Phenytoin and damage to the cerebellum - a systematic review of published cases.

INTRODUCTION: The antiseizure medication phenytoin has been associated with changes in the cerebellum, cerebellar signs, and permanent cerebellar damage. We have systematically reviewed the clinical and radiological features, and their correlation. AREAS COVERED: We identified sixty case reports and case series of the effects of phenytoin on the cerebellum by searching Medline and Embase and relevant reference lists. The reports described 92 [median 1, range 1-5] cases, documented median age 28 [2.7-78] years. Eighty-one cases described one or more clinical sign of ataxia (present in 96%), dysarthria (63%), and nystagmus (70%). The neurological outcome (in 76 cases): 10 (13%) recovered by 12 months; 55 (72%) suffered residual disability; and 11 (14%) died. Median serum phenytoin concentration (48 cases) was 50 (interquartile range 31-66) mg/L; only three values were below 20 mg/L. The radiological findings included cerebellar atrophy in 41 of 61 patients (67%) with at least one scan. EXPERT OPINION: Evidence mainly comes from case reports, and is inevitably biased. Most patients with cerebellar dysfunction have phenytoin concentrations above the reference range. Clinical signs of ataxia can persist without radiological evidence of cerebellar atrophy, and cerebellar atrophy is seen without any clinical evidence of cerebellar dysfunction.

Perfluorocarbon nanomaterials for photodynamic therapy.

Photodynamic therapy (PDT) is a treatment modality in which a photosensitizer is irradiated with light, producing reactive oxygen species, often via energy transfer with oxygen. As it is common for tumors to be hypoxic, methods to deliver photosensitizer and oxygen are desirable. One such approach is the use of perfluorocarbons, molecules in which all C-H bonds are replaced with C-F bonds, to co-deliver oxygen because of the high solubility of gases in perfluorocarbons. This review highlights the benefits and limitations of several fluorinated nanomaterial architectures for use in PDT.

Experimental Perspectives on Direct Visualization of Endosomal Rupture.

Endosomal escape continues to be a limiting factor in the therapeutic use of nanomaterials. Assays to visualize endosomal escape often do not decouple the endosomal/lysosomal disruption from the release of payload into the cytosol. Here, we discuss three approaches to directly probe endosomal/lysosomal rupture: calcein dye dilution, lysosome size quantification and endosome/lysosome membrane integrity visualized with a genetically engineered cell line. We apply the three assays to endosomes/lysosomes ruptured via osmotic pressure and photochemical internalization.

Redox-Responsive Gene Delivery from Perfluorocarbon Nanoemulsions through Cleavable Poly(2-oxazoline) Surfactants.

The clinical utility of emulsions as delivery vehicles is hindered by a dependence on passive release. Stimuli-responsive emulsions overcome this limitation but rely on external triggers or are composed of nanoparticle-stabilized droplets that preclude sizes necessary for biomedical applications. Here, we employ cleavable poly(2-oxazoline) diblock copolymer surfactants to form perfluorocarbon (PFC) nanoemulsions that release cargo upon exposure to glutathione. These surfactants allow for the first example of redox-responsive nanoemulsions in cellulo. A noncovalent fluorous tagging strategy is leveraged to solubilize a GFP plasmid inside the PFC nanoemulsions, whereupon protein expression is achieved selectively when employing a stimuli-responsive surfactant. This work contributes a methodology for non-viral gene delivery and represents a general approach to nanoemulsions that respond to endogenous stimuli.

Fluorous Soluble Cyanine Dyes for Visualizing Perfluorocarbons in Living Systems.

The bioorthogonal nature of perfluorocarbons provides a unique platform for introducing dynamic nano- and microdroplets into cells and organisms. To monitor the localization and deformation of the droplets, fluorous soluble fluorophores that are compatible with standard fluorescent protein markers and applicable to cells, tissues, and small organisms are necessary. Here, we introduce fluorous cyanine dyes that represent the most red-shifted fluorous soluble fluorophores to date. We study the effect of covalently appended fluorous tags on the cyanine scaffold and evaluate the changes in photophysical properties imparted by the fluorous phase. Ultimately, we showcase the utility of the fluorous soluble pentamethine cyanine dye for tracking the localization of perfluorocarbon nanoemulsions in macrophage cells and for measurements of mechanical forces in multicellular spheroids and zebrafish embryonic tissues. These studies demonstrate that the red-shifted cyanine dyes offer spectral flexibility in multiplexed imaging experiments and enhanced precision in force measurements.

