SMS-based interventions for improving child and adolescent vaccine coverage and timeliness: a systematic review.

BACKGROUND: The aim of this review was to investigate the impact of short message service (SMS)-based interventions on childhood and adolescent vaccine coverage and timeliness. METHODS: A pre-defined search strategy was used to identify all relevant publications up until July 2022 from electronic databases. Reports of randomised trials written in English and involving children and adolescents less than 18 years old were included. The review was conducted in accordance with PRISMA guidelines. RESULTS: Thirty randomised trials were identified. Most trials were conducted in high-income countries. There was marked heterogeneity between studies. SMS-based interventions were associated with small to moderate improvements in vaccine coverage and timeliness compared to no SMS reminder. Reminders with embedded education or which were combined with monetary incentives performed better than simple reminders in some settings. CONCLUSION: Some SMS-based interventions appear effective for improving child vaccine coverage and timeliness in some settings. Future studies should focus on identifying which features of SMS-based strategies, including the message content and timing, are determinants of effectiveness.

Does social-norm messaging influence expected satiety and ideal portion-size selection?

A person's perception of how long a food will stave off hunger (expected satiety) and the ideal amount to consume (ideal portion size) are both influenced by food-to-mealtime norms. Here, we examine whether social norms can modulate this effect, in three experimental studies. In study 1 (n = 235) participants were exposed to a social norm suggesting most people enjoyed consuming pasta for breakfast. There was a main effect of food-to-mealtime congruence for expected satiety and ideal portion size (p < 0.001) - participants selected a smaller portion of pasta for breakfast (vs. lunch) - but there were no other main effects/interactions (p ≥ 0.15). Study 2 (n = 200) followed the same approach as study 1, but sought to examine whether the typical volume of food consumed at breakfast and lunch needed to be controlled. Again, there was a main effect of congruence (the same pattern) (p ≤ 0.02) but no other main effects/interactions (p ≥ 0.73). Study 3 (n = 208) followed the same approach as study 2, but the social-norm message was changed to suggest that most people who eat pasta for breakfast found it effectively reduced their hunger. Again, there was a main effect of congruence (the same pattern) (p < 0.001) but no other main effects/interaction (p ≥ 0.26). These studies provide further evidence for the food-to-mealtime effect, but do not provide any evidence that a single, simple social-norm statement can modulate expected satiety or ideal portion size, or interact with the food-to-mealtime effect.

Core protocol for the adaptive Platform Trial In COVID-19 Vaccine priming and BOOsting (PICOBOO).

BACKGROUND: The need for coronavirus 2019 (COVID-19) vaccination in different age groups and populations is a subject of great uncertainty and an ongoing global debate. Critical knowledge gaps regarding COVID-19 vaccination include the duration of protection offered by different priming and booster vaccination regimens in different populations, including homologous or heterologous schedules; how vaccination impacts key elements of the immune system; how this is modified by prior or subsequent exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and future variants; and how immune responses correlate with protection against infection and disease, including antibodies and effector and T cell central memory. METHODS: The Platform Trial In COVID-19 priming and BOOsting (PICOBOO) is a multi-site, multi-arm, Bayesian, adaptive, randomised controlled platform trial. PICOBOO will expeditiously generate and translate high-quality evidence of the immunogenicity, reactogenicity and cross-protection of different COVID-19 priming and booster vaccination strategies against SARS-CoV-2 and its variants/subvariants, specific to the Australian context. While the platform is designed to be vaccine agnostic, participants will be randomised to one of three vaccines at trial commencement, including Pfizer's Comirnaty, Moderna's Spikevax or Novavax's Nuvaxovid COVID-19 vaccine. The protocol structure specifying PICOBOO is modular and hierarchical. Here, we describe the Core Protocol, which outlines the trial processes applicable to all study participants included in the platform trial. DISCUSSION: PICOBOO is the first adaptive platform trial evaluating different COVID-19 priming and booster vaccination strategies in Australia, and one of the few established internationally, that is designed to generate high-quality evidence to inform immunisation practice and policy. The modular, hierarchical protocol structure is intended to standardise outcomes, endpoints, data collection and other study processes for nested substudies included in the trial platform and to minimise duplication. It is anticipated that this flexible trial structure will enable investigators to respond with agility to new research questions as they arise, such as the utility of new vaccines (such as bivalent, or SARS-CoV-2 variant-specific vaccines) as they become available for use. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12622000238774. Registered on 10 February 2022.

