Lead exposure by E-waste disposal and recycling in Agbogbloshie, Ghana.

BACKGROUND: Agbogbloshie in Ghana is the world's biggest dumpsite for the informal recycling of electronic waste (e-waste). E-waste is dismantled by rudimentary methods without personal or environmental protection. Workers and occupants are exposed to lead. There are no data so far about the extent and the consequences. We therefore analyzed blood lead levels (BLL) and creatinine levels (CL). METHODS: Full blood samples and basic data (i.e. age, job, length of stay) were collected from dumpsite volunteers. BLL were measured by atomic absorption spectrometry; CL were assessed using the standard clinical laboratory procedures of Aachen Technical University. European BLL reference values were used as Ghana lacks its own. Statistical analysis was by non-parametric tests (Mann-Whitney U test), with p < 0.05. RESULTS: Participants of both sexes (n = 327; 12-68 years; median age 23 years) were assessed. Most workers were aged <30 years. The collective's BLL was in pathological range for 77.7%; 14% had a BLL >10.0 µg/dl with symptoms consistent with high lead exposure including severe (6.5%) and intermediate (39%) renal disorder. BLL above 15.0 µg/dl were found in 5.9% of all workers which is the German threshold for those working with lead. Elevated CL in a pathological range were found in 254 participants. This is problematic as 75% of the lead entering the body is excreted via urine. CONCLUSION: Most of our volunteers had pathological BLL and CL. Preventive strategies are necessary to reduce health risks, particularly for vulnerable populations (i.e. children, pregnant women).

Phenotypic and genotypic analysis of benzimidazole resistance in reciprocal genetic crosses of Haemonchus contortus.

Haemonchus contortus is arguably one of the most economically important and ubiquitous parasites of livestock globally and commonly involved in cases of anthelmintic resistance. Here, we performed reciprocal genetic crosses using susceptible (MHco3(ISE)) and multiple anthelmintic resistant (MHco18(UGA2004)) H. contortus isolates. Resultant admixed populations were designated MHco3/18 or MHco18/3, where the lead isolate reflects the origin of the females. Three independent filial generations were generated for each cross, which were subjected to bioassays, molecular approaches and population genetic analyses to investigate the phenotypic and genotypic inheritance of benzimidazole (BZ) resistance at each stage. A panel of microsatellite markers confirmed the success of the genetic cross as markers from both parents were seen in the F1 crosses. Egg hatch tests revealed a stark difference between the two F1 crosses with ED50 estimates for MHco18/3 being 9 times greater than those for MHco3/18. Resistance factors based on ED50 estimates ranged from 6 to 57 fold in the filial progeny compared to MHco3(ISE) parents. Molecular analysis of the F167Y and F200Y SNP markers associated with BZ resistance were analysed by pyrosequencing and MiSeq deep amplicon sequencing, which showed that MHco3/18.F1 and MHco18/3.F1 both had similar frequencies of the F200Y resistant allele (45.3% and 44.3%, respectively), whereas for F167Y, MHco18/3.F1 had a two-fold greater frequency of the resistant-allele compared to MHco3/18.F1 (18.2% and 8.8%, respectively). Comparison between pyrosequencing and MiSeq amplicon sequencing revealed that the allele frequencies derived from both methods were concordant at codon 200 (rc = 0.97), but were less comparable for codon 167 (rc = 0.55). The use of controlled reciprocal genetic crosses have revealed a potential difference in BZ resistance phenotype dependent on whether the resistant allele is paternally or maternally inherited. These findings provide new insight and prompt further investigation into the inheritance of BZ resistance in H. contortus.

Temporary threshold shift after noise exposure in hypobaric hypoxia at high altitude: results of the ADEMED expedition 2011.

