Challenges of Loss to Follow-up in Tuberculosis Research.

In studies evaluating methods for diagnosing tuberculosis (TB), follow-up to verify the presence or absence of active TB is crucial and high dropout rates may significantly affect the validity of the results. In a study assessing the diagnostic performance of the QuantiFERON®-TB Gold In-Tube test in TB suspect children in Tanzania, factors influencing patient adherence to attend follow-up examinations and reasons for not attending were examined. In 160 children who attended and 102 children who did not attend scheduled 2-month follow-up baseline health characteristics, demographic data and risk factors for not attending follow-up were determined. Qualitative interviews were used to understand patient and caretakers reasons for not returning for scheduled follow-up. Being treated for active tb in the dots program (OR: 4.14; 95% CI:1.99-8.62;p-value<0.001) and receiving money for the bus fare (OR:129; 95% CI 16->100;P-value<0.001) were positive predictors for attending follow-up at 2 months, and 21/85(25%) of children not attending scheduled follow-up had died. Interviews revealed that limited financial resources, i.e. lack of money for transportation and poor communication, were related to non-adherence. Patients lost to follow-up is a potential problem for TB research. Receiving money for transportation to the hospital and communication is crucial for adherence to follow-up conducted at a study facility. Strategies to ensure follow-up should be part of any study protocol

Techniques for Arbuscular Mycorrhiza Inoculum Reduction

It is well established that arbuscular mycorrhizal (AM) fungi can play a significant role in sustainable crop production and environmental conservation. With the increasing awareness of the ecological significance of mycorrhizas and their diversity, research needs to be directed away from simple records of their occurrence or casual speculation of their function (Smith and Read 1997). Rather, the need is for empirical studies and investigations of the quantitative aspects of the distribution of different types and their contribution to the function of ecosystems. There is no such thing as a fungal effect or a plant effect, but there is an interaction between both symbionts. This results from the AM fungi and plant community size and structure, soil and climatic conditions, and the interplay between all these factors (Kahiluoto et al. 2000). Consequently, it is readily understood that it is the problems associated with methodology that limit our understanding of the functioning and effects of AM fungi within field communities. Given the ubiquous presence of AM fungi, a major constraint to the evaluation of the activity of AM colonisation has been the need to account for the indigenous soil native inoculum. This has to be controlled (i.e. reduced or eliminated) if we are to obtain a true control treatment for analysis of arbuscular mycorrhizas in natural substrates. There are various procedures possible for achieving such an objective, and the purpose of this chapter is to provide details of a number of techniques and present some evaluation of their advantages and disadvantages. Although there have been a large number of experiments to investigated the effectiveness of different sterilization procedures for reducing pathogenic soil fungi, little information is available on their impact on beneficial organisms such as AM fungi. Furthermore, some of the techniques have been shown to affect physical and chemical soil characteristics as well as eliminate soil microorganisms that can interfere with the development of mycorrhizas, and this creates difficulties in the interpretation of results simply in terms of possible mycorrhizal activity. An important subject is the differentiation of methods that involve sterilization from those focussed on indigenous inoculum reduction. Soil sterilization aims to destroy or eliminate microbial cells while maintaining the existing chemical and physical characteristics of the soil (Wolf and Skipper 1994). Consequently, it is often used for experiments focussed on specific AM fungi, or to establish a negative control in some other types of study. In contrast, the purpose of inoculum reduction techniques is to create a perturbation that will interfere with mycorrhizal formation, although not necessarily eliminating any component group within the inoculum. Such an approach allows the establishment of different degrees of mycorrhizal formation between treatments and the study of relative effects. Frequently the basic techniques used to achieve complete sterilization or just an inoculum reduction may be similar but the desired outcome is accomplished by adjustments of the dosage or intensity of the treatment. The ultimate choice of methodology for establishing an adequate non-mycorrhizal control depends on the design of the particular experiments, the facilities available and the amount of soil requiring treatment

What are the psychosocial outcomes of treatment for thyroid eye disease? A systematic review

Background: Thyroid eye disease (TED) causes a number of esthetic and visual problems and its treatment requires close clinical assessment, often for several years. There is evidence to suggest that clinical factors are poor indicators of patient-reported outcomes after treatments that aim to improve appearance, vision, or both. Psychosocial factors can impact on both adjustment to living with TED and also patients’ perceptions of their improvements after treatment. There has been growing recognition that it is essential to evaluate treatment efficacy in terms of psychosocial outcomes but, to date, there has been no review that has systematically evaluated psychosocial outcomes following a variety of treatments for TED. Summary: Fifteen studies were included in the review and 6 were randomized controlled trials (RCTs). The studies varied greatly in methodological rigor; whilst major treatments such as surgery do improve quality of life outcomes, other non-invasive treatments such as intravenous steroids can have a similar impact and show long-term benefits. Only 3 studies reviewed orbital decompressive surgery which showed better psychosocial outcomes than other types of surgery. Conclusions: The effect of some treatments remains unclear due to poor methodology and poor reporting of results. Clinicians need to be aware when planning rehabilitative treatments such as surgery the influence of psychosocial factors on quality of life outcomes and the lack of a relationship with clinical factors such as disease severity

The implausibility of ‘usual care’ in an open system: sedation and weaning practices in Paediatric Intensive Care Units (PICUs) in the United Kingdom (UK)

