One lithium level >1.0 mmol/L causes an acute decline in eGFR: findings from a retrospective analysis of a monitoring database

Objectives Lithium is a mainstay of bipolar disorder treatment, however, there are still differences in opinion on the effects of lithium use on renal function. The aim of this analysis was to determine if there is an association between short-term exposure to various elevated lithium levels and estimated-glomerular filtration rate (eGFR) at ≤3 months, 6 months (±3 months) and 1 year (±3 months) follow-up. Setting Norfolk-wide (UK) lithium register and database. Participants 699 patients from the Norfolk database. Primary outcome measures eGFR change from baseline at ≤3 months, 6 months (±3 months) and 1 year (±3 months) after exposure to a lithium level within these ranges: 0.81–1.0 mmol/L (group 2), 1.01–1.2 mmol/L (group 3) and 1.21–2.0 mmol/L (group 4). The reference group was patients whose lithium levels never exceeded 0.8 mmol/L. Results Compared to the reference group, groups 3 and 4 showed a significant decrease in eGFR in the first 3 months after exposure (p=0.047 and p=0.040). At 6 months (±3 months) postexposure group 4 still showed a decline in eGFR, however, this result was not significant (p=0.298). Conclusions These results show for the first time that a single incident of a lithium level >1.0 mmol/L is associated with a significant decrease in eGFR in the following 3 months when compared to patients whose lithium levels never exceeded 0.8 mmol/L. It is still not known whether the kidneys can recover this lost function and the impact that more than a single exposure to a level within these ranges can have on renal function. These results suggest that lithium level monitoring should be undertaken at least every 3 months, in line with current UK guidelines and not be reduced further until the impact of more than one exposure to these lithium levels has been fully established

From initial prescribing to long-term management: what is the role of lithium monitoring?

Lithium is currently licensed for the treatment and prophylaxis of recurrent affective disorders, treatment of bipolar depression where the use of antidepressants has been ineffective, and the treatment of aggressive or self-mutilating behaviour. Lithium requires therapeutic drug monitoring (TDM) during treatment and evidence is lacking to support the recommended monitoring frequencies of lithium levels. A retrospective analysis of a monitoring database was run to establish the association of single and double exposures of various lithium levels on renal function. Interviews were also conducted with prescribers to establish the factors affecting prescribing decisions related to lithium. This study suggests there is a short-term negative association on renal function after exposures to single, high lithium levels but due to the small patient groups in the multiple exposures analysis the results from this are not statistically reliable. These results did, however, raise the considerations that changes in lithium levels may impact on renal function. This work added to the factors influencing prescribing decisions surrounding knowledge, learning and competence of prescribers with concerns around a lack of knowledge of older drugs seen in newer doctors. Guidance surrounding at what points during the patient’s journey the initial prescribing choice and a decision should be made is also needed. This would help overcome the barrier of split services within mental health and give clearer roles to the various consultants involved in a patient’s care and aid in the involvement of the patient with their treatment. iii The roll out of a centralised lithium monitoring system with access for all those involved in the patients care could be considered to aid in the long-term monitoring of lithium. . This sort of system would also allow for all those involved being able to retain oversight over patients whether or not they are still directly under their care

Outcome reporting bias in Cochrane systematic reviews: a cross-sectional analysis