Portions selected to stave off hunger are reduced when food is presented in an 'unusual' food-to-mealtime context: An implication for implicit satiety drivers.

Research suggests that the role of expected satiety in influencing portion-size selection is reduced when food is presented in unusual food-to-mealtime contexts; however, the underlying mechanism has not been explored. Other research has revealed that different implicit satiety drivers (e.g., to stop momentary hunger or obtain complete fullness) are associated with different perceived levels of stomach fullness, portion-size selections and can change on instruction. The current study explored whether changes in expected satiety and ideal portions in congruous vs incongruous contexts can be explained by changes in implicit satiety drivers. Another aim was to investigate a previous exploratory finding suggesting that portions selected to stave off hunger are reduced when foods are presented in unusual food-to-mealtime contexts. At two trials (breakfast/lunch), participants (n = 40) selected a portion of typical lunch (pasta) and breakfast (porridge) foods via a psychophysical computer-based method 1) to stave off hunger for 5 h, and 2) as an ideal portion. Participants also indicated their perceived level of stomach fullness associated with 1) each portion, and 2) five implicit satiety drivers. Results revealed that a smaller average portion was selected to stave off hunger in incongruous (vs congruous) food-to-mealtime contexts (531 ± 229 vs 575 ± 236 kcal) (p = 0.008). This suggests that expected satiety is influenced by momentary context; foods are perceived to be more satiating when consumed in unusual (vs usual) contexts. Results also showed that implicit satiety drivers are malleable in regard to the portion size associated with a perceived level of stomach fullness and that this can vary contextually. These findings provide initial evidence to explain the psychological mechanism underlying the contextual differences observed in portion-size selections. Future work should explore longer-term impacts of consuming foods in unusual contexts.

Current appetite influences relative differences in the expected satiety of foods for momentary, but not hypothetical, expected satiety assessments.

Research has shown that expected satiety is highly associated with portion-size selection and can vary (kcal-for-kcal) significantly between foods. However, research has not adequately investigated whether current appetite influences relative differences in the expected satiety of foods. This is important to explore to better understand how current motivational state influences food choice and portion selection. This study used 'hypothetical' and 'momentary' expected-satiety assessments to understand whether methods requiring a reflection on current motivational state [momentary] versus more hypothetical considerations when assessing expected satiety can influence the interpretation of results. It was hypothesised that current appetite would only influence relative differences in expected satiety between foods for momentary, but not hypothetical, expected satiety assessments. Participants (n = 54) were shown images of twelve foods, once when hungry and once when full. In each case, they selected a portion for each food to 1) match the expected satiety of a fixed-portion 'standard' food [hypothetical], and 2) stave off hunger until their next meal [momentary]. Results showed that the relative between-food comparison of expected satiety was stable for hypothetical (p=.73) but not momentary assessments (p<.001) suggesting that while current motivational state may influence food choice and portion selection in the moment, more generalised comparisons of the satiating abilities of foods (learned over a longer period) remain stable. This is important 1) for methods in future studies, as immediate dietary intake does not appear to influence hypothetical expected satiety, thus dietary control is not necessary before participants undertake these assessments, and 2) as it confirms that difficulties associated with dietary regulation may not be due to inaccurate hypothetical judgements about foods, but instead appear to be influenced by contextual nuances that occur in the moment.

Eating rate and food intake are reduced when a food is presented in an 'unusual' meal context.

