Preliminary evaluation of a smartphone application (DelApp) for identification of delirium in sub-Saharan Africa.

OBJECTIVE: In sub-Saharan Africa, there are no validated screening tools for delirium in older adults, despite the known vulnerability of older people to delirium and the associated adverse outcomes. This study aimed to assess the effectiveness of a brief smartphone-based assessment of arousal and attention (DelApp) in the identification of delirium amongst older adults admitted to the medical department of a tertiary referral hospital in Northern Tanzania. METHOD: Consecutive admissions were screened using the DelApp during a larger study of delirium prevalence and risk factors. All participants subsequently underwent detailed clinical assessment for delirium by a research doctor. Delirium and dementia were identified against DSM-5 criteria by consensus. RESULTS: Complete data for 66 individuals were collected of whom 15 (22.7%) had delirium, 24.5% had dementia without delirium, and 10.6% had delirium superimposed on dementia. Sensitivity and specificity of the DelApp for delirium were 0.87 and 0.62, respectively (AUROC 0.77) and 0.88 and 0.73 (AUROC 0.85) for major cognitive impairment (dementia and delirium combined). Lower DelApp score was associated with age, significant visual impairment (<6/60 acuity), illness severity, reduced arousal and DSM-5 delirium on univariable analysis, but on multivariable logistic regression only arousal remained significant. CONCLUSION: In this setting, the DelApp performed well in identifying delirium and major cognitive impairment but did not differentiate delirium and dementia. Performance is likely to have been affected by confounders including uncorrected visual impairment and reduced level of arousal without delirium. Negative predictive value was nevertheless high, indicating excellent 'rule out' value in this setting.

Influences on indoor environmental trigger remediation uptake for children and young people with asthma: A scoping review.

INTRODUCTION: Children and young people (CYP) with asthma can benefit from reduced exposure to indoor environmental allergens and triggers but may not consistently have avoidance strategies implemented. To inform future interventions to increase trigger and allergen avoidance and enhance asthma control, a greater understanding of the influences on avoidance behaviours is necessary. METHODS: A systematic scoping review was selected to summarize evidence on what influences family uptake of indoor environmental asthma trigger avoidance strategies for CYP with asthma and identify research gaps. Primary studies of any design, including CYP (≤18 years) with asthma, and/or parent-carers, available in English and conducted since 1993, were eligible. Searches included nine databases, hand-searching reference lists and citation searching. FINDINGS: Thirty-three articles were included and are summarized narratively due to heterogeneity. Influences appear complex and multifactorial and include barriers to strategy uptake, health beliefs and personal motivation. Research specifically related to family understanding of allergic sensitisation status and exposure risks, and how these may inform avoidance implementation is required. Patient and public involvement (PPI) was not reported in included articles, although two studies used participatory methods. CONCLUSION: There is limited research on family asthma trigger management, particularly what influences current management behaviours. Variation in families' ability to identify important triggers, understand exposure risk and consistently reduce exposures warrants further exploratory research to explain how families reach avoidance decisions, and what future interventions should aim to address. Further PPI-informed research to address such gaps, could enable theory-based, person-centred interventions to improve the uptake of asthma trigger remediation. PATIENT OR PUBLIC CONTRIBUTION: An asthma-specific PPI group contributed to the decision-making for the funding for the wider project this review sits within. The findings of this scoping review have informed the subsequent phases of the project, and this was discussed with PPI groups (both adult and CYP groups) when proposing the next phases of the project.

Risk of serious COVID-19 outcomes among adults and children with moderate-to-severe asthma: a systematic review and meta-analysis.

BACKGROUND: The Joint Committee on Vaccination and Immunisation in the United Kingdom requested an evidence synthesis to investigate the relationship between asthma and coronavirus disease 2019 (COVID-19) outcomes. OBJECTIVE: We conducted a systematic review and meta-analysis to summarise evidence on the risk of severe COVID-19 outcomes in people with uncontrolled asthma or markers of asthma severity. METHODS: High-dose inhaled corticosteroids (ICS) or oral corticosteroids (OCS) were used as markers of asthma severity, following international or national asthma guidelines. Risk of bias was assessed using Joanna Briggs Institute tools. Adjusted point estimates were extracted for random-effects meta-analyses and subgroup analyses. RESULTS: After screening, 12 studies (11 in adults and one in children) met the eligibility criteria. Adults using high-dose ICS or OCS had a pooled adjusted hazard ratio (aHR) of 1.33 (95% CI 1.06-1.67, I2=0%) for hospitalisation and an aHR of 1.22 (95% CI 0.90-1.65, I2=70%) for mortality for COVID-19. We found insufficient evidence for associations between markers on COVID-19 mortality in the subgroup analyses. CONCLUSIONS: Adults with severe asthma are at increased risk of COVID-19 hospitalisation compared to nonusers. Our analysis highlighted the dearth of studies in children with asthma investigating serious COVID-19 outcomes.