Background Discrepancies in outcome reporting (DOR) between protocol and published studies include inclusions of new outcomes, omission of prespecified outcomes, upgrade and downgrade of secondary and primary outcomes, and changes in definitions of prespecified outcomes. DOR can result in outcome reporting bias (ORB) when changes in outcomes occur after knowledge of results. This has potential to overestimate treatment effects and underestimate harms. This can also occur at the level of systematic reviews when changes in outcomes occur after knowledge of results of included studies. The prevalence of DOR and ORB in systematic reviews is unknown in systematic reviews published post-2007. Objective To estimate the prevalence of DOR and risk of ORB in all Cochrane reviews between the years 2007 and 2014. Methods A stratified random sampling approach was applied to collect a representative sample of Cochrane systematic reviews from each Cochrane review group. DOR was assessed by matching outcomes in each systematic review with their respective protocol. When DOR occurred, reviews were further assessed if there was a risk of ORB (unclear, low or high risk). We classified DOR as a high risk for ORB if the discrepancy occurred after knowledge of results in the systematic review. Results 150 of 350 (43%) review and protocol pairings contained DOR. When reviews were further scrutinised, 23% (35 of 150) of reviews with DOR contained a high risk of ORB, with changes being made after knowledge of results from individual trials. Conclusions In our study, we identified just under a half of Cochrane reviews with at least one DOR. Of these, a fifth were at high risk of ORB. The presence of DOR and ORB in Cochrane reviews is of great concern; however, a solution is relatively simple. Authors are encouraged to be transparent where outcomes change and to describe the legitimacy of changing outcomes in order to prevent suspicion of bias

Using a Socio-Technical Approach to Explore Perceptions of the Graffiti Culture

The effectiveness of socio-technical approaches, such as the Soft Systems Methodology (SSM), to structure problematic situations is dependent on the candid communication of participants. This paper reports a pilot study using SSM to explore the challenges of establishing the Ideal Speech Situation in order to gain an understanding of the contradictory perceptions of graffiti. Through exploring this social phenomenon from the views of both graffiti writers and the general public, power and ego were identified as challenges to establishing an Ideal Speech Situation. Analysing these challenges in the context of graffiti provides insight into how these barriers may hinder the effective application of socio-technical approaches

Mothering, Albinism and Human Rights: The Disproportionate Impact of Health-Related Stigma in Tanzania

In many parts of sub-Saharan Africa, mothers impacted by the genetic condition of albinism, whether as mothers of children with albinism or themselves with albinism, are disproportionately impacted by a constellation of health-related stigma, social determinants of health (SDH), and human rights violations. In a critical ethnographic study in Tanzania, we engaged with the voices of mothers impacted by albinism and key stakeholders to elucidate experiences of stigma. Their narratives revealed internalized subjective stigma, social stigma such as being ostracized by family and community, and structural stigma on account of lack of access to SDH. An analysis of health systems as SDH revealed stigmatizing attitudes and behaviours of healthcare providers, especially at the time of birth; a lack of access to timely quality health services, in particular skin and eye care; and a lack of health-related education about the cause and care of albinism. Gender inequality as another SDH featured prominently as an amplifier of stigma. The findings pose implications for research, policy, and practice. A concrete avenue to de-stigmatization of mothers impacted by albinism exists by the application of principles of human rights, particularly equality and non-discrimination; contextual analysis of cultural dynamics including relevant ontology; meaningful participation of rights-claimants, such as peer groups of mothers; and accountability of governments and their obligation to ensure access to health information as a key social determinant of the right to health

Constructing social meaning in political discourse: Phonetic variation and verb processes in Ed Miliband's speeches

This article investigates how variation across different levels of linguistic structure indexes ideological alignments in political talk. We analyse two political speeches by Ed Miliband, the former leader of the UK Labour Party, with a focus on the use of /t/-glottalling and the types of verb processes that co-occur with the pronouns we and you. We find substantial differences in the production of /t/ between the two speeches in words such as Britain and government, which have been argued to take on particular salience in British political discourse. We contextualise these findings in terms of metalinguistic discourse surrounding Miliband's language use, as well as how he positions himself in relation to different audiences via verb process types. We show that phonetic variation, subject types, and verb processes work synergistically in allowing Miliband to establish a political persona that is sensitive to ideological differences between different audiences. (Social meaning, indexicality, political discourse, verb processes, phonetic variation, /t/-glottalling)*

The effect of Korean pine nut oil (PinnoThin™) on food intake, feeding behaviour and appetite: A double-blind placebo-controlled trial

