Breaking new ground: challenging existing asthma guidelines

Background

While we have international guidelines and various national guidelines for asthma diagnosis and management, asthma remains poorly controlled in many children and adults. In this paper we review the limitations of current asthma guidelines and describe important issues and remaining questions regarding asthma guidelines for use, particularly in primary care.

Discussion

Clinical practice guidelines based on evidence from randomized controlled trials are considered the most rigorous and accurate. Current evidence-based guidelines are written predominantly from the perspective of the patient with a clear-cut asthma diagnosis, however, and tend not to consider the heterogeneity of asthma or to accommodate individual patient variations in response to treatment or their needs, differences in practice settings, or local differences in availability and cost of therapies. The results of randomized controlled trials, which are designed to establish efficacy of treatment under ideal conditions, may not apply to 'real-world' clinical practice, where patients are unselected, monitoring is less frequent, and effectiveness – the benefit of treatment in routine clinical practice – is the most relevant outcome. Moreover, most guidelines see asthma in isolation rather than considering other factors that may impact on asthma and response to asthma therapy, particularly age, allergic rhinitis, cigarette smoking, adherence, and genetic factors. When these links are recognized, guidelines rarely provide practical recommendations for treatment in these scenarios. Finally, there is some evidence that general practitioners are not convinced of the applicability of asthma guidelines to their practice settings, especially when those writing the guidelines principally work in specialist practice.

Conclusion

Developing country-specific guidelines or, ideally, local guidelines could provide more practical solutions for asthma care and could account for regional factors that influence patient choice and adherence to therapy. Pragmatic clinical trials and well-designed observational trials are needed in addition to randomized controlled trials to assess real-world effectiveness of therapies, and such evidence needs also to be considered by guideline writers. Finally, practical tools to facilitate the diagnosis and assessment of asthma and factors responsible for poor control, such as associated allergic rhinitis, limited adherence, and smoking behavior, are needed to supplement treatment information provided in clinical practice guidelines for asthma.

     

Molecular pathways in aseptic loosening of orthopaedic endoprosthesis

Operative joint replacement to treat disabling joint conditions secondary to degenerative and inflammatory arthritides has become one of the most efficacious and cost-effective procedures to relieve pain and restore joint function. However, prosthetic implants are not built to last forever and osteolysis and aseptic loosening has been associated with prosthetic arthroplasties since their introduction. The functional life of a synthetic joint is influenced by many factors including the material of the implant, operation procedures and the surgeon involved, as well as patient-related factors. Although promising developments have been achieved in this field, more than 10% of all implants still have to undergo operative revision within 15 years after the initial operation. Failure due to sepsis, fractures and dislocations has become rare; premature loosening of implants on the other hand is becoming much more important. Prosthetic loosening without concurrent infection or trauma is called aseptic loosening. It is generally accepted that small particles ("wear debris") and activated macrophages play a key role in aseptic loosening. The pathophysiology of this condition, however, is still not very well characterized. In this article, we review the molecular mechanisms and signal pathways that were unravelled as responsible factors for loosening orthopaedic implants. Finally, we discuss possible novel strategies for future therapeutic approaches.     

Strength requirements for internal and external prostheses

Throughout the history of development of joint replacement implants and external prostheses there have been mechanical failures due to a discrepancy between material strength, cross-sectional characteristics and the loads developed in normal or abnormal function by the patient utilising the device. Particularly for internal prostheses attention is being paid at the present time to wear characteristics and the requirements for the articulating surfaces and the volume of wear particles produced during tests simulating the use of the device within the patient. The particular importance of the wear particles is that they seem to be associated with accelerated resorption of bone at areas essential for successful fixation of the implant within it. This article will consider joint replacements at the knee and hip and external prostheses for the leg. If failure due to external trauma is ignored the loads to be considered in testing standards correspond in implants to the muscular and ligamentous forces related to the forces developed between ground and foot and to the bending moments in the structure of leg prostheses. Generally it can be assumed that the treatment of the patient following trauma is more easily accomplished and more likely to be successful if the prosthesis has failed and not the bony structure of the patient. However, the author is unaware that these devices have ever been designed to have lower intrinsic strength than the anatomical structures to which they are connected; indeed in many cases particularly for implants they are much stronger than the bone to which they are connected. The major difficulty in rational design of prosthetic devices has been uncertainty about the importance of occasionally applied loads of a high value relative to those on a frequent basis and also to the frequency of application of these overloads. In this paper consideration is given to methods of determination of load systems relevant to the mechanical performance of implanted joint replacements at the hip and the knee and external prostheses for leg amputees. New data are presented relating to walking, other daily activities and the corresponding frequency of occurrence of these. Loading data on implants obtained by various biomechanical models is compared and related to the loads actually measured by implanted transducers. The philosophy of the standardised test load systems and the performance requirements is reviewed.     