Research has shown that 1) the slower a food is eaten the less food is consumed overall, and 2) context affects portion selection. This study aimed to explore whether eating rate and food intake are influenced by consuming food in 'usual' vs 'unusual' mealtime contexts. Furthermore, this study aimed to identify whether mealtime-specific appropriateness and previous consumption frequency corresponded with differences in eating rate and food intake between contexts. Seventy-eight participants were served either cheese and tomato pasta (a typical lunch food) or porridge with milk and honey (a typical breakfast food) ad libitum at both breakfast and lunch on separate days. Results showed that eating rate was slower (60.7 vs 71.2 g/min, p < 0.001) and less food was consumed (404.1 vs 543.2 g, p < 0.001) when participants ate cheese and tomato pasta at breakfast compared to at lunch. However, no significant differences in eating rate (54.6 vs 56.4 g/min, p = 0.75) or food intake (423.7 vs 437.7 g, p = 0.88) were found between mealtimes for porridge with milk and honey. Furthermore, differences in eating rate and food intake between contexts were not associated with differences in mealtime-specific appropriateness or previous consumption frequency. These results suggest that eating rate and ad libitum food intake are influenced by the congruency of the food-to-mealtime context; however, this effect is not associated with mealtime-specific appropriateness or previous consumption of the food. Further research should explore the implications of introducing foods at unusual mealtimes in relation to strategies for weight management.

The influence of expected satiety on portion size selection is reduced when food is presented in an 'unusual' meal context.

Research shows that expected satiety is highly correlated with ideal portion size, however this correspondence has not been explored when a food is presented in an 'unusual' (incongruous) meal context. This study's aim was to explore whether expected satiety influences portion selection to the same extent in both congruous and incongruous meal contexts. Forty participants completed two trials (one at breakfast and one at lunch) on separate days in a randomised counterbalanced order. They completed measures of expected satiety and ideal portion size for four typical breakfast foods and four typical lunch foods, using a bespoke computer program. Our results showed a significant difference between expected satiety and ideal portion size for lunch foods presented at breakfast time (an incongruous meal context; t(39) = 2.95, p = 0.02). There was no significant difference between expected satiety and ideal portion size in the other incongruous meal context (breakfast foods at lunch; t(39) = 2.10, p = 0.17) or in congruous meal contexts (breakfast foods at breakfast time, lunch foods at lunch time; both t(39) ≤ -0.15, p > 0.999). These results suggest that expected satiety does not have as strong an influence on portion selection when food is presented in an unusual context. Furthermore, in such contexts, smaller portions were selected 1) to stave off hunger until the next meal and 2) as ideal portions compared to in more usual meal contexts. Research is warranted to explore this finding further to understand its implications for weight management.

Burden of non-melanoma skin cancer attributable to occupational sun exposure in Canada.

PURPOSE: Outdoor workers are exposed daily to solar ultraviolet radiation, an important contributor in the development of non-melanoma skin cancer. This study aimed to quantify the health burden of non-melanoma skin cancers among outdoor workers in Canada. METHODS: Solar ultraviolet radiation exposure and estimates of exposure levels were applied to employment information from Canada census data to determine the exposed population in the risk exposure period (1961-2001). Risk estimates were drawn from meta-analyses selected based on quality and relevance to the current study. Population-attributable fractions were calculated using Levin's equation and attributable cases were estimated based on incidence data reported by the Canadian Cancer Society. RESULTS: In 2011, 6.31% (4556 cases) of non-melanoma skin cancer cases were estimated to be attributable to occupational exposure to solar ultraviolet radiation. The majority of these cases occurred in men in the agriculture or construction industries. CONCLUSIONS: These estimates of the burden of non-melanoma skin cancer in Canada identify the need for further prevention efforts, particularly in agriculture and construction. Introducing workplace sun safety measures could be an important area for policy development.

Risk factors and mitigation of influenza among Indigenous children in Australia, Canada, United States, and New Zealand: a scoping review.