Chemical explosion, COVID-19, and environmental justice: Insights from low-cost air quality sensors.

OBJECTIVES: To examine the impact of the Intercontinental Terminals Company (ITC) fire and COVID-19 on airborne particulate matter (PM) concentrations and the PM disproportionally affecting communities in Houston using low-cost sensors. METHODS: We compared measurements from a network of low-cost sensors with a separate network of monitors from the Environmental Protection Agency (EPA) in the Houston metropolitan area from Mar 18, 2019, to Dec 31, 2020. Further, we examined the associations between neighborhood-level sociodemographic status and air pollution patterns by linking the low-cost sensor data to EPA environmental justice screening and mapping systems. FINDINGS: We found increased PM levels during ITC fire and pre-COVID-19, and lower PM levels after the COVID-19 lockdown, comparable to observations from the regulatory monitors, with higher variations and a greater number of locations with high PM levels detected. In addition, the environmental justice analysis showed positive associations between higher PM levels and the percentage of minority, low-income population, and demographic index. IMPLICATION: Our study indicates that low-cost sensors provide pollutant measures with higher spatial variations and a better ability to identify hot spots and high peak concentrations. These advantages provide critical information for disaster response and environmental justice studies. SYNOPSIS: We used measurements from a low-cost sensor network for air pollution monitoring and environmental justice analysis to examine the impact of anthropogenic and natural disasters.

Use of Identical INN "Imiglucerase" for Different Drug Products: Impact Analysis of Adverse Events in a Proprietary Global Safety Database.

INTRODUCTION: Approved in 1994 and assigned the International Nonproprietary Name (INN) imiglucerase by the World Health Organization, Cerezyme® (Sanofi Genzyme) is an enzyme replacement therapy used to treat Gaucher disease in > 90 countries. At least two therapies approved outside the USA and the European Union, Abcertin® and Asbroder®, have adopted the identical INN imiglucerase. Both drugs were approved via regulatory pathways not aligned with World Health Organization Similar Biotherapeutic Product guidelines. OBJECTIVE: We analyzed whether the use of the identical INN "imiglucerase" for these drugs impacts adverse event (AE) reporting in the Sanofi Global Safety Database. METHODS: First, we reviewed all imiglucerase individual case safety reports (referred to as cases) including AE data reported between January 2012 and March 2018 that contained Abcertin or Asbroder in the narrative. In a second analysis, we examined cases from Mexico reported between May 2013 and March 2018 to assess changes in imiglucerase reporting following the 2015 approval of Asbroder in Mexico. RESULTS: Fifty-six cases mentioning Asbroder and none mentioning Abcertin were retrieved in the first analysis. Upon close review, the AEs of 45 cases (80.4%) were attributed to Asbroder, one (1.8%) to Cerezyme; the specific drug attribution for the AEs of ten cases (17.9%) could not be determined. In the second analysis, a substantial increase in cases and AEs was observed in the period after Asbroder approval (73 cases with 150 AEs pre-approval vs 132 cases with 333 AEs post-approval). Twenty-three of 132 (17.4%) post-approval cases reported discontinuation of treatment (19 related to Asbroder AEs, and four related to Cerezyme AEs). Infusion-associated reactions occurred in 25/132 cases (17 Asbroder related, six Cerezyme related, two indeterminate). CONCLUSIONS: This analysis demonstrates two potential consequences of identical INN use between Cerezyme and Asbroder: (1) an aggregate safety profile for Cerezyme that includes other products using the identical INN leading to inaccurate pharmacovigilance data and (2) healthcare providers switching, substituting, or potentially assuming interchangeability between the products. Identical INN use without the brand name differentiator may compromise pharmacovigilance data, potentially masking differences in safety profiles between products.