Systematic Study of Perfluorocarbon Nanoemulsions Stabilized by Polymer Amphiphiles.

Perfluorocarbon (PFC) nanoemulsions, droplets of fluorous solvent stabilized by surfactants dispersed in water, are simple yet versatile nanomaterials. The orthogonal nature of the fluorous phase promotes the formation of nanoemulsions through a simple, self-assembly process while simultaneously encapsulating fluorous-tagged payloads for various applications. The size, stability, and surface chemistry of PFC nanoemulsions are controlled by the surfactant. Here, we systematically study the effect of the hydrophilic portion of polymer surfactants on PFC nanoemulsions. We find that the hydrophilic block length and identity, the overall polymer hydrophilic/lipophilic balance, and the polymer architecture are all important factors. The ability to modulate these parameters enables control over initial size, stability, payload retention, cellular internalization, and protein adsorption of PFC nanoemulsions. With the insight obtained from this systematic study of polymer amphiphiles stabilizing PFC nanoemulsions, design features required for the optimal material are obtained.

A Reduction-Sensitive Fluorous Fluorogenic Coumarin.

Fluorophores that are sensitive to their environment are useful tools for sensing chemical changes and probing biological systems. Here, we extend responsive fluorophores to the fluorous phase with the synthesis of a reduction-sensitive fluorous-soluble fluorogenic coumarin. We demonstrate that this fluorophore responds to various reducing agents, most notably glutathione, a key biological reductant. The fluorous solubility of this probe allows for its encapsulation into two different fluorous nanomaterials: perfluorocarbon nanoemulsions and fluorous core-shell micelles. The fluorogenic coumarin allows us to study how efficiently these vehicles protect the contents of their interior from the external environment. In the presence of glutathione, we observe different degrees of release for micelles and emulsions. This understanding will help guide future applications of fluorous nanomaterials as drug delivery vehicles.

Liquid laundry detergent capsules (PODS): a review of their composition and mechanisms of toxicity, and of the circumstances, routes, features, and management of exposure.

