Subcutaneous sodium valproate in palliative care: A systematic review.

BACKGROUND: Seizures are an important palliative symptom, the management of which can be complicated by patients' capacity to swallow oral medications. In this setting, and the wish to avoid intravenous access, subcutaneous infusions may be employed. Options for antiseizure medications that can be provided subcutaneously may be limited. Subcutaneous sodium valproate may be an additional management strategy. AIM: To evaluate the published experience of subcutaneous valproate use in palliative care, namely with respect to effectiveness and tolerability. DESIGN: A systematic review was registered (PROSPERO CRD42023453427), conducted and reported according to PRISMA reporting guidelines. DATA SOURCES: The databases PubMed, EMBASE and Scopus were searched for publications until August 11, 2023. RESULTS: The searches returned 429 results, of which six fulfilled inclusion criteria. Case series were the most common study design, and most studies included <10 individuals who received subcutaneous sodium valproate. There were three studies that presented results on the utility of subcutaneous sodium valproate for seizure control, which described it to be an effective strategy. One study also described it as an effective treatment for neuropathic pain. The doses were often based on presumed 1:1 oral to subcutaneous conversion ratios. Only one study described a local site adverse reaction, which resolved with a change of administration site. CONCLUSIONS: There are limited data on the use of subcutaneous sodium valproate in palliative care. However, palliative symptoms for which subcutaneous sodium valproate have been used successfully are seizures and neuropathic pain. The available data have described few adverse effects, supporting its use with an appropriate degree of caution.

Identifying epilepsy surgery referral candidates with natural language processing in an Australian context.

OBJECTIVE: Epilepsy surgery is known to be underutilized. Machine learning-natural language processing (ML-NLP) may be able to assist with identifying patients suitable for referral for epilepsy surgery evaluation. METHODS: Data were collected from two tertiary hospitals for patients seen in neurology outpatients for whom the diagnosis of "epilepsy" was mentioned. Individual case note review was undertaken to characterize the nature of the diagnoses discussed in these notes, and whether those with epilepsy fulfilled prespecified criteria for epilepsy surgery workup (namely focal drug refractory epilepsy without contraindications). ML-NLP algorithms were then developed using fivefold cross-validation on the first free-text clinic note for each patient to identify these criteria. RESULTS: There were 457 notes included in the study, of which 250 patients had epilepsy. There were 37 (14.8%) individuals who fulfilled the prespecified criteria for epilepsy surgery referral without described contraindications, 32 (12.8%) of whom were not referred for epilepsy surgical evaluation in the given clinic visit. In the prediction of suitability for epilepsy surgery workup using the prespecified criteria, the tested models performed similarly. For example, the random forest model returned an area under the receiver operator characteristic curve of 0.97 (95% confidence interval 0.93-1.0) for this task, sensitivity of 1.0, and specificity of 0.93. SIGNIFICANCE: This study has shown that there are patients in tertiary hospitals in South Australia who fulfill prespecified criteria for epilepsy surgery evaluation who may not have been referred for such evaluation. ML-NLP may assist with the identification of patients suitable for such referral. PLAIN LANGUAGE SUMMARY: Epilepsy surgery is a beneficial treatment for selected individuals with drug-resistant epilepsy. However, it is vastly underutilized. One reason for this underutilization is a lack of prompt referral of possible epilepsy surgery candidates to comprehensive epilepsy centers. Natural language processing, coupled with machine learning, may be able to identify possible epilepsy surgery candidates through the analysis of unstructured clinic notes. This study, conducted in two tertiary hospitals in South Australia, demonstrated that there are individuals who fulfill criteria for epilepsy surgery evaluation referral but have not yet been referred. Machine learning-natural language processing demonstrates promising results in assisting with the identification of such suitable candidates in Australia.

The Portrayal of Premium Cigar Selling Propositions in Lifestyle Magazines: A Content Analysis.

