The benefits of transcutaneous electrical nerve stimulation (TENS) for pain relief have not been reliably established, as most systematic reviews find poor methodological quality in many studies. The paradox within the evidence base for TENS is that despite identified sources of bias that may lead to an overestimation of treatment effects, no benefits for TENS can be clearly demonstrated. Conventional assessments of quality assume a single direction of bias, and little work has been undertaken examining other directions of bias. Our hypothesis was that low fidelity in studies (bias leading to an underestimation of treatment effects) may account for inconclusive findings. We included 38 studies from 3 recently published Cochrane systematic reviews that examined TENS for acute, chronic, and cancer pain. We extracted data relating to treatment allocation, application of TENS and to the assessment of outcomes. We quantified these data and judged this against standardised assessment criteria using a "traffic light" approach based on the number of studies reaching the standard. We identified significant sources of potential bias in both directions in relation to study design and implementation fidelity that have not been quantified previously. Suboptimal dosing of TENS and inappropriate outcome assessment were particularly prevalent weaknesses indicating low fidelity. We propose criteria for judging directions of bias in future studies of TENS that may be adapted to assess other trials in which implementation fidelity is important, such as other nonpharmacological interventions for pain. Poor implementation fidelity was identified as a significant source of bias in systematic reviews of TENS studies and might explain lack of consistent treatment effects of TENS in pain. Here, criteria for assessing methodology are proposed for use in designing future clinical trials of TENS.

This paper reports on a research study of five patients diagnosed with mesothelioma. The study used a phenomenological approach to explore patients' lived experience using in-depth interviews. The findings identify that patients have many unmet psychosocial and emotional needs and that there was a lack of information provided to patients about specialist supportive and palliative care services. A number of the patients found specialist supportive care by chance rather than by referral. In addition, patients were involved in complex medico-legal matters in relation to asbestos exposure, and this was an additional burden for them and their spouse or carer. A feeling of social isolation was also reported and a number of patients would welcome the opportunity to meet with other people in the same situation as themselves. In conclusion, there is a lack of attention to the emotional needs of this group of patients, which means that supportive care resources are not being accessed in a timely and flexible manner.

Summary Adherence to anti-osteoporosis medications is currently low and is associated with poor anti-fracture efficacy. This manuscript reviews the potential design of clinical studies that aim to demonstrate improved adherence, with new chemical entities to be used in the management of osteoporosis.

Adolescents and Young Adults (AYA) with cancer are young people developing serious illness when at the interface between the responsibilities of paediatric and adult cancer services. Personally, they are in a period of transition both biologically and in major social roles (Sawyer et al., 2018) [1]. For these and other reasons they present a unique set of clinical challenges in their management. Over the last 20 years the requirement for specific services to address their needs has been identified and this has become a growing field of research. Despite this survival rates still lag behind those of children and older adults with cancer (Gatta et al., 2009) [2]. Why do AYA patients have worse outcomes? The observation is that the reason is multifactorial with path to diagnosis, unique cancer biology, uncertainty of treatment protocol, compliance issues and poor recruitment to clinical trials all playing a part. In this review we will discuss the unique challenges faced by healthcare professionals when managing AYA patients who are commonly and accurately described as being in an 'interface' position.

Background and Purpose Hypoxia in tumours is known to cause resistance to conventional chemotherapeutic drugs. In contrast, little is known about the effects of hypoxia on targeted anti‐cancer drugs. This study evaluated the effect of hypoxia on a series of clinically approved tyrosine kinase inhibitors (TKIs). Experimental Approach The effect of hypoxia (0.1% oxygen) on the activity of conventional cytotoxic drugs (5‐fluorouracil, doxorubicin and vinblastine), the hypoxia‐activated prodrug tirapazamine and 9 TKIs was determined in a panel of cell lines. Where hypoxia had a marked effect on chemosensitivity, Western blot analysis was conducted to determine the effect of hypoxia on target expression and the effect of TKIs on cell signalling response under aerobic and hypoxic conditions. Key Results Three patterns of chemosensitivity were observed: resistance under hypoxia, equitoxic activity against hypoxic and aerobic cells, and preferential cytotoxicity to hypoxic cells. Significant hypoxia selectivity (independent of HIF1) was observed in the case of dasatinib and this correlated with the ability of dasatinib to inhibit phosphorylation of Src at tyrosine 530. Sorafenib was significantly less effective under hypoxic conditions but resistance did not correlate with hypoxia‐induced changes in Raf/MEK/ERK signalling. Conclusions and Implications Hypoxia influences the activity of TKIs but in contrast to conventional cytotoxic drugs, preferential activity against hypoxic cells can occur. The search for hypoxia‐targeted therapies has been long and fruitless and this study suggests that some clinically approved TKIs could preferentially target the hypoxic fraction of some tumour types.

TENS is most comfortable and easiest to titrate to a strong nonpainful intensity when applied over areas of muscle and soft tissue.

As prison populations increase, the need for successful reintegration of ex-prisoners becomes more pressing. The challenge of what has become known as `re-entry' has stimulated an extensive body of research, much of it concentrated in a small number of jurisdictions and concerned with levels and predictors of recidivism. The limited geographic breadth of the research effort has hindered our capacity to consider theoretically relevant questions, such as whether particular societal conditions thought to be conducive to successful prisoner reintegration (e.g. high levels of social capital and informal social control) in fact translate into lower levels of recidivism. In this article we expand the reach of existing research by exploring levels and patterns of recidivism in uncharted territory—the Republic of Ireland—and by drawing out the implications of the patterns observed there for comparative analysis.

The Group support interactions between the industry and clinicians provided that it is transparent and ethical.