Introduction: Liquid laundry detergent capsules (also called single-use detergent sacs; laundry pods; laundry packets) have become an increasingly popular household product worldwide. Objectives: To review the composition and mechanisms of toxicity of liquid laundry detergent, capsules, and the circumstances, routes, clinical features (and impact of packaging changes) and management of exposure. Methods: The databases PubMed and EMBASE were searched using the terms: "detergent" and "capsule", "pod", "pac" or "sac" combined with "poison", "ingest", "expos" but not "animal" or "in vitro" or "bacteria". The searches yielded 289 articles, of which 186 were excluded: 38 duplicates, 133 not relevant, 10 abstracts which had been published as a paper and 5 non-English language articles. The bibliographies of relevant articles were hand-searched which yielded 14 additional citations. Searching of abstracts from scientific meetings produced five additional citations. A total of 122 publications were relevant to the objectives of the review. Capsules and composition: Capsules typically contain anionic surfactants (20-35%), non-ionic surfactants (10-20%), propylene glycol (8-20%) and ethanol (2-5%) within a water-soluble polyvinyl alcohol membrane. Mechanisms of toxicity: Non-ionic surfactants are the primary mechanism, though anionic surfactants, ethanol and propylene glycol may also contribute. Circumstances of exposure: The majority (60%) of children are exposed when the capsule is removed from its original container. Routes of exposure: Ingestion is the most common (>85%); ocular (<15%) and dermal (<8%) exposure account for the remainder. Features following ingestion: Features develop in around half of all exposures, though >90% are minor. In those with features, vomiting occurs in some 50%; coughing and drowsiness are reported in <5%. Respiratory depression (<0.5%), central nervous system depression (<0.1%) esophageal or gastric injury (<0.5%), metabolic acidosis and hyperlactatemia (<0.05%) have been reported rarely. Of 17 deaths reported, 13 were adults and nine were suffering from cognitive impairment. Features following ocular exposure: Conjunctivitis, eye irritation and/or eye pain are commonly experienced; corneal injury is less common but complete recovery typically occurs within one week. Features following dermal exposure: Clinically important dermal toxicity seldom occurs, though skin burns can develop in <5% of cases when skin contact is prolonged. Impact of packaging changes on features: The implementation of packaging changes resulted in a fall in the number of exposures and their severity in the United States and in the number in Italy. Management-ingestion: Gut decontamination is not recommended, though small amounts of fluid can be administered orally to rinse out the mouth. Symptomatic and supportive care should be offered to all patients that develop features of toxicity. Supplemental oxygen should be administered for hypoxemia, and bronchodilators for laryngospasm/bronchospasm. Intubation and assisted ventilation may be required if CNS and respiratory depression develop. A chest radiograph should be performed if respiratory features develop. In patients with swallowing difficulties, drooling or oropharyngeal burns, endoscopy should be performed; if substantial mucosal damage is present MRI should be considered. In addition, intravenous fluids will be required if prolonged vomiting or diarrhea occur and acid-base disturbances should be corrected. Management-eye exposure: Thorough irrigation of the eye with sodium chloride 0.9% is required. Instillation of a local anesthetic will reduce discomfort and help more thorough decontamination. Due to the potential for corneal injury, fluorescein should be instilled. If ocular injury is present, the patient should be referred to an ophthalmologist. Management-skin exposure: Skin should be irrigated thoroughly with soap and water, and burns should be treated as a thermal burn. Conclusions: Accidental ingestion usually produces no or only minor features. Very rarely respiratory depression, central nervous system depression, esophageal or gastric injury, hyperlactatemia and metabolic acidosis occur. Ocular exposure results in corneal injury infrequently and skin burns can develop uncommonly following prolonged dermal contact. Of 17 deaths reported, 13 were adults and nine were suffering from cognitive impairment.

Controlling nanoemulsion surface chemistry with poly(2-oxazoline) amphiphiles.

Emulsions are dynamic materials that have been extensively employed within pharmaceutical, food and cosmetic industries. However, their use beyond conventional applications has been hindered by difficulties in surface functionalization, and an inability to selectively control physicochemical properties. Here, we employ custom poly(2-oxazoline) block copolymers to overcome these limitations. We demonstrate that poly(2-oxazoline) copolymers can effectively stabilize nanoscale droplets of hydrocarbon and perfluorocarbon in water. The controlled living polymerization of poly(2-oxazoline)s allows for the incorporation of chemical handles into the surfactants such that covalent modification of the emulsion surface can be performed. Through post-emulsion modification of these new surfactants, we are able to access nanoemulsions with modified surface chemistries, yet consistent sizes. By decoupling size and surface charge, we explore structure-activity relationships involving the cellular uptake of nanoemulsions in both macrophage and non-macrophage cell lines. We conclude that the cellular uptake and cytotoxicity of poly(2-oxazoline)-stabilized droplets can be systematically tuned via chemical modification of emulsion surfaces.

A review of 4652 exposures to liquid laundry detergent capsules reported to the United Kingdom National Poisons Information Service 2008-2018.