INTRODUCTION: Although lifestyle magazines are an important marketing tool for premium cigars, little is known about their recent portrayal of the products. We expand on research conducted for the National Academies of Sciences, Engineering, and Medicine's Committee on Patterns of Use and Health Effects of "Premium Cigars" and Priority Research. AIMS AND METHODS: A content analysis of magazine covers, articles, and advertisements published in 2021 from Cigar Aficionado and Cigar Snob (five issues each) and Cigar Journal (three issues) assessed magazine themes and mentions of lower harm. Magazine covers (n = 14), advertisements (n = 105), and every fifth article (n = 45) were coded. RESULTS: In total, 92% of the magazine covers, 72.4% of advertisements, and 62.2% of articles had premium cigar content. Celebrities (e.g. musicians and actors) appeared on 92.9% of covers. The most common themes in the advertisements and articles were "high quality." Regarding article content, 80% portrayed the premium cigars' quality (e.g. superior materials), and the taste of featured products (e.g. "tones," "aromas," and "notes") was portrayed in 42.4%. While no articles described their health risks, 6.7% described the positive health effects of premium cigar use (e.g. stress relief and clear cognition). Additionally, a digital search of Cigar Snob and Cigar Aficionado for terms related to lower harm (e.g. "organic," "healthy," "clean," "pure," and "natural") found 7.7 mentions of lower-harm words per issue. CONCLUSIONS: Our findings indicate that lifestyle magazines are an important marketing strategy that promotes and normalizes premium cigar use as a high-quality product that can have positive health effects for users. IMPLICATIONS: Our manuscript characterized the premium cigar companies' use of selling propositions, including promoting the products' features, safety, taste, and flavors, as a part of their advertising promotion practices. Premium cigar companies used digital and print lifestyle magazines as marketing tools to promote and normalize the use of their products by emphasizing their high quality and positive health benefits (e.g. reducing stress). Premium cigars were promoted as a symbol of power and success, featured in advertisements of upscale social events (e.g. exclusive trade shows, social clubs, and lounges), and often juxtaposed with expensive alcohol, food, and other luxurious goods. Future research should assess if exposure to premium cigar content increases consumer appeal and detracts from the products' potential adverse health outcomes.

The Promotion of Premium Cigars on Social Media.

INTRODUCTION: The health effect of premium cigar smoking is determined by patterns of use and perceptions, which are shaped by marketing messages. The tobacco industry uses brand-owned media promotion on social media to market its product. However, premium cigar brands' promotion of their products on social media is unknown. AIMS AND METHODS: Forty-seven premium cigar brands were reviewed. For each brand, we identified the social media accounts and examined the content of the 10 most recent posts of each social media platform to identify the marketing themes in July 2022. We also assessed the presence of age-gating and the dates of the posts. RESULTS: Of the 47 brands, 65% (n = 31) had Facebook and Instagram, 56% (n = 27) had Twitter, 21% (n = 10) had YouTube, and 17% (n = 8) had "other" (e.g. LinkedIn and Pinterest) accounts. Age-gating across these platforms ranged from 0% to 49%. Marketing themes identified from 981 social media posts included product features, alcohol, holidays, events and festivals, discounts and sweepstakes, taste, family, quality, lounges and clubs, culture, innovation, masculinity, and "other" (e.g. fundraising for charity and celebrity endorsement). CONCLUSIONS: Premium cigar brands are using brand-owned social media to promote their products using similar strategies (e.g. discounts and sweepstakes) used by other tobacco industries but also using novel themes (e.g. fundraising for charity, events and festivals) to enhance engagement. Ongoing comprehensive surveillance of premium cigars' marketing is needed on social media to inform marketing restrictions to protect public health, including priority populations such as youth. IMPLICATIONS: This study is the first to identify that premium cigar brands are promoting their brands and products on brand-owned social media, using diverse themes and strategies to engage and appeal to the public. Age gating of the promotional content on social media was low. Findings suggest that marketing restrictions to reduce the appeal of premium cigars among youth is needed to reduce tobacco-related harm.

Delays in the diagnosis of ischaemic stroke presenting with persistent reduced level of consciousness: A systematic review.

INTRODUCTION: Stroke presenting with a reduced level of consciousness (RLOC) may result in diagnostic error and/or delay. Missed or delayed diagnosis of acute ischaemic stroke may preclude otherwise applicable hyperacute stroke interventions. The frequency, reasons for, and consequences of diagnostic error and delay due to RLOC are uncertain. METHOD: The databases PubMed, EMBASE, and Cochrane library were searched in adherence with the PRISMA guidelines. The systematic review was prospectively registered on PROSPERO. RESULTS: Initial searches returned 1162 results, of which 6 fulfilled inclusion criteria. The majority of identified studies show that ischaemic stroke presenting with RLOC is at increased risk of missed or delayed diagnosis. Hyperacute stroke interventions may also be delayed. There is limited evidence regarding the reason for these delays; however, the delays may result from neuroimaging delay associated with diagnostic uncertainty. There is also limited evidence regarding the outcomes of patients with stroke and RLOC who experience diagnostic delay; however, the available literature suggests that outcomes may be poor, including motor and cognitive impairment, as well as long-term impaired consciousness. The included studies did not evaluate, but have suggested urgent MRI access, educational interventions, and protocolisation of the evaluation of RLOC as means to reduce poor outcomes. CONCLUSIONS: Ischaemic stroke patients with RLOC are at risk of diagnostic delay and error. These patients may have poor outcomes. Additional research is required to identify the contributing factors more clearly and to provide amelioration strategies.