OBJECTIVES: To evaluate whether there is an increased risk for noise-induced hearing loss at high altitude rsp. in hypobaric hypoxia. METHODS: Thirteen volunteers got standard audiometry at 125, 250, 500, 750, 1000, 1500, 2000, 3000, 4000, 6000, and 8000 Hz before and after 10 min of white noise at 90 dB. The system was calibrated for the respective altitude. Measurements were performed at Kathmandu (1400 m) and at Gorak Shep (5300 m) (Solo Khumbu/Nepal) after 10 days of acclimatization while on trek. Temporary threshold shift (TTS) was analyzed by descriptive statistics and by factor analysis. RESULTS: TTS is significantly more pronounced at high altitudes. Acclimatization does not provide any protection of the inner ear, although it increases arterial oxygen saturation. CONCLUSION: The thresholds beyond which noise protection is recommended (> 80 dB) or necessary (> 85 dB) are not sufficient at high altitudes. We suggest providing protective devices above an altitude of 1500 m ("ear threshold altitude") when noise level is higher than 75 dB and using them definitively above 80 dB. This takes the individual reaction on hypobaric hypoxia at high altitude into account.

Precision worm control in grazing lambs by targeting group treatment based on performance of sentinels.

Given the economic impact of gastrointestinal nematode infection on livestock farming worldwide, and increasing anthelmintic resistance, it is imperative to develop practical, efficient and sustainable control strategies. Targeted selective treatment (TST), whereby anthelmintic treatments are administered to animals individually, based on selection criteria such as weight gain, has been shown to successfully maintain animal productivity whilst reducing the selection pressure for anthelmintic resistance and the economic cost of treatment in experimental and commercial settings. Despite the benefits of the TST approach, the equipment and time required to monitor animals individually make this strategy unsuitable for some farming enterprises. The sentinel group approach aims to maintain the benefits observed using TST whilst reducing these requirements. The study involved two experiments, each following a group of 80 lambs through their first grazing season. Anthelmintic treatment of the whole group was determined by monitoring the weight gain of identified sentinel lambs within it every 2 weeks: when 40% of the sentinel lambs failed to reach their weight gain targets, the whole group was treated. The sentinel lambs consisted of 45% of the group (n = 36) in experiment one and 20% (n = 16) in experiment two. A control group of 20 lambs was co-grazed with the main group during both experiments; in experiment one, the sentinel approach was compared with a TST approach, in which control lambs were treated on an individual basis in response to weight gain. In experiment two, the sentinel approach was compared with conventional prophylaxis, where all lambs in the control group were treated at strategic time points throughout the season (= strategic prophylactic treatment). The sentinel lambs were found to be representative of overall group performance regardless of the proportion of sentinels within the group: they recorded similar growth rates and reached weight gain targets simultaneously at each time point and overall. Live-weight gain was also similar between sentinel and control animals in both experiments. The findings of the current study suggest that monitoring sentinel lambs comprising 20% of a group of grazing lambs is sufficient to determine the need for anthelmintic treatment within the whole group, and that this approach maintains production in line with conventional or TST treatment regimes.

Human myelomeningocele risk and ultra-rare deleterious variants in genes associated with cilium, WNT-signaling, ECM, cytoskeleton and cell migration.

Myelomeningocele (MMC) affects one in 1000 newborns annually worldwide and each surviving child faces tremendous lifetime medical and caregiving burdens. Both genetic and environmental factors contribute to disease risk but the mechanism is unclear. This study examined 506 MMC subjects for ultra-rare deleterious variants (URDVs, absent in gnomAD v2.1.1 controls that have Combined Annotation Dependent Depletion score ≥ 20) in candidate genes either known to cause abnormal neural tube closure in animals or previously associated with human MMC in the current study cohort. Approximately 70% of the study subjects carried one to nine URDVs among 302 candidate genes. Half of the study subjects carried heterozygous URDVs in multiple genes involved in the structure and/or function of cilium, cytoskeleton, extracellular matrix, WNT signaling, and/or cell migration. Another 20% of the study subjects carried heterozygous URDVs in candidate genes associated with gene transcription regulation, folate metabolism, or glucose metabolism. Presence of URDVs in the candidate genes involving these biological function groups may elevate the risk of developing myelomeningocele in the study cohort.

Understanding young peoples' and family members' views of treatment for first episode psychosis in a randomised controlled trial (MAPS).