Introduction: Liquid laundry detergent capsules contain concentrated liquid laundry detergent in a water-soluble polyvinyl alcohol membrane.Objective: To review 4652 exposures reported to the United Kingdom National Poisons Information Service (NPIS) and to assess the impact of regulatory changes on potential toxicity.Methods: Telephone enquiries to the NPIS and returned questionnaires for these products were analyzed for the period January 2008 to December 2018.Results: Data on 4652 exposures were reported by telephone or questionnaire, of which 95.4% involved children aged ≤5 years. Overall, 1738 of 4594 patients remained asymptomatic (Poisoning Severity Score [PSS] 0), 2729 developed minor (PSS 1) features, 107 suffered moderate features (PSS 2), 19 were graded as severe (PSS 3) and one died. Ingestion was involved in most exposures (n = 4175): vomiting occurred in 46.5%, coughing occurred in 4.3% and central nervous system depression in 3.2%. Nine (0.2%) children were intubated and ventilated. The eye was exposed in 646 cases: 371 (59.8%) suffered conjunctivitis or eye irritation and 21 (3.4%) had keratitis/corneal damage, which persisted in one patient for 9 d. The skin was involved in 364 cases; in 127 (35.5%) minor dermal features developed including erythema, irritation and rash. The most commonly reported features in the 127 cases with PSS ≥2 were vomiting (n = 75), stridor (n = 34), CNS depression (n = 22), keratitis/corneal damage (n = 21), coughing (n = 18), conjunctivitis (n = 13), hypersalivation (n = 12), foaming from the mouth (n = 11) and hypoxemia (n = 11). However, respiratory features (stridor, hypoxemia, bronchospasm, respiratory distress, dyspnea, pulmonary aspiration and tachypnea) were the reason for grading 56 of 127 cases as PSS ≥2.Conclusions: This large data set of 4652 exposures is reassuring in that 97.2% of exposures resulted in no or only minor features, only 107 patients suffered moderate features (PSS 2) and 19 severe (PSS 3) features; one patient died.

Exposures to automatic dishwashing rinse aids reported to the United Kingdom National Poisons Information Service 2008-2016.

OBJECTIVE: To determine the toxicity of rinse aids which are used as drying aids to remove water from crockery. METHODS: Enquiries to the UK National Poisons Information Service (NPIS) were analysed retrospectively for the period January 2008 to December 2016. RESULTS: There were 855 enquiries relating to 828 patients; children aged 5 years or less accounted for 91.1%. Most exposures occurred from ingestion alone (n = 778, 94.0%), but 26 involved ingestion and other routes: 21 with skin contact, 3 with eye contact, and two with both skin and eye contact. There were a further 24 cases of eye contact alone (n = 20, 2.4%) or skin contact alone (n = 3, 0.4%) and a single case of inhalation alone. The World Health Organisation/International Programme on Chemical Safety/European Commission/European Association of Poison Centres and Clinical Toxicologists (WHO/IPCS/EC/EAPCCT) Poisoning severity score [PSS] was known in 824 of the 828 exposures: 425 of 824 (51.6%) patients did not develop clinical features, 381 (46.2%) had a PSS of 1 (minor toxicity), 15 (1.8%) developed moderate (PSS 2) and 3 (0.4%) severe (PSS 3) toxicity. Vomiting was the most common feature, occurring in over a third of all ingestions (n = 286, 35.8%), followed by coughing (n = 73, 9.1%). A higher proportion of adults than children developed clinical features (72.7% of 33 vs 46.0% of 767, p = .0026), although vomiting occurred significantly more frequently amongst children (p = .0315). Of the 25 eye contact cases, eye pain (n = 8) and/or eye irritation (n = 8) were reported, with or without abnormal vision (n = 7); there were two cases of corneal abrasion. Dermal contact rarely produced features; only 4 of 26 patients reported symptoms including skin rash or burning or numbness at the contact site. CONCLUSIONS: Severe clinical features were uncommon following rinse aid exposure; vomiting was the most frequently reported symptom following ingestion.

Fluorous photosensitizers enhance photodynamic therapy with perfluorocarbon nanoemulsions.

Photodynamic therapy (PDT) requires a photosensitizer, light, and oxygen to induce cell death. The majority of efforts to advance PDT focus only on the first two components. Here, we employ perfluorocarbon nanoemulsions to simultaneously deliver oxygen and a photosensitizer. We find that the implementation of fluorous soluble photosensitizers enhances the efficacy of PDT.

Flavylium Polymethine Fluorophores for Near- and Shortwave Infrared Imaging.

Bright fluorophores in the near-infrared and shortwave infrared (SWIR) regions of the electromagnetic spectrum are essential for optical imaging in vivo. In this work, we utilized a 7-dimethylamino flavylium heterocycle to construct a panel of novel red-shifted polymethine dyes, with emission wavelengths from 680 to 1045 nm. Photophysical characterization revealed that the 1- and 3-methine dyes display enhanced photostability and the 5- and 7-methine dyes exhibit exceptional brightness for their respective spectral regions. A micelle formulation of the 7-methine facilitated SWIR imaging in mice. This report presents the first polymethine dye designed and synthesized for SWIR in vivo imaging.