AIM: This review considers prominent risk factors and mitigation strategies of influenza among Indigenous children. METHODS: Seven electronic databases were searched from the period of 2004-2017 to locate articles discussing influenza among Indigenous children in the developed circumpolar nations of Australia, Canada, United States, and New Zealand. Articles selected for inclusion discussed influenza among Indigenous children as either individuals or as a part of a community. Ancestry searches of articles meeting the review criteria were also undertaken to discern seminal research in this topic area. RESULTS: From the 39 primary research studies included, marked risk factors and mitigation strategies of influenza among Indigenous children were identified using inductive analysis. Notable risk factors included age under 2 years, cigarette smoke exposure, presence of a chronic illness, and crowded living conditions. Successful mitigation of influenza for Indigenous children included strategies to improve vaccine coverage, provision of health education, and policy change. CONCLUSION: In the past, the impact of influenza upon Indigenous communities has been devastating for both children and their families. By utilizing existing public health infrastructure and collaborating with culturally unique Indigenous groups, preventive action for Indigenous children at significant risk of contracting influenza can be realized.

Solar particle event storm shelter requirements for missions beyond low Earth orbit.

Protecting spacecraft crews from energetic space radiations that pose both chronic and acute health risks is a critical issue for future missions beyond low Earth orbit (LEO). Chronic health risks are possible from both galactic cosmic ray and solar energetic particle event (SPE) exposures. However, SPE exposures also can pose significant short term risks including, if dose levels are high enough, acute radiation syndrome effects that can be mission- or life-threatening. In order to address the reduction of short term risks to spaceflight crews from SPEs, we have developed recommendations to NASA for a design-standard SPE to be used as the basis for evaluating the adequacy of proposed radiation shelters for cislunar missions beyond LEO. Four SPE protection requirements for habitats are proposed: (1) a blood-forming-organ limit of 250 mGy-equivalent for the design SPE; (2) a design reference SPE environment equivalent to the sum of the proton spectra during the October 1989 event series; (3) any necessary assembly of the protection system must be completed within 30 min of event onset; and (4) space protection systems must be designed to ensure that astronaut radiation exposures follow the ALARA (As Low As Reasonably Achievable) principle.

On the origin and impact of mesenchymal stem cell heterogeneity: new insights and emerging tools for single cell analysis.

Mesenchymal stem cells (MSCs) display substantial cell-to-cell variation. This heterogeneity manifests among donors, among tissue sources, and within cell populations. Such pervasive variability complicates the use of MSCs in regenerative applications and may limit their therapeutic efficacy. Most conventional assays measure MSC properties in bulk and, as a consequence, mask this cell-to-cell variation. Recent studies have identified extensive variability amongst and within clonal MSC populations, in dimensions including functional differentiation capacity, molecular state (e.g. epigenetic, transcriptomic, and proteomic status), and biophysical properties. While the origins of these variations remain to be elucidated, potential mechanisms include in vivo micro-anatomical heterogeneity, epigenetic bistability, and transcriptional fluctuations. Emerging tools for single cell analysis of MSC gene and protein expression may yield further insight into the mechanisms and implications of single cell variation amongst these cells, and ultimately improve the clinical utility of MSCs in tissue engineering and regenerative medicine applications. This review outlines the dimensions across which MSC heterogeneity is present, defines some of the known mechanisms that govern this heterogeneity, and highlights emerging technologies that may further refine our understanding and improve our clinical application of this unique cell type.

Characteristics of work-related fatal and hospitalised injuries not captured in workers' compensation data.