Genomics Research with Undiagnosed Children: Ethical Challenges at the Boundaries of Research and Clinical Care.

OBJECTIVE: To explore the perspectives of parents of undiagnosed children enrolled in genomic diagnosis research regarding their motivations for enrolling their children, their understanding of the potential burdens and benefits, and the extent to which their experiences ultimately aligned with or diverged from their original expectations. STUDY DESIGN: In-depth interviews were conducted with parents, audio-recorded and transcribed. A structured codebook was applied to each transcript, after which iterative memoing was used to identify themes. RESULTS: Fifty-four parents participated, including 17 (31.5%) whose child received a diagnosis through research. Themes describing parents' expectations and experiences of genomic diagnosis research included (1) the extent to which parents' motivations for participation focused on their hope that it would directly benefit their child, (2) the ways in which parents' frustrations regarding the research process confused the dual clinical and research goals of their participation, and (3) the limited clinical benefits parents ultimately experienced for their children. CONCLUSIONS: Our results suggest that parents of undiagnosed children seeking enrollment in genomic diagnosis research are at risk of a form of therapeutic misconception-in this case, diagnostic misconception. These findings indicate the need to examine the processes and procedures associated with this research to communicate appropriately and balance the potential burdens and benefits of study participation.

Identifying epilepsy surgery candidates with natural language processing: A systematic review.

INTRODUCTION: Epilepsy surgery is an underutilised, efficacious management strategy for selected individuals with drug-resistant epilepsy. Natural language processing (NLP) may aid in the identification of patients who are suitable to undergo evaluation for epilepsy surgery. The feasibility of this approach is yet to be determined. METHOD: In accordance with the PRISMA guidelines, a systematic review of the databases PubMed, EMBASE and Cochrane library was performed. This systematic review was prospectively registered on PROSPERO. RESULTS: 6 studies fulfilled inclusion criteria. The majority of included studies reported on datasets from only a single centre, with one study utilising data from two centres and one study six centres. The most commonly employed algorithms were support vector machines (5/6), with only one study utilising NLP strategies such as random forest models and gradient boosted machines. However, the results are promising, with all studies demonstrating moderate to high levels of performance in the identification of patients who may be suitable to undergo epilepsy surgery evaluation. Furthermore, multiple studies demonstrated that NLP could identify such patients 1-2 years prior to the treating clinicians instigating referral. However, no studies were identified that have evaluated the influence of implementing such algorithms on healthcare systems or patient outcomes. CONCLUSIONS: NLP is a promising approach to aid in the identification of patients that may be suitable to undergo epilepsy surgery evaluation. Further studies are required examining diverse datasets with additional analytical methodologies. Studies evaluating the impact of implementation of such algorithms would be beneficial.

Estimated Clinical Trial Capacity of Sites Participating in the COVID-19 Convalescent Plasma Expanded Access Program.

This cross-sectional study estimates the trial capacity of sites participating in the COVID-19 convalescent plasma expanded access program.

Synaptic inputs to broad thorny ganglion cells in macaque retina.

In primates, broad thorny retinal ganglion cells are highly sensitive to small, moving stimuli. They have tortuous, fine dendrites with many short, spine-like branches that occupy three contiguous strata in the middle of the inner plexiform layer. The neural circuits that generate their responses to moving stimuli are not well-understood, and that was the goal of this study. A connectome from central macaque retina was generated by serial block-face scanning electron microscopy, a broad thorny cell was reconstructed, and its synaptic inputs were analyzed. It received fewer than 2% of its inputs from both ON and OFF types of bipolar cells; the vast majority of its inputs were from amacrine cells. The presynaptic amacrine cells were reconstructed, and seven types were identified based on their characteristic morphology. Two types of narrow-field cells, knotty bistratified Type 1 and wavy multistratified Type 2, were identified. Two types of medium-field amacrine cells, ON starburst and spiny, were also presynaptic to the broad thorny cell. Three types of wide-field amacrine cells, wiry Type 2, stellate wavy, and semilunar Type 2, also made synapses onto the broad thorny cell. Physiological experiments using a macaque retinal preparation in vitro confirmed that broad thorny cells received robust excitatory input from both the ON and the OFF pathways. Given the paucity of bipolar cell inputs, it is likely that amacrine cells provided much of the excitatory input, in addition to inhibitory input.