Toxicity resulting from exposure to oven cleaners as reported to the UK National Poisons Information Service (NPIS) from 2009 to 2015.

INTRODUCTION: Oven cleaning products contain corrosive substances, typically sodium or potassium hydroxide. OBJECTIVE: To determine the reported toxicity from exposure to oven cleaning products. METHODS: Telephone enquiries to the UK National Poisons Information Service regarding oven cleaning products were analysed retrospectively for the period January 2009 to December 2015. RESULTS: There were 796 enquiries relating to 780 patients. Ninety-six percent of the products involved in the reported exposures contained sodium hydroxide and/or potassium hydroxide. Ingestion alone (n = 285) or skin contact alone (n = 208) accounted for the majority of cases; inhalation alone (n = 101), eye contact alone (n = 97), and multiple routes of exposure (n = 89) accounted for the remainder. Ninety-five percent of patients exposed by inhalation, 94% exposed dermally and 85% reporting eye exposure, developed features of toxicity. Patients exposed by multiple routes developed symptoms in 70% of cases. Only 103 of the 285 patients ingested oven cleaner directly, whereas 182 patients ingested food they considered to have been contaminated with oven cleaner. In 100 of the 103 direct ingestions where the features and World Health Organisation/International Programme on Chemical Safety/European Commission/European Association of Poison Centres and Clinical Toxicologists Poisoning Severity Score were known, 56 reported symptoms which were minor in 51 cases. The most common features following ingestion were vomiting (n = 26), abdominal pain (n = 22) or pharyngitis (n = 15). Skin burns (n = 91) predominantly involving the hands or arms, occurred in 44% of dermal exposures. Following inhalation, patients frequently developed respiratory features (n = 52) including coughing and chest pain/tightness. Eye pain (n = 43) and conjunctivitis (n = 33) commonly occurred following ocular exposure. CONCLUSIONS: Most (71%) patients exposed to an oven cleaner irrespective of the route of exposure developed features of toxicity, though in most cases only minor features developed; moderate or severe features ensued in ∼4%. Those patients exposed dermally, ophthalmically or by inhalation developed features more frequently (≥85%) than those who ingested a product directly (56%).

CD11b activation suppresses TLR-dependent inflammation and autoimmunity in systemic lupus erythematosus.

Genetic variations in the ITGAM gene (encoding CD11b) strongly associate with risk for systemic lupus erythematosus (SLE). Here we have shown that 3 nonsynonymous ITGAM variants that produce defective CD11b associate with elevated levels of type I interferon (IFN-I) in lupus, suggesting a direct link between reduced CD11b activity and the chronically increased inflammatory status in patients. Treatment with the small-molecule CD11b agonist LA1 led to partial integrin activation, reduced IFN-I responses in WT but not CD11b-deficient mice, and protected lupus-prone MRL/Lpr mice from end-organ injury. CD11b activation reduced TLR-dependent proinflammatory signaling in leukocytes and suppressed IFN-I signaling via an AKT/FOXO3/IFN regulatory factor 3/7 pathway. TLR-stimulated macrophages from CD11B SNP carriers showed increased basal expression of IFN regulatory factor 7 (IRF7) and IFN-ß, as well as increased nuclear exclusion of FOXO3, which was suppressed by LA1-dependent activation of CD11b. This suggests that pharmacologic activation of CD11b could be a potential mechanism for developing SLE therapeutics.

Toxicity from automotive screenwashes reported to the United Kingdom National Poisons Information Service (NPIS) from 2012 to 2015.