Effect of 6-methoxybenzoxazolinone on sex ratio and breeding performance in Microtus montanus

The plant derivative, 6-mathoxybenzoxazolinone (6-MBOA), which has been demonstrated to initiate reproduction in field populations of the montane meadow vole (Microtus montanus), was administered via feeding or Silastic capsule implants to mated pairs of laboratory bred M. montanus. The animals remained paired for 120 days, and the number, size, and sex ratios of the resulting litters were recorded. Both the size and frequency of litters were significantly greater in 6-MBOA-treated pairs than in controls. By using implants, it was possible to treat one or both sexes in a mated pair. The positive effects of this compound on litter size and number of litters occurred when the females received implants, which indicates that the male has no influence on these parameters. The most unusual result of these experiments was that 6-MBOA has a significant effect on the sex ratio of the litters. Animals receiving 6-MBOA produced significantly more females than did control pairs. This result occurred regardless of the method of administration, and in the case of the implant studies, regardless of which sex received the active implants. These findings are discussed in relation to the ecology and life history strategy of Microtus montanus.     

Intensive care triage: priority should be independent of whether patients are already receiving intensive care

Intensive care units (ICUs) are not always able to admit all patients who would benefit from intensive care. Pressure on ICU beds is likely to be particularly high during times of epidemics such as might arise in the case of swine influenza. In making choices as to which patients to admit, the key US guidelines state that significant priority should be given to the interests of patients who are already in the ICU over the interests of patients who would benefit from intensive care but who have not been admitted. We examine four reasons that in principle might justify such a prioritization rule and conclude that none is convincing. We argue that the current location of patients should not, in principle, affect their priority for intensive care. We show, however, that under some but not all circumstances, maximizing lives saved by intensive care might require continuing to treat in the ICU a patient already admitted rather than transferring that patient out of the unit in order to admit a sicker patient who would also benefit more from intensive care. We conclude that further modelling is required in order to clarify what practical policies would maximize lives saved by intensive care.     

Potassium iodide (KI) to block the thyroid from exposure to I-131: current questions and answers to be discussed

Thyroid cancer in children and adolescents has to be considered as the most severe health consequence of a nuclear reactor emergency with release of radioiodine into the atmosphere. High doses of potassium iodide are effective to block radioiodine thyroid uptake and to prevent development of thyroid cancer years later. However, there are controversies concerning thyroid cancer risk induced by radioiodine exposure in adults. Further, the interaction of nutritional supply of potassium iodide and radioiodine uptake as well as the interaction of radioiodine with certain drugs has not been addressed properly in existing guidelines and recommendations. How to proceed in case of repeated release of radioiodine is an open, very important question which came up again recently during the Fukushima accident. Lastly, the side effects of iodine thyroid blocking and alternatives of this procedure have not been addressed systematically up to now in guidelines and recommendations. These questions can be answered as follows: in adults, the risk to develop thyroid cancer is negligible. In countries, where nutritional iodine deficiency is still an issue, the risk to develop thyroid cancer after a nuclear reactor emergency has to be considered higher because the thyroid takes up more radioiodine as in the replete condition. Similarly, in patients suffering from thyrotoxicosis, hypothyroidism or endemic goitre not being adequately treated radioiodine uptake is higher than in healthy people. In case of repeated or continued radioiodine release, more than one dose of potassium iodide may be necessary and be taken up to 1 week. Repeated iodine thyroid blocking obviously is not harmful. Side effects of iodine thyroid blocking should not be overestimated; there is little evidence for adverse effects in adults. Newborns and babies, however, may be more sensitive to side effects. In the rare case of iodine hypersensitivity, potassium perchlorate may be applied as an alternative to iodine for thyroid blocking.     