OBJECTIVES: (1) To identify work-related fatal and non-fatal hospitalised injuries using multiple data sources, (2) to compare case-ascertainment from external data sources with accepted workers' compensation claims and (3) to investigate the characteristics of work-related fatal and hospitalised injuries not captured by workers' compensation. METHODS: Work-related fatal injuries were ascertained from vital statistics, coroners and hospital discharge databases using payment and diagnosis codes and injury and work descriptions; and work-related (non-fatal) injuries were ascertained from the hospital discharge database using admission, diagnosis and payment codes. Injuries for British Columbia residents aged 15-64 years from 1991 to 2009 ascertained from the above external data sources were compared to accepted workers' compensation claims using per cent captured, validity analyses and logistic regression. RESULTS: The majority of work-related fatal injuries identified in the coroners data (83%) and the majority of work-related hospitalised injuries (95%) were captured as an accepted workers' compensation claim. A work-related coroner report was a positive predictor (88%), and the responsibility of payment field in the hospital discharge record a sensitive indicator (94%), for a workers' compensation claim. Injuries not captured by workers' compensation were associated with female gender, type of work (natural resources and other unspecified work) and injury diagnosis (eg, airway-related, dislocations and undetermined/unknown injury). CONCLUSIONS: Some work-related injuries captured by external data sources were not found in workers' compensation data in British Columbia. This may be the result of capturing injuries or workers that are ineligible for workers' compensation, or the result of injuries that go unreported to the compensation system. Hospital discharge records and coroner reports may provide opportunities to identify workers (or family members) with an unreported work-related injury and to provide them with information for submitting a workers' compensation claim.

Nitazoxanide for the treatment of infectious diarrhoea in the Northern Territory, Australia 2007-2012.

INTRODUCTION: Australian Indigenous children suffer a high burden of diarrhoeal disease. Nitazoxanide is an antimicrobial that has been shown to be effective against a broad range of enteropathogens. To date, its use has not been reported in the tropical Top End (northernmost part) of the Northern Territory, Australia. The objective was to describe the use of nitazoxanide at the Royal Darwin Hospital, Northern Territory, and to assess any association with the time to resolution of diarrhoea. METHODS: Eligible children (≤13 years) were identified from dispensary records as having been prescribed nitazoxanide during the audit period, 1 July 2007 to 31 March 2012. Patient demographics, symptoms, diarrheal aetiology, treatment details and clinical outcomes were obtained by chart review. RESULTS: Twenty-eight children were treated with nitazoxanide, mostly for Cryptosporidium infection associated with prolonged diarrhoea. Dehydration was evident in 27 (96%) children on admission, and 11 (41%) were underweight. Diarrhoeal duration prior to treatment was 11.5 days (6.5 days pre- and 5 days post-admission). For children ≥12 months, nitazoxanide was prescribed according to guidelines stipulated by the Centers for Disease Control and Prevention (CDC). Resolution of diarrhoea occurred a median of 2.4 days (IQR: 1.4-7.3) after starting treatment. An increase in weight for length at discharge was found for all children. CONCLUSIONS: Prompt resolution of diarrhoea without adverse outcomes suggests nitazoxanide may be an effective treatment for Cryptosporidium infection in this setting. Its role in the treatment of other causes of infectious diarrhoea needs further investigation. Randomised trials will further direct its use and determine optimal dosing regimens.

The impact of continuous haemofiltration with high-volume fluid exchange during cardiopulmonary bypass surgery on the recovery of patients with impaired renal function: a pilot randomised trial.