The objective of this study was to assess the consequences of multiple drugs using the identical International Nonproprietary Name (INN) "imiglucerase" on adverse event reporting in the Sanofi Genzyme Global Safety Database. The World Health Organization established the INN system to identify drugs that are made of the same pharmaceutical substance and recommends that different products have distinct INN names. The INN imiglucerase was assigned in 1994 to Cerezyme^® (Sanofi Genzyme), an orphan drug for the treatment of a rare disease known as Gaucher disease. In 2015, Asbroder^® (ISU Abxis) was approved for Gaucher disease in Mexico and has adopted the INN imiglucerase. It was not approved as a biosimilar to Cerezyme. Most importantly, in a significant proportion of the adverse event cases reported, patients received a combination therapy of Asbroder and Cerezyme or Asbroder and "imiglucerase", suggesting that the shared INN may have led to misconceived interchangeability of these products. Such confusion among healthcare providers poses a potentially serious risk to patient safety and health. These results are especially worrisome because they relate to products sharing an INN that were not approved as biosimilars. The findings from this study are also consistent with the view that Cerezyme and Asbroder may have different safety profiles. The implications of drug products having the same INN are discussed in the article as well as recommended solutions. To our knowledge, this is one of the first reports on real-world safety experience with biologics sharing the same INN name.

Pregnancy outcome in women with Gaucher disease type 1 who had unplanned pregnancies during eliglustat clinical trials.

Gaucher disease type 1 (GD1) is an inherited lysosomal storage disorder caused by deficient enzymatic activity of acid ß-glucosidase, resulting in accumulation of its substrate glucosylceramide, leading to debilitating visceral, hematologic, and skeletal manifestations. Women with GD1 are at increased risk for complications during pregnancy, delivery, and postpartum. Treatment with enzyme replacement therapy is generally recommended before and during pregnancy to reduce risks. Eliglustat, an oral substrate-reduction therapy, is a first-line treatment for adults with GD1 adults who have extensive, intermediate, or poor CYP2D6-metabolizer phenotypes (>90% of patients). We report on pregnancy outcomes among women in eliglustat trials who had unplanned pregnancies and female partners of men in the trials. In four phase 2 and 3 eliglustat trials of 393 adults with GD1, women of childbearing potential were required to use contraception, have monthly pregnancy tests, and discontinue eliglustat promptly if pregnant. In phase 2 and 3 trials, 18 women had 19 pregnancies, resulting in 14 healthy infants from 13 pregnancies (one set of twins), three elective terminations, one ectopic pregnancy, one spontaneous abortion, and one in utero death. Median estimated eliglustat exposure duration during pregnancy was 38 days. In phase 1 trials (non-GD1 subjects), one woman had a spontaneous abortion. Partners of 16 eliglustat-treated men with GD1 had 18 pregnancies, all resulting in healthy infants. Eliglustat is not approved during pregnancy due to limited data. Guidelines for clinicians and patients with GD that address use of eliglustat in women of childbearing potential are needed.

Supporting Parents Living in Disadvantaged Areas of Edinburgh to Create a Smoke-Free Home Using Nicotine Replacement Therapy (NRT): A Two-Phase Qualitative Study.

Exposure to second-hand smoke (SHS) in the home is largely associated with socio-economic disadvantage. Disadvantaged parents face specific challenges creating a smoke-free home, often caring for children in accommodation without access to outdoor garden space. Existing smoke-free home interventions largely fail to accommodate these constraints. Innovative approaches are required to address this inequality. In this two-phase study, we engaged with parents living in disadvantaged areas of Edinburgh, Scotland, to explore tailored approaches to creating a smoke-free home and develop and pilot-test an intervention based on their views and preferences. In Phase 1, qualitative interviews with 17 parents recruited from Early Years Centres explored alternative approaches to smoke-free home interventions. In Phase 2, an intervention based on parents' views and preferences was pilot-tested with parents recruited through Early Years and Family Nurse Partnership centres. Seventeen parents took part in an interview to share their views/experiences of the intervention. Data from both study phases were thematically analysed. Phase 1 findings suggested that parents associated nicotine replacement therapy (NRT) with quit attempts but supported the idea of NRT use for temporary abstinence to create a smoke-free home, viewing this as a safer option than using e-cigarettes indoors. In Phase 2, 54 parents expressed an interest in accessing NRT to create a smoke-free home, 32 discussed NRT product choice during a home visit from a smoking adviser, and 20 collected their free NRT prescription from the pharmacy. NRT was used for up to 12 weeks in the home, with ongoing advice available from pharmacy staff. During qualitative interviews (n = 17), parents self-reported successfully creating a smoke-free home, quitting smoking, and reduced cigarette consumption, often exceeding their expectations regarding changes made. The intervention was acceptable to parents, but the multi-step process used to access NRT was cumbersome. Some participants were lost to this process. Parents living in disadvantaged circumstances may benefit from access to NRT for temporary abstinence in the home to assist them to protect their children from SHS exposure. Further research using a more streamlined approach to NRT access is required to determine the feasibility and cost-effectiveness of this approach.