The unknown risk of vertical transmission in sleeping sickness--a literature review

Background

Children with human African trypanosomiasis (HAT) present with a range of generally non-specific symptoms. Late diagnosis is frequent with often tragic outcomes. Trypanosomes can infect the foetus by crossing the placenta. Unequivocal cases of congenital infection that have been reported include newborn babies of infected mothers who were diagnosed with HAT in the first 5 days of life and children of infected mothers who had never entered an endemic country themselves.

Methods

This review systematically summarizes the literature on the vertical transmission of HAT, to our knowledge for the first time. To approach the broader aspects of the subject, articles considering the epidemiology of childhood HAT and HAT in pregnancy were also included. The HAT guidelines and technical reports of the World Health Organisation, Médecins Sans Frontières, Institut de Recherche pour le Développement, and of one endemic country were reviewed.

Results

Publications describing congenital HAT are very limited and consist only of single case reports and small case series. Generally it is assumed to be a rare event, but it has never been systematically investigated. In two publications, it is hypothesized that congenital HAT occurs more often than suspected. Not all guidelines and not all HAT literature mention this transmission route.

Conclusions

The risk of vertical transmission is unknown. Awareness of congenital HAT is insufficient, and as a result opportunities for an early diagnosis in newborns may be missed. All HAT guidelines and local HAT protocols should stress that in endemic areas pregnant women should be systematically checked for HAT and that newborns of HAT infected mothers should be assessed for the disease as soon as possible. Studies on the impact of HAT on fertility and pregnancy and studies on congenital HAT are long overdue.     

Decision analysis of prenatal testing for chromosomal disorders: what do the preferences of pregnant women tell us?

Current guidelines recommend offering invasive testing for chromosomal disorders only to women who are aged 35 or older, or who are at similarly elevated risk (as determined by maternal serum and/or ultrasonographic screening). We conducted a decision analysis, using preference scores obtained from pregnant women, to determine whether current guidelines maximize the health-related quality of life of these women. If only miscarriage and chromosomal abnormalities are considered, the expected value of testing exceeds that of not testing for women 30 years of age or older. However, if a comprehensive range of relevant testing outcomes is considered, testing offers a higher expected value than not testing, regardless of age. Furthermore, patient preferences for specific testing outcomes play a much more substantial role in determining the course of action with the highest expected value than does the probability of any of the possible testing outcomes. The current age- and risk-based guideline for prenatal diagnosis does not maximize expected value and fails to appropriately consider individual patient preferences. For counseling purposes, how an individual values the presence and timing of fetal chromosomal information should be carefully understood.     

Interaction of radio frequency electromagnetic fields and passive metallic implants--a brief review

During the last decade, use of radio frequency (RF) applications like mobile phones and other wireless devices, has increased remarkably. This has triggered numerous studies related to possible health risks due to the exposure of RF electromagnetic (EM) fields. One safety aspect is the coupling of EM fields with active and passive implants in the human body. While interactions with active implants have been quite extensively researched, only a few studies have focused on passive implants. The present article reviews interaction mechanisms and studies of passive metallic, that is, conductive, implants in common external RF EM fields. It is found that implants have been mostly studied numerically, and experimental studies are rare. Furthermore, the studies cover mostly far-field conditions and only a few have studied implants in near fields. A summary of results indicates that a conductive object in tissues may cause notable local enhancement of the EM field and thus enhanced power absorption. The degree of enhancement depends, for example, on the orientation, the dimensions, the shape, and the location of the implant. However, in most of the cases, the field enhancement has not been strong enough to cause remarkable excess heating (more than 1 degrees C) of tissues.     