BACKGROUND: There is limited evidence to inform treatment decision-making in adolescents experiencing first episode psychosis (FEP). In the MAPS trial (Managing Adolescent first Episode Psychosis: a feasibility Study), adolescents with FEP received either antipsychotic medication (AP), psychological intervention (PI), or both. We investigated treatment views of young people and family members across each treatment arm of MAPS. METHODS: Thirteen adolescents participating in MAPS and eighteen family members attended in-depth audio-recorded interviews to discuss trial treatments. Interviews were analysed using inductive Thematic Analysis, identifying salient themes across these accounts. FINDINGS: Family members in particular reported an urgent need for treatment regardless of type. Both AP and PI were broadly viewed as acceptable treatment approaches, but for differing reasons which participants weighed against a range of concerns. AP were often seen to reduce symptoms of psychosis, though participants expressed concerns about side effects. PI were viewed as interactive treatment approaches that helped improve understanding of psychosis and enhanced coping, although some found PI emotionally and cognitively challenging. Combining treatments was seen to maximise benefits, with a perceived interaction whereby AP facilitated engagement with PI. INTERPRETATION: Acceptability of and engagement with treatments for FEP may differ between individual young people and their family/carers. In order to be able to offer fully informed choices, and determine an optimum treatment approach for young people with FEP, definitive trial evidence should be established to determine wanted and unwanted treatment impacts. FUNDING: NIHR HTA programme (project number 15/31/04).

Emergent Premedication for Contrast Allergy Prior to Endovascular Treatment of Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Management of contrast media allergies may lead to treatment delays in patients with acute ischemic stroke undergoing endovascular therapy. The optimal premedication strategy remains unclear. The aim of this report was to analyze our experience with emergent administration of premedication regimens before endovascular therapy. MATERIALS AND METHODS: We retrospectively reviewed prospective data for all patients undergoing endovascular therapy from 2012 to 2019 at an academic comprehensive stroke center. Records of patients with documented contrast allergy were reviewed and analyzed. Data collected included stroke risk factors and characteristics, historical contrast reaction details, premedication regimens administered, and signs or symptoms of allergic reaction developing post-endovascular therapy. Hospital arrival time to endovascular therapy was compared with that in those who did not have a history of contrast allergy. RESULTS: We analyzed 1521 patients undergoing endovascular therapy; 60 (4%) had documented contrast allergies and constituted the study cohort. The median age was 73 years (interquartile range, 66-81 years), and 65% were women. The median time from premedication to contrast was 24 minutes (interquartile range, 0-36 minutes). Forty-three patients (72%) proceeded directly to endovascular therapy; in 17 patients, the first contrast exposure was CTA. Time from hospital arrival to endovascular therapy was not slower for patients with documented allergies (96 versus 134 minutes, P = .32). No patients experienced a contrast media reaction. CONCLUSIONS: In a single-institution cohort study of 60 consecutive patients with documented contrast allergies undergoing endovascular therapy with emergent premedication en route to (or in) the neuroangiography suite, no patients experienced allergic symptoms. This pragmatic approach may be safe for patients who have documented contrast media allergies.

Warm Circumpolar Deep Water transport toward Antarctica driven by local dense water export in canyons.

Poleward transport of warm Circumpolar Deep Water (CDW) has been linked to melting of Antarctic ice shelves. However, even the steady-state spatial distribution and mechanisms of CDW transport remain poorly understood. Using a global, eddying ocean model, we explore the relationship between the cross-slope transports of CDW and descending Dense Shelf Water (DSW). We find large spatial variability in CDW heat and volume transport around Antarctica, with substantially enhanced flow where DSW descends in canyons. The CDW and DSW transports are highly spatially correlated within ~20 km and temporally correlated on subdaily time scales. Focusing on the Ross Sea, we show that the relationship is driven by pulses of overflowing DSW lowering sea surface height, leading to net onshore CDW transport. The majority of simulated onshore CDW transport is concentrated in cold-water regions, rather than warm-water regions, with potential implications for ice-ocean interactions and global sea level rise.

The Microalbuminuria Education Medication and Optimisation (MEMO) study: 4 years follow-up of multifactorial intervention in high-risk individuals with type 2 diabetes.