BACKGROUND: Automotive screenwashes commonly contain ethylene glycol, methanol, and/or isopropanol; ethanol is also included in many formulations. The concentrations and combinations of each constituent vary considerably between the products. This study was undertaken to investigate the toxicity of automotive screenwashes as reported by telephone to the United Kingdom National Poisons Information Service (NPIS). METHODS: Enquiries to the NPIS relating to automotive screenwashes were analyzed retrospectively for the period January 2012 to December 2015. RESULTS: There were 295 enquiries involving 255 individual exposures. The majority (n = 241, 94.5%) of exposures involved ingestion and 14 of these also involved other routes. Six cases were due to skin contact alone, three to inhalation alone, three to eye contact alone, one to ear exposure alone and another occurred from inhalation and skin contact. Children below 5 years of age accounted for 26% of all ingestions. The identity (and therefore composition) of the screenwash was known with certainty in 124 of 241 ingestions and included methanol in 106 formulations, isopropanol in 72, ethylene glycol in 38, and ethanol in 104. The World Health Organisation/International Programme on Chemical Safety/European Commission/European Association of Poison Centres and Clinical Toxicologists Poisoning Severity Score was known in 235 of 241 cases of ingestion: most patients were asymptomatic (n = 169, 71.9%), but 59 (25.1%) developed minor (PSS 1), six (2.6%) moderate (PSS 2), and one patient severe (PSS 3) features; this patient later died. Nausea (n = 10), vomiting (n = 11), abdominal pain (n = 10), metabolic acidosis (n = 8) and raised anion gap (n = 8) were reported most commonly after ingestion. CONCLUSIONS: Most patients (71.9%) ingesting automotive screenwash did not develop features. The implication is that the amount of screenwash ingested was very small. Skin and eye exposure produced either no features or only minor toxicity.

The impact of an international initiative on exposures to liquid laundry detergent capsules reported to the United Kingdom National Poisons Information Service between 2008 and 2015.

INTRODUCTION: Although the majority of those exposed to liquid laundry detergent capsules remain asymptomatic or suffer only minor clinical features after exposure, a small proportion develop central nervous system depression, stridor, pulmonary aspiration and/or airway burns following ingestion or conjunctivitis and corneal ulceration following eye exposure. As a consequence, the International Association for Soaps, Detergents and Maintenance Products (AISE) established a Product Stewardship Programme in Europe, requiring that safety measures be implemented to reduce the visibility of, and restrict access to, these detergent capsules by small children. Implementation occurred in the United Kingdom over several months during the first half of 2013. OBJECTIVE: This study investigated whether the AISE Programme had an impact on the number and severity of exposures reported to the United Kingdom National Poisons Information Service. METHODS: Telephone enquiries to the National Poisons Information Service relating to liquid laundry detergent capsules were analysed for the period January 2008 to December 2015. RESULTS: While there was a significant difference (p = 0.0002) between the mean number of annual exposures (469.4) reported between 2008 and 2012 and the mean number reported between 2014 and 2015 (403.5), the number of exposures was decreasing steadily prior to implementation of the Programme in 2013, which did not impact this fall from 2013 onwards. In addition, the number of exposures per million units sold was not impacted by the Programme. There was no significant difference (p = 0.68) between the mean number of exposures (11.8) with PSS ≥2 reported between 2008 and 2012 and the mean number (13.0) reported between 2014 and 2015. Although there was a 28.7% decrease between 2010-2012 and 2014-2015 in the number of exposures with PSS ≥2 per million units sold, this decrease was not statistically significant (p = 0.18). CONCLUSION: There is no evidence that the Product Stewardship Programme had a beneficial impact on the number of exposures reported to the National Poisons Information Service or their severity.

Exposures to traditional automatic dishwashing tablets and a comparison with exposures to soluble film tablets reported to the United Kingdom National Poisons Information Service 2008-2015.