BACKGROUND: There is widespread variability in clinical practice within cardiac surgery units worldwide on the use of haemofiltration. The clinical impact and safety of this modality is, however, unknown. OBJECTIVES: The primary pilot trial objectives were as follows: to assess the feasibility of randomising 60 patients with impaired kidney function undergoing on-pump coronary artery bypass graft (CABG) surgery within 6 months; to assess the suitability and reliability of our chosen outcome measures; to explore issues that may impact on recruitment into a definitive trial; and to undertake an exploratory economic evaluation. DESIGN: A pilot, single-centre, open-label randomised trial. SETTING: Liverpool Heart and Chest Hospital NHS Foundation Trust between November 2010 and March 2012. PARTICIPANTS: Men and women, aged > 18 years of age, undergoing on-pump CABG surgery, who had pre-operative impaired kidney function indicated by an estimated glomerular filtration rate (eGFR) of < 60 ml/minute adjusted for 1.73 m(2) of body surface area. INTERVENTIONS: Group 1: patients who received haemofiltration during bypass (experimental group). Group 2: patients who did not receive haemofiltration during bypass (control group). MAIN OUTCOME MEASURES: (1) Feasibility outcome measures: barriers to recruitment to a larger trial were documented as observations made during the recruitment period of the trial. Reliability of data collection methods was monitored using a 13-point case record form validation check for data entry against the patient clinical notes and the trial database. (2) The main clinical outcomes were frequency of intensive care unit (ICU) stay of duration > 3 days and the length of ICU stay days. (3) Other clinical outcomes were the need for postoperative haemofiltration in the ICU, mechanical ventilation time, hospital stay, composite of outcome of unfavourable perioperative events and eGFR values at 6 weeks' follow-up. (4) Secondary health economic feasibility outcomes. RESULTS: Recruitment into the pilot trial was from 21 November 2010 to 30 March 2012. Thirty-seven eligible patients were consented and successfully randomised into the trial arms (30%). The main issues impacting on recruitment were the high volume of off-pump CABG surgery within the centre; recruitment being restricted to research nurses' working hours of the week; issues arising associated with the screening process for identifying prospective eligible patients based on eGFR values; protocol deviations/treatment crossovers; and unexpected outbreaks of pandemic influenza and other infectious conditions. The data collection process was sufficiently robust, with few errors detected. The length of ICU stay days was deemed a suitable primary outcome. There was an overall trend towards reduction in the length of ICU stay for patients who were given intraoperative haemofiltration, more so for those with diabetes. The economic evaluation estimated that the incremental costs per person were £1744 lower for the intraoperative haemofiltration group, while the incremental benefits per person increased by 0.11. CONCLUSION: Given sufficient resources and broadening of the inclusion criteria, the recruitment into a larger multicentre trial is feasible and may demonstrate potential clinical and cost benefits of using intraoperative haemofiltration in this group of patients. However, owing to the small sample size in this pilot trial, no firm conclusions can be drawn from the findings at this stage. The outcomes of this pilot study are very encouraging and suggest that it is feasible to design a continuous superiority trial with the length of ICU stay days or time to tracheal extubation as the primary outcome measure, provided that guidelines for avoiding bias are implemented. An alternative primary outcome measure that avoids bias is mortality. The inclusion criteria should also be widened to include all cardiac surgery patients with impaired renal function. TRIAL REGISTRATION: ISRCTN49513454. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 49. See the HTA programme website for further project information.

Population-based surveillance of asthma among workers in British Columbia, Canada.

INTRODUCTION: Population-based health databases were used for the surveillance of asthma among workers in British Columbia for the period 1999 to 2003. The purpose was to identify high-risk groups of workers with asthma for further investigation, education and prevention. METHODS: Workers were identified using an employer-paid health premium field in the provincial health registry, and were linked to their physician visit, hospitalization, workers' compensation and pharmaceutical records; asthma cases were defined by the presence of an asthma diagnosis (International Classification of Diseases [ICD]-9-493) in these health records. Workers were assigned to an ''at-risk'' exposure group based on their industry of employment. RESULTS: For males, significantly higher asthma rates were observed for workers in the Utilities, Transport/Warehousing, Wood and Paper Manufacturing (Sawmills), Health Care/Social Assistance and Education industries. For females, significantly higher rates were found for those working in the Waste Management/Remediation and Health Care/Social Assistance industries. CONCLUSION: The data confirm a high prevalence of active asthma in the working population of British Columbia, and in particular, higher rates among females compared to males and in industries with known respiratory sensitizers such as dust and chemical exposures.

Elemental imaging of MRI contrast agents: benchmarking of LA-ICP-MS to MRI.

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been used to map the spatial distribution of magnetic resonance imaging (MRI) contrast agents (Gd-based) in histological sections in order to explore synergies with in vivo MRI. Images from respective techniques are presented for two separate studies namely (1) convection enhanced delivery of a Gd nanocomplex (developmental therapeutic) into rat brain and (2) convection enhanced delivery, with co-infusion of Magnevist (commercial Gd contrast agent) and Carboplatin (chemotherapy drug), into pig brain. The LA technique was shown to be a powerful compliment to MRI not only in offering improved sensitivity, spatial resolution and signal quantitation but also in giving added value regarding the fate of administered agents (Gd and Pt agents). Furthermore simultaneous measurement of Fe enabled assignment of an anomalous contrast enhancement region in rat brain to haemorrhage at the infusion site.