AIMS: The Microalbuminuria Education Medication and Optimisation (MEMO) study, revealed improved cardiovascular risk and glycaemic control with 18 months of intensive multifactorial intervention in high-risk people with type 2 diabetes, without any increase in severe hypoglycaemia. Our aim was to assess longer-term outcomes at 4-year follow-up in these participants. METHODS: Some 189 individuals with type 2 diabetes and microalbuminuria were recruited from a multi-ethnic population in Leicestershire, UK. The intervention group (n = 95) received multifactorial intervention with self-management education, and the control group (n = 94) received usual care. The primary outcome was change in HbA1c , and secondary outcomes were blood pressure (BP), cholesterol, microalbuminuria, estimated GFR, cardiovascular risk scores and major adverse cardiovascular events. RESULTS: Some 130 participants (68.7%), mean (sd) age 60.8 (10.4) years, duration of diabetes 11.5 (9.7) years, completed 4 years of follow-up. Mean change [95% confidence intervals (CI)] in HbA1c over 4 years was greater with intensive intervention compared with control (-3 mmol/mol, 95% CI -4.95,-1.11; -0.4%, 95% CI -0.67,-0.15; P = 0.002). Significant improvements over the 4 years were also seen in systolic BP (-7.3 mmHg, 95% CI -11.1, -3.5; P < 0.001), diastolic BP (-2.9 mmHg, 95% CI -5.4, -0.3; P = 0.026), cholesterol (-0.3 mmol/l, 95% CI -0.52,-0.12; P = 0.002), and 10-year coronary heart disease (-5.3, 95% CI -8.2,-2.3; P < 0.001) and stroke risk (-4.4, 95% CI -7.5, -1.3; P < 0.001). CONCLUSION: Multifactorial intervention with structured diabetes self-management education compared with usual diabetes care has benefits for cardio-metabolic risk factor profile. There was no increase in severe hypoglycaemia and cardiovascular mortality despite intensive glycaemic control, although the study was not powered to assess these outcomes.

Genomic Epidemiology as a Public Health Tool to Combat Mosquito-Borne Virus Outbreaks.

Next-generation sequencing technologies, exponential increases in the availability of virus genomic data, and ongoing advances in phylogenomic methods have made genomic epidemiology an increasingly powerful tool for public health response to a range of mosquito-borne virus outbreaks. In this review, we offer a brief primer on the scope and methods of phylogenomic analyses that can answer key epidemiological questions during mosquito-borne virus public health emergencies. We then focus on case examples of outbreaks, including those caused by dengue, Zika, yellow fever, West Nile, and chikungunya viruses, to demonstrate the utility of genomic epidemiology to support the prevention and control of mosquito-borne virus threats. We extend these case studies with operational perspectives on how to best incorporate genomic epidemiology into structured surveillance and response programs for mosquito-borne virus control. Many tools for genomic epidemiology already exist, but so do technical and nontechnical challenges to advancing their use. Frameworks to support the rapid sharing of multidimensional data and increased cross-sector partnerships, networks, and collaborations can support advancement on all scales, from research and development to implementation by public health agencies.

Similarities and differences in the biotransformation and transcriptomic responses of Caenorhabditis elegans and Haemonchus contortus to five different benzimidazole drugs.