An Italian tomato “Cuore di Bue” case study: challenges and benefits using subcategory assessment method for social life cycle assessment

Purpose

The main purpose of this study is to present an implementation of the subcategory assessment method (SAM) to the life cycle of an Italian variety of tomato called “Cuore di Bue” produced by an Italian cooperative. The case study was used to use the methodology proposed in compliance with the guidelines of social life cycle assessment (S-LCA) in order to highlight issues for the improvement of SAM. A summary of strengths and weaknesses of the methodology as well as the social performance of the considered Italian tomato is an important result of this case study.

Methods

The methodology used is based on SAM. The UNEP/SETAC guidelines of S-LCA and the complementary methodological sheets were used as main references to carry out SAM, and it was used to assess the social performances of Cuore di Bue. The focus was on the assessment of the following three out of five stakeholder groups presented in the guidelines: workers, local community and consumers. Specific questionnaires have been developed to collect the inventory data related to each stakeholder group and along the product life cycle.

Results and discussion

SAM of Cuore di Bue showed a range of values, between 2 and 3 (C-B) for consumer stakeholder group and mainly 3 (B) for the local community and worker stakeholders. Because the best performance (A) is related to a numerical value of 4, better performances were not identified, owing to no propagation of actions in the value chain. The collective bargaining, transparency, feedback mechanism and privacy are the subcategories with the worst performance, but at the same time with more potential for improvements.

Conclusions

The implementation of SAM on Cuore di Bue allowed us to demonstrate how SAM transforms qualitative data into semi-quantitative information through a score scale that can help a decision maker achieve a product overview. SAM has been implemented on Cuore di Bue; the product assessment, the strengths and weaknesses of the methodology are identified and discussed as well. It has been possible to present the best and worst performances in product life cycle, by identifying the phase or the subcategories with good or bad performance. However, in this case study, as the same company owns most of the product life cycle taken into account, the majority of social performances are identical, and this may represent a limit of the methodology or that more organisations along the life cycle must be taken into account (for example, energy, distribution).

     

Implementation of Mental Health Service Has an Impact on Retention in HIV Care: A Nested Case-Control Study in a Japanese HIV Care Facility

Background

Poor retention in the care of patients with human immunodeficiency virus (HIV) is associated with adverse patient outcomes such as antiretroviral therapy failure and death. Therefore, appropriate case management is required for better patient retention; however, which intervention in case management is important has not been fully investigated. Meanwhile, in Japan, each local government is required to organize mental health services for patients with HIV so that a case manager at an HIV care facility can utilize them, but little is known about the association between implementation of the services and loss to follow-up. Therefore, we investigated that by a nested case-control study.

Methods

The target population consisted of all patients with HIV who visited Osaka National Hospital, the largest HIV care facility in western Japan, between 2000 and 2010. Loss to follow-up was defined as not returning for follow-up care more than 1 year after the last visit. Independent variables included patient demographics, characteristics of the disease and treatment, and whether the patients have received mental health services. For each case, three controls were randomly selected and matched.

Results

Of the 1620 eligible patients, 88 loss to follow-up cases were identified and 264 controls were matched. Multivariate-adjusted conditional logistic regression revealed that loss to follow-up was less frequent among patients who had received mental health services implemented by their case managers (adjusted odds ratio [95% confidence interval] 0.35 [0.16-0.76]). Loss to follow-up also occurred more frequently in patients who did not receive antiretroviral therapy (adjusted odds ratio [95% confidence interval], 7.51 [3.34-16.9]), who were under 30 years old (2.74 [1.36-5.50]), or who were without jobs (3.38 [1.58-7.23]).

Conclusion

Mental health service implementation by case managers has a significant impact on patient retention.     

Soft and hard tissue response to zirconium dioxide dental implants--a clinical study in man

Titanium dental implants have been used successfully in implantology for more than 40 years. Recent research, however, suggests that titanium might have more side effects than previously believed. Zirconia ceramics have been employed in orthopaedic surgery for approximately 30 years and were recently introduced into dentistry as a metal replacement for crown and bridge work as well as implant abutments. Zirconium dioxide has been shown in both in vitro and in vivo studies to have desirable osseointegrative properties. This clinical study shows that dental implants made from zirconia are a feasible alternative to titanium dental implants. In addition to excellent cosmetic results, zirconia implants allow a degree of osseointegration and soft tissue response that is superior to titanium dental implants.     