Chemical speciation studies on DU contaminated soils using flow field flow fractionation linked to inductively coupled plasma mass spectrometry (FlFFF-ICP-MS).

Flow field flow fractionation (FlFFF) in combination with inductively coupled plasma mass spectrometry (ICP-MS) was used to study the chemical speciation of U and trace metals in depleted uranium (DU) contaminated soils. A chemical extraction procedure using sodium pyrophosphate, followed by isolation of humic and fulvic substances was applied to two dissimilar DU contaminated sample types (a sandy soil and a clay-rich soil), in addition to a control soil. The sodium pyrophosphate fractions of the firing range soils (Eskmeals and Kirkcudbright) were found to contain over 50% of the total U (measured after aqua regia digestion), compared to approximately 10% for the control soil. This implies that the soils from the contaminated sites contained a large proportion of the U within more easily mobile soil fractions. Humic and fulvic acid fractions each gave characteristic peak maxima for analytes of interest (Mn, Fe, Cu, Zn, Pb and U), with the fulvic acid fraction eluting at a smaller diameter (approximately 2.1 nm on average) than the humic fraction (approximately 2.4 nm on average). DU in the fulvic acid fraction gave a bimodal peak, not apparent for other trace elements investigated, including natural U. This implies that DU interacts with the fulvic acid fraction in a different way to all other elements studied.

Nickel skin levels in different occupations and an estimate of the threshold for reacting to a single open application of nickel in nickel-allergic subjects.

BACKGROUND: Nickel is a frequent allergen throughout the world. However, the extent to which nickel is relevant as an occupational contact allergen as opposed to being simply a reflection of jewellery exposure has been unclear. Some thresholds for cutaneous nickel exposure to induce a dermatitis reaction in nickel-allergic individuals have been defined. Over recent years it has become possible to measure accurately the quantity of nickel on the skin of individuals in a number of occupations. OBJECTIVES: To measure the quantities of nickel on the skin of the fingers in workers employed in occupations for which nickel has been suspected as a contact allergen. To define the threshold for a dermatitis reaction after the single application of a quantity of nickel to the skin of nickel-allergic individuals when read at 2days. METHODS: We employed the 'finger immersion' technique for sample collection and induction coupled plasma mass spectrometry for the nickel measurement. Nickel platers, cashiers, sales assistants, caterers, healthcare assistants, office workers, dental nurses and hairdressers were studied (five in each group except for seven cashiers). A correction was made for the fact that the finger immersion method underestimates the amount of nickel on the fingertip. The threshold for reactivity to a single application of nickel was studied by the application of various concentrations of nickel (µgcm(-2) ) [0·05 (two subjects), 0·5 (two subjects), 2·5 (three subjects), 5·0 (21 subjects), 15 (19 subjects), 30 (19 subjects) and 45 (18 subjects)] in 21 subjects overall using Finn chambers on forearm skin. The reading was made at 2days and reactions were graded using the International Contact Dermatitis Research Group classification. RESULTS: Nickel levels on the fingers of platers, cashiers, sales assistants, caterers, and even office staff, were at or above the 0·035µgcm(-2) level at which 22% of nickel-allergic subjects will react (after applying a correction). The single open application of nickel study demonstrated a dose-response relationship, with no subjects reacting to ≤ 2·5µgcm(-2) , but increasing numbers reacting at the higher concentrations as follows: six of 21 (28%) at 5·0µgcm(-2) , six of 19 (31%) at 15µgcm(-2) , seven of 19 (37%) at 30µgcm(-2) and 11 of 18 (61%) at 45µgcm(-2) . CONCLUSIONS: This study confirms that nickel levels on the skin in coin handling occupations and some others are sufficient to induce an allergic contact dermatitis in some nickel-allergic subjects. A single application of 5µgcm(-2) when read at 2days induced a dermatitis reaction in six of 21 nickel-allergic subjects.

