinking water infrastructure and environmental disparities: evidence and methodological considerations

Potable drinking water is essential to public health; however, few studies have investigated income or racial disparities in water infrastructure or drinking water quality. There were many case reports documenting a lack of piped water or serious water quality problems in low income and minority communities, including tribal lands, Alaskan Native villages, colonias along the United States-Mexico border, and small communities in agricultural areas. Only 3 studies compared the demographic characteristics of communities by the quality of their drinking water, and the results were mixed in these studies. Further assessments were hampered by difficulties linking specific water systems to the sociodemographic characteristics of communities, as well as little information about how well water systems operated and the effectiveness of governmental oversight.     

The remediation challenge: theoretical and methodological insights from a systematic review

Objectives Remediation is usually offered to medical students and doctors in training who underperform on written or clinical examinations. However, there is uncertainty and conflicting evidence about the effectiveness of remediation. The aim of this systematic review was to synthesise the available evidence to clarify how and why remediation interventions may have worked in order to progress knowledge on this topic. Methods The MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), ERIC (Educational Resources Information Centre), Web of Science and Scopus databases were searched for papers published from 1984 to April 2012, using the search terms ‘remedial teaching’, ‘education’, ‘medical’, ‘undergraduate’/or ‘clinical clerkship’/or ‘internship and residency’, ‘at risk’ and ‘struggling’. Only studies that included an intervention, then provided retest data, and reported at least one outcome measure of satisfaction, knowledge, skills or effects on patients were eligible for inclusion. Studies of practising doctors were excluded. Data were abstracted independently in duplicate for all items. Coding differences were resolved through discussion. Results Thirty‐one of 2113 studies met the review criteria. Most studies were published after 2000 (n = 24, of which 12 were published from 2009 onwards), targeted medical students (n = 22) and were designed to improve performance on an immediately subsequent examination (n = 22). Control or comparison groups, conceptual frameworks, adequate sample sizes and long‐term follow‐up measures were rare. In studies that included long‐term follow‐up, improvements were not sustained. Intervention designs tended to be highly complex, but their design or reporting did not enable the identification of the active components of the remedial process. Conclusions Most remediation interventions in medical education focus on improving performance to pass a re‐sit of an examination or assessment and provide no insight into what types of extra support work, or how much extra teaching is critical, in terms of developing learning. More recent studies are generally of better quality. Rigorous approaches to developing and evaluating remediation interventions are required.     

A link between chronic sleep restriction and obesity: methodological considerations

Emerging evidence suggests that chronic sleep restriction contributes to obesity. Targeting short sleep duration may therefore offer a novel and effective method of preventing and treating obesity. However, this area of research is only in its infancy, and a complete understanding of how chronic sleep restriction and obesity are linked is currently lacking. The aim of this paper is to briefly review epidemiological evidence for an association between chronic sleep restriction and obesity in adults, and outline the key methodological limitations of these studies. Particular attention is paid to the methods used to measure sleep and obesity, as well as the need to control for potential confounding variables. Methodological recommendations are provided for future studies that will facilitate a more complete understanding of how chronic sleep restriction and obesity are linked in the general population. This has implications for the development of public health programmes that target sleep as a modifiable risk factor for obesity.     

The effects of hormonal contraceptives on lactation: current findings, methodological considerations, and future priorities

Findings and shortcomings of several articles which review clinical studies of lactation are discussed, and the main recommendations for family planning programs that have emerged from them are summarized. The basic recommendation has been that hormonal preparations containing estrogen should be avoided during either the early or the entire period of lactation. The largest number of studies have considered milk yield and establishment and maintenance of lactation; aspects of these studies discussed in this article include cultural and social factors; sample characteristics and size; use of control groups, placebos, and double blind design; the hormone preparations used; timing of hormone administration; duration of treatment and observation; indicator of milk yield; basis for comparison and analytical measures; and other influences. Despite the number and diversity of variables involved and the pitfalls in studying them, the balance of evidence appears to support the conclusion that preparations containing estrogen are more often implicated in suppression of lactation than are progestogen-only preparations. Most reviews which consider milk quality conclude that evidence is conflicting but that any adverse affects are trivial, although the need for further research is noted, particularly concerning the effects of possible changes in milk composition on the infant. Very little research has been reported on the transfer of steroids to the infant via breastmilk. Future research should include thorough evaluation of existing studies; further research into physiological aspects of lactation and hormonal contraception; review of existing data on lactation problems from family planning programs; and clinical studies that correct or avoid the methodological shortcomings of earlier research.     