Background: The power of the randomised controlled trial depends upon its capacity to operate in a closed system whereby the intervention is the only causal force acting upon the experimental group and absent in the control group, permitting a valid assessment of intervention efficacy. Conversely, clinical arenas are open systems where factors relating to context, resources, interpretation and actions of individuals will affect implementation and effectiveness of interventions. Consequently, the comparator (usual care) can be difficult to define and variable in multi-centre trials. Hence outcomes cannot be understood without considering usual care and factors that may affect implementation and impact on the intervention. Methods: Using a fieldwork approach, we describe PICU context, ‘usual’ practice in sedation and weaning from mechanical ventilation, and factors affecting implementation prior to designing a trial involving a sedation and ventilation weaning intervention. We collected data from 23 UK PICUs between June and November 2014 using observation, individual and multi-disciplinary group interviews with staff. Results: Pain and sedation practices were broadly similar in terms of drug usage and assessment tools. Sedation protocols linking assessment to appropriate titration of sedatives and sedation holds were rarely used (9 % and 4 % of PICUs respectively). Ventilator weaning was primarily a medical-led process with 39 % of PICUs engaging senior nurses in the process: weaning protocols were rarely used (9 % of PICUs). Weaning methods were variably based on clinician preference. No formal criteria or use of spontaneous breathing trials were used to test weaning readiness. Seventeen PICUs (74 %) had prior engagement in multi-centre trials, but limited research nurse availability. Barriers to previous trial implementation were intervention complexity, lack of belief in the evidence and inadequate training. Facilitating factors were senior staff buy-in and dedicated research nurse provision. Conclusions: We examined and identified contextual and organisational factors that may impact on the implementation of our intervention. We found usual practice relating to sedation, analgesia and ventilator weaning broadly similar, yet distinctively different from our proposed intervention, providing assurance in our ability to evaluate intervention effects. The data will enable us to develop an implementation plan; considering these factors we can more fully understand their impact on study outcomes

QuantiFERON®-TB gold in-tube performance for diagnosing active tuberculosis in children and adults in a high burden setting.

To determine whether QuantiFERON®-TB Gold In-Tube (QFT) can contribute to the diagnosis of active tuberculosis (TB) in children in a high-burden setting and to assess the performance of QFT and tuberculin skin test (TST) in a prospective cohort of TB suspect children compared to adults with confirmed TB in Tanzania. Sensitivity and specificity of QFT and TST for diagnosing active TB as well as indeterminate QFT rates and IFN-γ levels were assessed in 211 TB suspect children in a Tanzanian district hospital and contrasted in 90 adults with confirmed pulmonary TB. Sensitivity of QFT and TST in children with confirmed TB was 19% (5/27) and 6% (2/31) respectively. In adults sensitivity of QFT and TST was 84% (73/87) and 85% (63/74). The QFT indeterminate rate in children and adults was 27% and 3%. Median levels of IFN-γ were lower in children than adults, particularly children <2 years and HIV infected. An indeterminate result was associated with age <2 years but not malnutrition or HIV status. Overall childhood mortality was 19% and associated with an indeterminate QFT result at baseline. QFT and TST showed poor performance and a surprisingly low sensitivity in children. In contrast the performance in Tanzanian adults was good and comparable to performance in high-income countries. Indeterminate results in children were associated with young age and increased mortality. Neither test can be recommended for diagnosing active TB in children with immature or impaired immunity in a high-burden setting

Rotation and Spin in Physics

We delineate the role of rotation and spin in physics, discussing in order Newtonian classical physics, special relativity, quantum mechanics, quantum electrodynamics and general relativity. In the latter case, we discuss the generalization of the Kepler formula to post-Newtonian order $(c^{-2}$) including spin effects and two-body effects. Experiments which verify the theoretical results for general relativistic spin-orbit effects are discussed as well as efforts being made to verify the spin-spin effects

Recommendations for a core outcome set for measuring standing balance in adult populations: a consensus-based approach

Standing balance is imperative for mobility and avoiding falls. Use of an excessive number of standing balance measures has limited the synthesis of balance intervention data and hampered consistent clinical practice.To develop recommendations for a core outcome set (COS) of standing balance measures for research and practice among adults.A combination of scoping reviews, literature appraisal, anonymous voting and face-to-face meetings with fourteen invited experts from a range of disciplines with international recognition in balance measurement and falls prevention. Consensus was sought over three rounds using pre-established criteria.The scoping review identified 56 existing standing balance measures validated in adult populations with evidence of use in the past five years, and these were considered for inclusion in the COS.Fifteen measures were excluded after the first round of scoring and a further 36 after round two. Five measures were considered in round three. Two measures reached consensus for recommendation, and the expert panel recommended that at a minimum, either the Berg Balance Scale or Mini Balance Evaluation Systems Test be used when measuring standing balance in adult populations.Inclusion of two measures in the COS may increase the feasibility of potential uptake, but poses challenges for data synthesis. Adoption of the standing balance COS does not constitute a comprehensive balance assessment for any population, and users should include additional validated measures as appropriate.The absence of a gold standard for measuring standing balance has contributed to the proliferation of outcome measures. These recommendations represent an important first step towards greater standardization in the assessment and measurement of this critical skill and will inform clinical research and practice internationally