Stigma and Smoking in the Home: Parents' Accounts of Using Nicotine Replacement Therapy to Protect Their Children from Second-Hand Smoke.

Evidence and campaigns highlighting smoking and second-hand smoke risks have significantly reduced smoking prevalence and denormalised smoking in the home in Scotland. However, smoking prevalence remains disproportionally high in socioeconomically disadvantaged groups. Using stigma as a theoretical lens, this article presents a thematic analysis of parents' accounts of attempting to abstain from smoking at home, using nicotine replacement therapy (NRT), in disadvantaged areas of Edinburgh and the Lothians. Smoking stigma, particularly self-stigma, underpinned accounts, with two overarching themes: interplaying barriers and enablers for creation of a smoke-free home and reconceptualisation of the study as an opportunity to quit smoking. Personal motivation to abstain or stop smoking empowered participants to reduce or quit smoking to resist stigma. For those struggling to believe in their ability to stop smoking, stigma led to negative self-labelling. Previously hidden smoking in the home gradually emerged in accounts, suggesting that parents may fear disclosure of smoking in the home in societies where smoking stigma exists. This study suggests that stigma may act both as an enabler and barrier in this group. Reductions in smoking in the home were dependent on self-efficacy and motivations to abstain, and stigma was entwined in these beliefs.

Review of Cerliponase Alfa: Recombinant Human Enzyme Replacement Therapy for Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2.

The objective of this review is to summarize the pharmacology, efficacy, and safety of cerliponase alfa for the treatment of late infantile neuronal ceroid lipofuscinosis type 2 (CLN2). Cerliponase alfa is recombinant human tripeptidyl peptidase 1 enzyme replacement therapy. A phase 1/2 trial established the efficacy and safety of cerliponase alfa for treatment of neuronal ceroid lipofuscinosis type 2. Treatment with intracerebroventricular cerliponase alfa resulted in slower decline of motor and language functions compared with natural history controls. Common adverse events include convulsions, electrocardiography abnormalities, pyrexia, vomiting, and upper respiratory tract infections. Intracerebroventricular device-related adverse events also occur. Cerliponase alfa is the first therapy for neuronal ceroid lipofuscinosis type 2 that targets the disease etiology. Cerliponase alfa is effective in delaying the progression of motor language decline for patients with neuronal ceroid lipofuscinosis type 2.

Long-term adverse event profile from four completed trials of oral eliglustat in adults with Gaucher disease type 1.

BACKGROUND: Eliglustat is a first-line oral treatment for adults with Gaucher disease type 1 who have an extensive, intermediate or poor CYP2D6 metabolizer phenotype (> 90% of patients). Whereas enzyme replacement therapy for Gaucher disease has been widely used for more than two decades, eliglustat has only been in commercial use since 2014. Clinicians and patients want to better understand which adverse events are most commonly associated with eliglustat, as well as their severity, frequency, and duration. METHODS: This pooled analysis of treatment-emergent adverse events combines data from four completed eliglustat clinical trials involving 393 Gaucher disease type 1 patients. It represents 1400 patient-years of eliglustat exposure and a mean treatment duration of 3.6 years (maximum: 9.3 years). RESULTS: Eighty-one percent of patients remained in their respective trial until commercial availability of eliglustat (US patients only) or until trial completion. Nine patients (2.3%) withdrew from their respective trial due to one or more adverse events reported as eliglustat treatment-related; all but one of these events were mild or moderate. Overall, 97% of adverse events were mild or moderate and 86% were reported by the investigator as unrelated to eliglustat treatment. The overall rate of adverse events decreased over time and did not increase with increasing eliglustat dose. We evaluated frequency, duration, and severity of 14 adverse event terms reported at least once as treatment-related in 2% or more of all patients: dyspepsia (5.9%), headache (5.3%), abdominal pain upper (5.1%), dizziness (5.1%), diarrhea (4.6%), nausea (4.6%), arthralgia (3.6%), constipation (3.3%), abdominal pain (2.8%), gastroesophageal reflux disease (2.8%), fatigue (2.8%), palpitations (2.8%), abdominal distension (2.5%), and gastritis (2.3%). For abdominal pain upper, diarrhea, nausea, abdominal pain, and headache events, median duration was less than 14 days. All 14 adverse event terms, except for arthralgia and headache, were reported only once per patient in more than 70% of patients experiencing the event. CONCLUSIONS: This final pooled analysis of treatment-emergent adverse events reinforces the favorable safety profile of eliglustat. The majority of the most frequently reported treatment-related adverse events were mild or moderate, transient, and occurred only once per patient.