Cytochrome P450 testing for prescribing antipsychotics in adults with schizophrenia: systematic review and meta-analyses.

There is wide variability in the response of individuals to standard doses of antipsychotic drugs. It has been suggested that this may be partly explained by differences in the cytochrome P450 (CYP450) enzyme system responsible for metabolizing the drugs. We conducted a systematic review and meta-analyses to consider whether testing for CYP450 single nucleotide polymorphisms in adults starting antipsychotic treatment for schizophrenia predicts and leads to improvements in clinical outcomes. High analytic validity in terms of sensitivity and specificity was seen in studies reporting P450 testing. However, there was limited evidence of the role of CYP2D6 polymorphisms in antipsychotic efficacy, although there was an association between CYP2D6 genotype and extrapyramidal adverse effects. No studies reported on the prospective use of CYP2D6 genotyping tests in clinical practice. In conclusion, evidence of clinical validity and utility of CYP2D6 testing in patients being prescribed antipsychotics is lacking, and thus, routine pharmacogenetic testing prior to antipsychotic prescription cannot be supported at present. Further research is required to improve the evidence base and to generate data on clinical validity and clinical utility.

Pemetrexed for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of pemetrexed for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), in accordance with the licensed indication, based upon the evidence submission from the manufacturer (Eli Lilly) to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The primary clinical outcome measure was progression free survival (PFS). Secondary outcomes included overall survival (OS), time to worsening of symptoms, objective tumour response rate, adverse events and changes in lung cancer symptom scale. Data for two populations were presented: patients with non-squamous NSCLC histology and patients with adenocarcinoma histology. The clinical evidence was derived from a double-blind, placebo-controlled randomised controlled trial (RCT), the JMEN trial. The trial compared the use of pemetrexed + best supportive care (BSC ) as maintenance therapy, with placebo + BSC in patients with NSCLC (n = 663) who had received four cycles of platinum-based chemotherapy (CTX) and whose disease had not progressed. In the licensed population (patients with non-squamous histology), the trial demonstrated greater median PFS for patients treated with pemetrexed than for patients in the placebo arm [4.5 vs 2.6 months; hazard ratio (HR) 0.44; 95% confidence interval (CI) 0.36 to 0.55, p < 0.00001]. Median OS was also greater for the pemetrexed- treated patients (15.5 vs 10.3 months; HR 0.70; 95% CI 0.56 to 0.88, p = 0.002). In addition, tumour response and disease control rates were statistically significantly greater for patients who received pemetrexed. Patient survival rates at 1 year and 2 years were higher in the pemetrexed arm. The incremental cost-effectiveness ratios (ICERs) estimated by the manufacturer's model were 33,732 pounds per quality adjusted life-year (QALY) for the licensed nonsquamous population, and 39,364 pounds per QALY for the adenocarcinoma subgroup. Both of these ICERs were above the standard NICE willingness-to-pay range (20,000 pounds-30,000 pounds per QALY). The manufacturer also presented a case for pemetrexed to be considered as an end of life treatment. The ERG identified a number of problems in the economic model presented by the manufacturer; after correction, the base case ICER was re-estimated as 51,192 pounds per QALY gained and likely to exceed NICE's willingness-to-pay thresholds. Following a revised economic analysis submitted by the manufacturer, the AC accepted that an ICER of 47,000 pounds per QALY gained was most plausible. The AC also considered that maintenance treatment with pemetrexed fulfilled the end of life criteria.The guidance issued by NICE, on 20 June 20 2010, in TA190 as a result of the STA states that: People who have received pemetrexed in combination with cisplatin as first-line chemotherapy cannot receive pemetrexed maintenance treatment. 1.1 Pemetrexed is recommended as an option for the maintenance treatment of people with locally advanced or metastatic non-small-cell lung cancer other than predominantly squamous cell histology if disease has not progressed immediately following platinum-based chemotherapy in combination with gemcitabine, paclitaxel or docetaxel.