INTRODUCTION: Traditional automatic dishwashing tablets are contained within an external wrapper that requires removal prior to use. OBJECTIVE: To determine the toxicity of traditional tablets and to compare this with our previously reported experience of soluble film dishwashing tablets. METHODS: Telephone enquiries regarding traditional tablets were analysed retrospectively for the period January 2008 to December 2015. RESULTS: Traditional tablets: There were 503 enquiries relating to 492 patients who had been exposed to a traditional tablet. Most involved children aged 5 years or less (87.4%). The majority (78.6%) of patients did not develop symptoms after exposure; 21.1% developed minor (PSS 1) symptoms while one patient developed moderate features. Exposure occurred predominantly as a result of ingestion (n = 476, 96.7%); the most common feature in symptomatic patients (n = 99, 20.8%) was vomiting (70 [14.7%] cases). Significantly (p < 0.0001) more adults (44.9% of 49 adults; 95% CI = 31.9-58.7) were reported with features than children (18.2% of 434; 95% CI = 14.9-22.1). There were five cases of eye contact which resulted in eye pain in two patients and eye irritation in another. Only one of 11 patients exposed dermally developed features (a rash around the mouth). Comparison with soluble film exposures: The percentage of patients that were reported with clinical symptoms following ingestion of a soluble film dishwashing tablet (31.7% of 473 patients; 95% CI = 27.7-36.0) was significantly greater (p < 0.0001) than that for a traditional tablet (20.9% of 483 patients; 95% CI = 17.5-24.8). Vomiting was the most commonly reported feature and occurred significantly (p < 0.0001) more frequently amongst patients who had ingested a soluble film tablet (25.5%; 95% CI = 21.8-29.6) than a traditional tablet (14.7%; 95% CI = 11.8-18.1). CONCLUSIONS: Exposure to both traditional and soluble film tablets only rarely produced clinically significant symptoms (PSS ≥2). However, ingestion of a soluble film tablet was significantly more likely to result in clinical features than ingestion of a traditional tablet.

Toxicity of soluble film automatic dishwashing products as reported to the United Kingdom National Poisons Information Service 2008-2015.

INTRODUCTION: Soluble film automatic dishwashing tablets, unlike their traditional counterparts, require no removal from an outer protective wrapper prior to use. Instead, the tablets are enclosed by a water-soluble polyvinyl alcohol film and are loaded straight into the dishwashing machine. They most commonly contain a source of hydrogen peroxide (often as sodium percarbonate) and non-ionic surfactants. Other constituents in some formulations include sodium carbonate, sodium tripolyphosphate and sodium silicate, which reduce water hardness. The pH once dissolved in water is alkaline. OBJECTIVE: To determine the toxicity from exposure to soluble film automatic dishwashing tablets. METHODS: Telephone enquiries to the United Kingdom National Poisons Information Service regarding soluble film automatic dishwashing products were analysed retrospectively for the period January 2008 to December 2015. RESULTS: There were 498 enquiries relating to 488 patients. Almost all exposures occurred in the home (98.4%) and involved children aged ≤5 years (92.8%). Exposure occurred mainly as a result of ingestion alone (n = 470, 96.3%); eye contact alone (n = 9, 1.8%) and exposures involving multiple routes (ingestion with skin or eye contact; n = 9, 1.8%) made up the remaining cases. The majority of patients were asymptomatic following exposure (n = 325, 67.4%). The most common feature following ingestion was vomiting which occurred in 121 of 474 cases (25.5%) where clinical data were available. Nausea (n = 8, 1.7%) and coughing (n = 6, 1.3%) were also reported; three patients developed stomatitis and another five developed a rash where ingestion alone was considered to be the sole route of exposure. Ocular exposure to the tablet contents resulted in blurred vision, eye pain or conjunctivitis in seven of ten patients. CONCLUSION: Ingestion of a soluble film automatic dishwashing tablet rarely resulted in clinically significant symptoms, which is surprising given the potential hazard of the ingredients. Hence, it seems probable that the amount of material actually ingested was very small or that most was spat out.

Readability statistics of patient information leaflets in a Speech and Language Therapy Department.

BACKGROUND: Information leaflets are commonly used in Speech and Language Therapy Departments. Despite widespread use, they can be of variable quality. AIMS: To revise current departmental leaflets using the National Health Service (NHS) Toolkit for Producing Patient Information and to test the effect that this has on the readability scores of the text. METHODS & PROCEDURES: Twenty existing leaflets were revised with the help of the NHS Toolkit for Producing Patient Information. Readability statistics were calculated for each leaflet before and after revision. OUTCOMES & RESULTS: The mean Flesch Reading Ease (FRE) score and the Flesch-Kincaid Reading Grade Level (FKRGL) were significantly better in the revised leaflets (p<0.01 and <0.01, respectively). The variability of readability outcome measures was lower in the revised group. Only 25% of the original leaflets met recommended levels of readability, while 75% of the revised leaflets met these standards. CONCLUSIONS: Readability is a vital component to consider in the production of information leaflets. Following simple guidelines on the production of leaflets for patients considerably improves their quality.