Feedback-amplified electrochemical dual-plate boron-doped diamond microtrench detector for flow injection analysis.

An electrochemical flow cell with a boron-doped diamond dual-plate microtrench electrode has been developed and demonstrated for hydroquinone flow injection electroanalysis in phosphate buffer pH 7. Using the electrochemical generator-collector feedback detector improves the sensitivity by one order of magnitude (when compared to a single working electrode detector). The diffusion process is switched from an analyte consuming "external" process to an analyte regenerating "internal" process with benefits in selectivity and sensitivity.

Cavity transport effects in generator-collector electrochemical analysis of nitrobenzene.

Two types of generator-collector electrode systems, (i) a gold-gold interdigitated microband array and (ii) a gold-gold dual-plate microtrench, are compared for nitrobenzene electroanalysis in aerated aqueous 0.1 M NaOH. The complexity of the nitrobenzene reduction in conjunction with the presence of ambient levels of oxygen in the analysis solution provide a challenging problem in which feedback-amplified generator-collector steady state currents provide the analytical signal. In contrast to the more openly accessible geometry of the interdigitated array electrode, where the voltammetric response for nitrobenzene is less well-defined and signals drift, the voltammetric response for the cavity-like microtrench electrode is stable and readily detectable at 1 µM level. Both types of electrode show oxygen-enhanced low concentration collector current responses due to additional feedback via reaction intermediates. The observations are rationalised in terms of a "cavity transport coefficient" which is beneficial in the dual-plate microtrench, where oxygen interference effects are suppressed and the analytical signal is amplified and stabilised.

Generator-collector double electrode systems: a review.

A variety of generator-collector systems are reviewed, from the original rotating ring-disc electrodes developed in the 1950s, to very recent developments using new geometries and microelectrodes. An overview of both theoretical and experimental aspects are given, and the power of these double electrode systems in analytical electrochemistry is illustrated with a range of applications.

The impact of age-related macular degeneration on health status utility values.

PURPOSE: To estimate health status utility values in patients with age-related macular degeneration (ARMD) associated with visual impairments, by using preference-based measures of health. METHOD: This was a cross-sectional study involving patients with unilateral or bilateral ARMD who attended a large teaching hospital. Patients underwent visual tests (near and distant visual acuity [VA] and contrast sensitivity [CS]) and completed health status questionnaires including the Index of Visual Function (VF)-14 and three preference-based measures (the Health Utilities Index Mark III [HUI-3], the EuroQoL Health Questionnaire [EQ-5D], and the Short Form 6D Health Status Questionnaire [SF-6D]) and the time tradeoff (TTO). The mean health status is presented for five groups, defined according to the VA in the better-seeing eye and for four CS groups. RESULTS: Two hundred nine patients were recruited with substantial loss of visual function as obtained by visual tests (mean decimal VA in the better-seeing eye: 0.2) and self-report (mean VF-14 score: 41.5). The mean (+/-SD) utilities were 0.34 +/- 0.28 for HUI-3, 0.66 +/- 0.14 for SF-6D, 0.72 +/- 0.22 for EQ-5D, and 0.64 +/- 0.31 for TTO. The HUI-3 had the highest correlation with VA and CS (0.40 and -0.34), followed by TTO (0.25 and -0.21). Across the VA and CS groups, only HUI3 and TTO had a significant linear trend (P < 0.05). In a regression model with CS and VA as explanatory variables, only the coefficient on CS was statistically significant. CONCLUSIONS: ARMD is associated with a substantial impact on patients' health status, but this was not reflected in two of the generic preference-based measures used. The HUI-3 seems to be the instrument of choice for use in economic evaluations in which community data are needed. It may be more appropriate to base economic models on CS or some combination of CS and VA rather than on VA alone.