We have undertaken a detailed analysis of the biotransformation of five of the most therapeutically important benzimidazole anthelmintics - albendazole (ABZ), mebendazole (MBZ), thiabendazole (TBZ), oxfendazole (OxBZ) and fenbendazole (FBZ) - in Caenorhabditis elegans and the ruminant parasite Haemonchus contortus. Drug metabolites were detected by LC-MS/MS analysis in supernatants of C. elegans cultures with a hexose conjugate, most likely glucose, dominating for all five drugs. This work adds to a growing body of evidence that glucose conjugation is a major pathway of xenobiotic metabolism in nematodes and may be a target for enhancement of anthelmintic potency. Consistent with this, we found that biotransformation of albendazole by C. elegans reduced drug potency. Glucose metabolite production by C. elegans was reduced in the presence of the pharmacological inhibitor chrysin suggesting that UDP-glucuronosyl/glucosyl transferase (UGT) enzymes may catalyze benzimidazole glucosidation. Similar glucoside metabolites were detected following ex vivo culture of adult Haemonchus contortus. As a step towards identifying nematode enzymes potentially responsible for benzimidazole biotransformation, we characterised the transcriptomic response to each of the benzimidazole drugs using the C. elegans resistant strain CB3474 ben-1(e1880)III. In the case of albendazole, mebendazole, thiabendazole, and oxfendazole the shared transcriptomic response was dominated by the up-regulation of classical xenobiotic response genes including a shared group of UGT enzymes (ugt-14/25/33/34/37/41/8/9). In the case of fenbendazole, a much greater number of genes were up-regulated, as well as developmental and brood size effects suggesting the presence of secondary drug targets in addition to BEN-1. The transcriptional xenobiotic response of a multiply resistant H. contortus strain UGA/2004 was essentially undetectable in the adult stage but present in the L3 infective stage, albeit more muted than C. elegans. This suggests that xenobiotic responses may be less efficient in stages of parasitic nematodes that reside in the host compared with the free-living stages.

Joint range of motion entropy changes in response to load carriage in military personnel.

BACKGROUND: Overuse accounts for 82% of injuries in military personnel, and these occur predominantly in the spine and lower limbs. While non-linear analyses have shown changes in overall stability of the movement during load carriage, individual joint contributions have not been studied. The concept of entropy compensation between task, organism and environmental constraints is studied at a joint level. RESEARCH QUESTION: The aim of this study was to investigate whether using different methods of loading by military personnel would have an effect on the sample entropy of the joint ranges of motion. METHODS: Eleven male reserve infantry army soldiers (age: 22 ±â€¯2 years; height: 1.80 ±â€¯0.06 m; mass: 89.3 ±â€¯14.4 kg) walked an outdoor, 800 m course under 5 load conditions: unloaded, 15 kg backpack, 25 kg backpack, 15 kg webbing and backpack and 25 kg webbing and backpack. Kinematic data was recorded at 240 Hz using the Xsens motion capture system. The ranges of motion (ROM) of the spine, hips and knee were calculated for each gait cycle. Mean ROM, coefficient of variation (CV) of the ROM and the sample entropy of the ROM were compared between conditions. RESULTS: Spine side flexion ROM decreased significantly from the control condition in all loaded conditions, while sample entropy of the spine side flexion ROM increased in some conditions with no significant change in CV. Conversely, the hip flexion ROM increased significantly from the control, while sample entropy of the hip flexion ROM decreased. SIGNIFICANCE: These results suggest that entropy compensation may propagate at a joint level. Understanding that a decrease in certainty with which a joint angle is selected, may be accompanied by an increase at a neighbouring joint. This could be significant in monitoring injuries as a result of environmental or task constraints.

Zika transmission patterns: a meta-review.

OBJECTIVE: To assesses what is known and identify knowledge gaps for Zika virus (ZIKV) transmission patterns. METHODS: Meta-review searching the databases BioSys; Cochrane Infectious Diseases Group Specialised Register and Cochrane Central Register of Controlled Trials; EMBASE; Google Scholar; LILACS; MEDLINE (PubMed); Web of Science; and WHOLIS with the term 'ZIKA'. Systematic reviews and reviews specifying the search methods and describing potential modes of transmission were eligible for analysis. RESULTS: Of 5,401 hits for 'Zika', 44 studies were assessed and 11 included after applying in- and exclusion criteria: six systematic reviews and five reviews with specified methods, covering all ways of possible transmission. Results can be grouped into transmission routes with good evidence and agreement between the studies (evidence on vector, mother-to-child and sexual transmission) and transmission routes with limited evidence. Transmission by breastfeeding, intrapartum, by animal bites or laboratory-based remains inconclusive, as these routes are suggested by single studies only. The risk of transfusion transmission is described and public health measures for safe transfusion should be taken as available. CONCLUSION: Our results imply the need for public health measures to limit transmission via vectors, mother-to-child, sexual transmission and blood transfusion. Also needed are long-term prospective cohort studies covering periods of active Zika virus transmission and measuring epidemiological parameters to establish evidence on other routes of transmission; seroprevalence studies; transmission dynamics modelling and modelling health impacts by different modes of transmission.