A research programme in lifestyle and health: methodological and theoretical considerations

Traditionally, research in health behaviour has been dominated by research ideologies and methods which developed in the health sciences and the social sciences. To a great extent these subjects have followed "classical" research designs propounded by the natural sciences. The result has been a marked dependency on survey research, quasi-experimental designs, case-control studies and other "static" designs. This research has been characterised by brief periods of intensive "data-collection", followed by long periods of analysis and report writing. These research endeavours often constitute an extensive, elaborate, and usually accurate picture of health attitudes, opinions and behaviours at the point of data collection. But they are simply "snapshots" of a group, culture, nation, etc. at one moment in time. This research is not "dynamic" and it is not surprising that despite the considerable amount of health behaviour research which exists, we still know relatively little about the process and dynamics of health behaviour change. Fortunately there is increasing concern, both theoretical and methodological, with the problem of behavioural change over time. On balance, the theoretical arguments are not well developed, however the methodological techniques for exploring continuous data are becoming available. This paper presents one model for an emerging research programme in lifestyle and health which attempts to address some of the theoretical and methodological issues discussed.     

COVID-19 mRNA vaccines as hypothetical epigenetic players: Results from an in silico analysis,considerations and perspectives

ObjectivesTo investigate in silico the occurrence of epigenetic crosstalk by nucleotide sequence complementarity between the BNT162b2 mRNA vaccine and whole human genome, including coding and noncoding (nc)RNA genes. To correlate these results with those obtained with the original spike (S) gene of Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2).MethodsThe publicly available FASTA sequence of the BNT162b2 mRNA vaccine and the SARS-CoV-2 isolate Wuhan-Hu-1 S gene (NC_045512.2) were used separately as key input to the Ensembl.org library to evaluate base pair match to human GRCh38 genome. Human coding and noncoding genes harboring hits were assessed for functional activity and health effects using bioinformatics tools and GWAS databases.ResultsThe BLAT analysis against the human GRCh38 genome revealed a total of 37 hits for BNT162b2 mRNA and no hits for the SARS-CoV-2 S gene. More specifically, BNT162b2 mRNA matched 19 human genes whose protein products are variously involved in enzyme reactions, nucleotide or cation binding, signaling, and carrier functions.In BLASTN analysis of ncRNA genes, BNT162b2 mRNA and SARS-CoV-2 S gene matched 17 and 24 different human genomic regions, respectively. Overall, characterization of the matched noncoding sequences revealed stronger interference with epigenetic pathways for BNT162b2 mRNA compared with the original S gene.ConclusionThis pivotal in silico analysis shows that SARS-CoV-2 S gene and the BNT162b2 mRNA vaccine exhibit Watson-Crick nucleotide complementarity with human coding or noncoding genes. Although they do not share the same complementarity pattern, both may disrupt epigenetic mechanisms in target cells, potentially leading to long-term complications.     

Current issues in testing,selection and use of microbicides in infection control: a critical review

Infectious diseases remain a major threat to human health and, indeed, many aspects of modern life are increasing our vulnerability and exposure to a variety of frank and opportunistic pathogens. This, together with rampant antibiotic resistance and reduced prospects for new therapies and vaccines, is increasing our reliance on microbicides as a part of preventive strategies. However, a closer scrutiny of microbicide use reveals flaws in ’official’ methods for product registration, validity of label claims of microbicidal activity as well as short- and long-term health and environmental safety of many chemicals widely used for the purpose.This review is a critical look at these issues, with particular emphasis on microbicides used for environmental surface and medical device disinfection in healthcare settings. It summarises current approaches to developing better ways of testing microbicides and to attain global harmonisation of testing and product registration. It also highlights the known and potential dangers of microbicide use in the workplace and the factors to consider in the selection and application of such formulations to optimise safety and effectiveness in the field.A better awareness of the general safety issues must precede any continued reliance on microbicides in infection control. The information herein should help: infection control committees in their training, education and advisory services; materials managers in the purchase of suitable and safe products; infection control practitioners in microbicide use for enhanced workplace, patient and environmental safety; manufacturers in designing safer products and in making their labels more user-friendly, and; regulators in updating and refining the process of registration of microbicides. With the increasing reliance on microbicides in infection control, well-informed end-users are crucial to ensure that chemicals used for the purpose are handled as effectively and safely as possible.