Certain free fatty acids have been shown to have potent effects on food intake and self-reported changes in appetite; effects associated with increases in the release of endogenous cholecystokinin (CCK) and glucagon like peptide-1 (GLP-1). In the current study, the effects of a Korean pine nut oil product, PinnoThin™, at doses 2 g, 4 g and 6 g triglyceride (TG) and 2 g free fatty acid (FFA), on food intake and appetite were examined in a cross-over double-blind placebo-controlled randomised counter-balanced design in 42 overweight female volunteers. 2 g FFA PinnoThin™, given 30 minutes prior to an ad-libitum buffet test lunch, significantly reduced food intake (gram) by 9% (F(4,164) = 2.637, p = 0.036) compared to olive oil control. No significant effect of PinnoThin™ on macronutrient intake or ratings of appetite were observed. Given the recent data showing that the TG form of PinnoThin™ may also reduce appetite by increasing CCK release, the lack of any effect of the TG form found in this study could be attributed to the timing of the dosing regime. Collectively, these data suggest that PinnoThin™ may exert satiating effects consistent with its known action on CCK and GLP-1 release, and previously observed effects on self-reported appetite ratings

Splinting for the non-operative management of developmental dysplasia of the hip (DDH) in children under six months of age

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the role of splinting and the optimal treatment strategy for the non-operative management of DDH in children under six months of age. To identify if there are particular subgroups of patients for whom the optimal management strategy may differ

Drift-dependent changes in iceberg size-frequency distributions

Although the size-frequency distributions of icebergs can provide insight into how they disintegrate, our understanding of this process is incomplete. Fundamentally, there is a discrepancy between iceberg power-law size-frequency distributions observed at glacial calving fronts and lognormal size-frequency distributions observed globally within open waters that remains unexplained. Here we use passive seismic monitoring to examine mechanisms of iceberg disintegration as a function of drift. Our results indicate that the shift in the size-frequency distribution of iceberg sizes observed is a product of fracture-driven iceberg disintegration and dimensional reductions through melting. We suggest that changes in the characteristic size-frequency scaling of icebergs can be explained by the emergence of a dominant set of driving processes of iceberg degradation towards the open ocean. Consequently, the size-frequency distribution required to model iceberg distributions accurately must vary according to distance from the calving front

Mapping a research-advocacy-policy agenda on human rights and albinism: a mixed methods project

Background: Persons with albinism face challenges to their wellbeing, safety, and security, ranging from vision impairment and skin cancer to stigma and discrimination. In some regions, they also face human rights atrocities including mutilation and murder. Research on human rights and albinism is a relatively new field that has gained momentum since the United Nations appointment of an Independent Expert on the enjoyment of human rights by persons with albinism. In this paper, we present the results of a mixed methods study undertaken to identify priorities for research, advocacy, and policy on albinism and human rights. Methods: The first component was a synthesis of peer-reviewed and grey literatures at the nexus of albinism, spiritual/cultural beliefs and practices, and human rights. We then conducted a priority-setting survey, informed by Delphi methods, on extant knowledge-practice gaps and research, advocacy, and policy priorities. Inclusion criteria included demonstrated expertise in the field (e.g., peer-reviewed publications, funded research), membership on national or international associations, or advocacy (civil society organizations) of more than 2 years in albinism and human rights. Thereafter, we gathered leading researchers, policy-makers, and civil society stakeholders for a Roundtable to gain consensus on these priorities. Results: Access to skin and vision care, and education were not deemed high priority for research, likely because the evidence supporting the need for these is well established. However, they were priorities for advocacy and policy: what is needed is mobilization of this evidence through advocacy and implementation of such services (policy). Other social determinants of health (rurality, poverty, and gender equality) are present as subtext in the findings, more so than priorities for research, advocacy, or policy, despite their preponderance in the lives of persons with albinism. Research was prioritized on stigma and discrimination; advocacy; and witchcraft, but with some differentiation between Global North and Global South priorities. Priorities for research, advocacy, and policy vary in keeping with the explanatory frameworks at play, including how harmful practices and witchcraft are viewed. Conclusions: The lived experience of albinism is profoundly shaped by the social determinants of health (SDOH). Threats to the security and well-being of persons with albinism should be viewed through a human rights lens that encompasses the explanatory frameworks at play