OBJECTIF: Evaluer ce que l'on sait et identifier les lacunes dans les connaissances sur les profils de transmission du virus Zika (ZIKV). MÉTHODES: Méta-analyse de recherche dans les bases de données BioSys, Cochrane Infectious Diseases Specialised Register et le Registre Central Cochrane des Essais Contrôlés, EMBASE, Google Scholar, LILACS MEDLINE (PubMed), Web de la Science et WHOLIS avec le terme «Zika¼. Les revues systématiques et les revues spécifiant les méthodes de recherche et décrivant les modes de transmission potentiels étaient éligibles pour l'analyse. RÉSULTATS: Sur 5.401 résultats correspondant à «Zika¼, 44 études ont été évaluées et 11 incluses après application des critères d'inclusion et d'exclusion: 6 revues systématiques et 5 revues avec des méthodes spécifiées, couvrant tous les modes de transmission possibles. Les résultats peuvent être regroupés en voies de transmission avec des preuves solides et une concordance entre les études (preuves sur la transmission vectorielle, transmission mère-enfant et sexuelle) et les voies de transmission avec des preuves limitées. La transmission par l'allaitement, par voie intra-partum, par des morsures d'animaux ou via le laboratoire reste non conclusive, car ces voies ne sont suggérées que par des études uniques. Le risque de transmission par transfusion est décrit et des mesures de santé publique visant à garantir une transfusion sans danger doivent être prises dès que possible. CONCLUSION: Nos résultats insinuent la nécessité de prendre des mesures de santé publique pour limiter la transmission par le biais des vecteurs, la transmission mère-enfant, la transmission sexuelle et la transfusion sanguine. Des études de cohorte prospectives à long terme portant sur des périodes de transmission active du virus Zika et des mesures de paramètres épidémiologiques sont également nécessaires pour établir des preuves d'autres voies de transmission; des études de séroprévalence; la modélisation de la dynamique de transmission et la modélisation des impacts sur la santé par différents modes de transmission.

Sleep duration and psychotic experiences in patients at risk of psychosis: A secondary analysis of the EDIE-2 trial.

Sleep disturbance is common among individuals at risk of psychosis, yet few studies have investigated the relationship between sleep disturbance and clinical trajectory. The Early Detection and Intervention Evaluation (EDIE-2) trial provides longitudinal data on sleep duration and individual psychotic experiences from a cohort of individuals at risk of psychosis, which this study utilises in an opportunistic secondary analysis. Shorter and more variable sleep was hypothesised to be associated with more severe psychotic experiences and lower psychological wellbeing. Mixed effect models were used to test sleep duration and range as predictors of individual psychotic experiences and psychological wellbeing over the 12-24 months (with assessments every 3 months) in 160 participants. Shorter sleep duration was associated with more severe delusional ideas and hallucinations cross-sectionally and longitudinally. The longitudinal relationships did not remain significant after conservative controls were added for the previous severity of psychotic experiences. No significant relationships were found between the sleep variables and other psychotic experiences (e.g. cognitive disorganisation), or psychological wellbeing. The results support a relationship between shorter sleep duration and delusional ideas and hallucinations. Future studies should focus on improving sleep disturbance measurement, and test whether treating sleep improves clinical trajectory in the at-risk group.

Improving quality and safety in paediatric spinal surgery: the team approach.