RHEUMATOID ARTHRITIS—Diagnosis in Peripheral Joint Affliction

The diagnosis of rheumatoid arthritis in a typical case depends upon a history of pain and swelling of various joints throughout the body. In the first stages the disease usually involves only the small joints of the hands and feet, but sooner or later it spreads to the larger joints. This may be accompanied by fibrosis of one or more joints, causing disability ranging from disuse of one joint up to total incapacity. Diagnosis in early or atypical cases is often impossible until the patient has been under observation a long time. It is important that diagnosis be made as early as possible, in order that appropriate therapy may be started and ankylosis and disability of the joints prevented.Since laboratory procedures and roentgen films do not show early changes, emphasis is placed on the history and physical examination for diagnosis.     

Rheumatoid arthritis; diagnosis in peripheral joint affliction

The diagnosis of rheumatoid arthritis in a typical case depends upon a history of pain and swelling of various joints throughout the body. In the first stages the disease usually involves only the small joints of the hands and feet, but sooner or later it spreads to the larger joints. This may be accompanied by fibrosis of one or more joints, causing disability ranging from disuse of one joint up to total incapacity. Diagnosis in early or atypical cases is often impossible until the patient has been under observation a long time. It is important that diagnosis be made as early as possible, in order that appropriate therapy may be started and ankylosis and disability of the joints prevented. Since laboratory procedures and roentgen films do not show early changes, emphasis is placed on the history and physical examination for diagnosis.     

Growth of bones as revealed by implant markers in animals

Implantation of screws, pegs, wires, or other material as markers has been of value during the last 200 years in the serial study of growth of bones. With this direct method, for a given period, the increase in distance between implants on either side of an endochondral growth center or suture can be readily determined. In contrast, the relatively constant position of two or more implants within a single bone can be utilized to establish the pattern of peripheral apposition and resorption. When radiopaque implants are used in combination with serial roentgenography, not only the amount but also the rate, periods of activity and relative direction of growth may be determined. This indirect method obviates reoperating or killing the animal to measure the distance between implants. Some of the problems in the use of these methods are that (1) growth occurs in more than one plane, (2) the implants may not remain where inserted into the bone, (3) the implants may not be in a plane parallel to the X -ray film, and (4) the distance between the implants and the film may not be constant. (Abstract previously published Am. J. Phys. Anthrop., 27: 236, September, 1967).     

Osteonecrosis of the jaw developing during bisphosphonate treatment

The article discusses osteonecrosis of the jaw as a possible side effect of bisphosphonate treatment. It provides practical guidelines for prevention, diagnosis and management of bisphosphonate-associated osteonecrosis according to literature and clinical evidence. Since controlled clinical trials have not been carried out, the recommendations are based on reviews, reports and clinical experience. Osteonecrosis of the jaw (ONJ) is a historical clinical entity, which can potentially develop in cancer patients receiving bisphosphonate therapy. The pathogenesis of ONJ has not been totally revealed yet. A thorough dental/oral surgical examination and counseling is recommended in cases when intravenous bisphosphonate therapy is needed. All required dental and surgical treatment should be carried out before starting bisphosphonate therapy to prevent ONJ. The patient should be informed about the possible side effects, and the importance of good oral home care and regular dental check-ups. Once the intravenous bisphosphonate therapy has started, only conservative manipulations should be carried out in the oral cavity. Even in case of developed ONJ, suspension of bisphosphonate therapy is not necessary. In these cases a non-surgical approach is recommended concerning the treatment of ONJ. Regarding the growing number of ONJ cases in association with bisphosphonate therapy it is important for the professionals treating cancer patients to be aware of this phenomenon and the importance of prevention.     