Aims: The aim of this study was to evaluate improvements in the quality and safety of paediatric spinal surgery following the implementation of a specialist Paediatric Spinal Surgical Team (PSST) in the operating theatre. Patients and Methods: A retrospective consecutive case study of paediatric spinal operations before (between January 2008 and December 2009), and after (between January 2012 and December 2013) the implementation of PSST, was performed. A comparative analysis of outcome variables including surgical site infection (SSI), operating time (ORT), blood loss (BL), length of stay (LOS), unplanned staged procedures (USP) and transfusion rates (allogenic and cell-saver) was performed between the two groups. The rate of complications during the first two postoperative years was also compared between the groups. Results: There were 130 patients in the pre-PSST group and 277 in the post-PSST group. The age, gender, body mass index (BMI), preoperative Cobb angle of the major curve and the number of levels involved were similar between the groups. There were statistically significant differences in SSI, ORT, LOS, allogenic blood transfusion volume (ABTV), and USPs between the groups. There was a 94% decrease in the rate of SSI's in the post-PSST group. Patients in the post-PSST group had a mean reduction in ORT of 53 minutes (sd 7.7) (p = 0.013), LOS by 5.4 days (sd 1.8) (p = 0.019), and ABTV by 226.3 ml (sd 28.4) (p < 0.001). There were significantly more USPs in the pre-PSST group (6.2%) compared with the post-PSST group (2.9%) (p = 0.001). Multivariate regression showed that the effect of PSST remained significant for ORT, LOS, BL, ABVT and cell-saver amount transfused (p = 0.0001). The odds of having a SSI were tenfold higher and the odds of receiving a blood transfusion were 2.4 times higher, respectively, in the pre-PSST group (p = 0.004 and p = 0.011). The rate of complications within the first two postoperative years was significantly higher in the pre-PSST group (13.1%) compared with the post-PSST group (4.3%) (p < 0.001). Conclusion: The implementation of a PSST in the operating theatre significantly improves the outcomes in paediatric spinal surgery. Cite this article: Bone Joint J 2018;100-B:493-8.

A (five-)level playing field for mental health conditions?: exploratory analysis of EQ-5D-5L-derived utility values.

PURPOSE: Economic evaluations of mental health interventions often measure health benefit in terms of utility values derived from the EQ-5D. For the five-level version of the EQ-5D, there are two methods of estimating utility [crosswalk and stated preference (5L-SP)]. This paper explores potential impacts for researchers and decision-makers when comparing utility values derived from either method in the specific context of mental health. METHODS: Baseline EQ-5D-5L data from three large randomised controlled trials of interventions for mental health conditions were analysed. Utility values were generated using each method. Mean utility values were compared using a series of t tests on pooled data and subgroups. Scenario analyses explored potential impacts on cost-effectiveness decisions. RESULTS: EQ-5D data were available for 1399 participants. The mean utility value for each trial was approximately 0.08 higher when estimated using the 5L-SP approach compared to crosswalk (p < 0.0001). The difference was greatest among people reporting extreme anxiety/depression (mean utility 5L-SP 0.309, crosswalk 0.084; difference = 0.225; p < 0.0001). Identical improvements in health status were associated with higher costs to gain one QALY with the 5L-SP approach; this is more pronounced when improvements are across all domains compared to improvements on the anxiety/depression domain only. CONCLUSIONS: The two approaches produce significantly different utility values in people with mental health conditions. Resulting differences in cost per QALY estimates suggest that thresholds of cost-effectiveness may also need to be reviewed. Researchers and decision-makers should exercise caution when comparing or synthesising data from trials of mental health interventions using different utility estimation approaches.

Cardiopulmonary interactions with beta-blockers and inhaled therapy in COPD.

BACKGROUND: Beta-blockers remain underused in patients with chronic obstructive pulmonary disease (COPD) and cardiovascular disease. AIM: We compared how different inhaled therapies affect tolerability of bisoprolol and carvedilol in moderate to severe COPD. DESIGN: A randomized, open label, cross-over study. METHODS: We compared the cardiopulmonary interactions of bisoprolol 5 mg qd or carvedilol 12.5 mg bid for 6 weeks in conjunction with: (i) triple: inhaled corticosteroid/long acting beta-agonist/long acting muscarinic antagonist (ICS + LABA + LAMA), (ii) dual: ICS + LABA and (iii) ICS alone. RESULTS: Eighteen patients completed, all ex-smokers, mean age 65 years, forced expiratory volume in 1 s (FEV1) 52% predicted. Bisoprolol and carvedilol produced comparable significant reduction in resting and exercise heart rate. FEV1, forced vital capacity and lung compliance (AX) were significantly lower with carvedilol vs. bisoprolol while taking concomitant ICS/LABA (P < 0.05) but not ICS/LABA/LAMA. CONCLUSIONS: In summary, bisoprolol was better tolerated than carvedilol on pulmonary function at doses which produced equivalent cardiac beta-1 blockade. Worsening of pulmonary function with carvedilol was mitigated by concomitant inhaled LAMA (tiotropium) with LABA (formoterol), but not LABA alone. Registered at clinicaltrials.gov: NCT01656005.