Staged use of soft-tissue expansion and lower thoracic advancement flap in breast reconstruction

A single patient is presented in whom breast reconstruction after mastectomy for breast cancer has been achieved by sequential use of soft-tissue expansion followed by permanent silicone implant placement and thoracic flap advancement to define the inframammary fold. This procedure may play a useful role in patients in whom other, more complex methods of breast reconstruction are not selected or indicated and in particular in patients in whom bilateral silicone implants are utilized.     

Present clinical applications of osseointegrated percutaneous implants

Altogether, 389 screws of commercially pure titanium have been inserted at various locations in the facial skeleton of 174 patients. The indications for treatment have been stable anchorage of an external hearing aid or a facial episthesis, in the latter case to restore the facial contours after congenital disorders or status after trauma or cancer surgery. All implants have been inserted in a two-stage procedure, the first being anchorage of the titanium elements in the bone, the second, minimally 3 months later, being establishment of a permanent skin penetration. The outcome of every inserted implant has been analyzed. Only six implants failed to become integrated in bone and had to be removed. Five of these failures occurred in previously irradiated bone, where the success rate was estimated to 85.3 percent. In nonirradiated bone, 354 of 355 inserted implants became osseointegrated, i.e., anchored in bone in a stable manner. The soft tissues were without any adverse reactions in 92 percent of the 951 clinical observations, whereas potentially serious skin complications were observed in only 2.8 percent. Presently, the longest clinical follow-up is 8 years, and 37 implants have been followed for more than 5 years. We believe that this clinical material is the first in which an uneventful bone anchorage and skin penetration have been demonstrated in consecutively operated upon clinical cases. The implants used for anchoring an external hearing aid were also successful in the sense that the patients gained 15 dB (average) in hearing threshold and showed a significantly improved discrimination score. The implants inserted to hold facial epistheses resulted in considerably improved retention and a good cosmetic outcome for the patients.     

New generation water quality guidelines for ecosystem protection

1. Water quality guidelines are important for the management of water resources. Initially, guidelines focused on quality for domestic drinking water and for agricultural, recreational and industrial purposes. More recently, the emphasis has been on ecosystem protection, as well. 2. This paper discusses the key elements of new risk-based water quality guidelines being developed in Australia and New Zealand, that should lead to more effective management and protection of aquatic ecosystems. 3. There are three essential elements to this new approach: (i) it is ecosystem-based— ideally the guidelines should be, as far as possible, ecosystem-specific; (ii) it is issue-based— the guidelines should focus on the actual issues or problems caused by physical, chemical and biological stressors rather than on the individual indicators, as at present; and (iii) it is risk-based. There is generally great difficulty in deciding whether adverse biological effects will result from various stressors added to an ecosystem. The new approach develops guideline ‘packages’ for each issue and, where possible, for each ecosystem type. Each ‘package’ consists of specified key performance indicators, trigger levels for these indicators (that is, levels which indicate the degree of risk that adverse biological effects may occur), and for high risk situations (where trigger levels are exceeded) a protocol for considering the effect of ecosystem-specific factors in reducing (or enhancing) the biological effects. 4. This paper presents a case study related to a highly relevant aquatic ecosystem issue in Australia, namely the excessive growth of cyanobacteria (blue-green algal blooms), to illustrate how the new risk-based guidelines might be applied.     

Evaluating the Evidence for Hormesis: A Statistical Perspective

It is possible to account for hormesis under current regulatory guidelines by invoking criteria for departure from default risk assessment procedures. However, past experience suggests that it will be difficult to amass enough evidence for hormesis in an individual case to permit departure from default procedures. Accordingly, hormesis is likely to be important in agency risk assessments only if guidelines are modified to incorporate hormesis as a default assumption. This could be appropriate if hormesis is determined to be a universal or near-universal phenomenon. Although there is ample evidence that hormesis occurs in many specific situations, the overall prevalence of hormesis is very difficult to evaluate based on currently available data. The lack of a valid statistical test for hormesis is a major limitation when evaluating evidence for hormesis. The attempts at estimating the prevalence of hormesis reviewed herein did not adequately control for false positives and/or may have had inadequate power to detect hormesis. Some suggestions are made for constructing a database and analyzing the data therein that would provide more readily interpretable information on the prevalence of hormesis.