Research awareness, attitudes and barriers among clinical staff in a regional cancer centre. Part 1: a quantitative analysis.

Research is of key importance in delivering high-quality patient care through evidence-based practice. Attitude towards research and barriers to research can have an impact on research activity. A survey was conducted to establish the levels of research awareness and attitudes among clinical staff groups in this regional cancer centre and identify any barriers to participation in research. The survey consisted of 26 questions and was distributed electronically and completed online. The response rate was 22.3% (n = 123). All participants felt that clinical research will help the regional cancer centre develop and progress treatments in the future. A positive attitude towards research was evident and consistent across professional groups. The main identified barriers to research included lacking the required knowledge, skills and training, lacking support from managers, and lack of opportunity or time to be involved in research, in particular for allied health professionals. However, there appears to be the foundation of a healthy research culture for nurses supported by management. The results of the survey support the implementation of an action plan based on the recommendations of this journal article.

Implications of between-isolate variation for climate change impact modelling of Haemonchus contortus populations.

The impact of climate change on parasites and parasitic diseases is a growing concern and numerous empirical and mechanistic models have been developed to predict climate-driven spatial and temporal changes in the distribution of parasites and disease risk. Variation in parasite phenotype and life-history traits between isolates could undermine the application of such models at broad spatial scales. Seasonal variation in the transmission of the haematophagous gastrointestinal nematode Haemonchus contortus, one of the most pathogenic helminth species infecting sheep and goats worldwide, is primarily determined by the impact of environmental conditions on the free-living stages. To evaluate variability in the development success and mortality of the free-living stages of H. contortus and the impact of this variability on future climate impact modelling, three isolates of diverse origin were cultured at a range of temperatures between 15°C and 37°C to determine their development success compared with simulations using the GLOWORM-FL H. contortus model. No significant difference was observed in the developmental success of the three isolates of H. contortus tested, nor between isolates and model simulations. However, development success of all isolates at 37°C was lower than predicted by the model, suggesting the potential for overestimation of transmission risk at higher temperatures, such as those predicted under some scenarios of climate change. Recommendations are made for future climate impact modelling of gastrointestinal nematodes.

Health-related quality of life after treatment for neoplasia of the major salivary glands: a pilot study.

Treatment of malignancy of the salivary glands risks damage to the cranial nerves, and clinicians' traditional view has been that this will result in adverse effects on physical function and subsequent health-related quality of life (QoL). Preservation of nerves has been advocated to lessen this impact, but we know of no evidence that sacrifice of the facial nerve has any effect on subsequent QoL. We collected data prospectively before and after operation for all malignancies of the major salivary glands treated over five years using two health-related QoL questionnaires: the University of Washington Quality of Life Questionnaire and the Patient Concerns Inventory. Fifteen of17 eligible patients fulfilled the inclusion criteria by having assessments completed both before and after operation. Scores for QoL after treatment of cancer of the submandibular gland dropped at six months, but had resolved to more than 80% of the pretreatment score by a year, with the exception of the domains taste and saliva. The four patients who had weakness of the facial nerve after treatment had appreciable reductions in the physical function components of the QoL domains, but no significant reduction in the social-emotional domains. Use of the Patient Concerns Inventory enables tailoring of services towards those clinicians who a patient feels are potentially most likely to help alleviate factors that have an adverse effect on QoL. Sacrifice of the facial nerve in malignant parotid gland disease results in a considerable reduction in functional health-related QoL scores. Methods to ensure clearance of the tumour while limiting the effects on facial nerve function should always be considered.