New insights into sequence variation in the IGS region of 21 cyathostomin species and the implication for molecular identification

Cyathostomins comprise a group of 50 species of parasitic nematodes that infect equids. Ribosomal DNA sequences, in particular the intergenic spacer (IGS) region, have been utilized via several methodologies to identify pre-parasitic stages of the commonest species that affect horses. These methods rely on the availability of accurate sequence information for each species, as well as detailed knowledge of the levels of intra- and inter-specific variation. Here, the IGS DNA region was amplified and sequenced from 10 cyathostomin species for which sequence was not previously available. Also, additional IGS DNA sequences were generated from individual worms of 8 species already studied. Comparative analysis of these sequences revealed a greater range of intra-specific variation than previously reported (up to 23%); whilst the level of inter-specific variation (3-62%) was similar to that identified in earlier studies. The reverse line blot (RLB) method has been used to exploit the cyathostomin IGS DNA region for species identification. Here, we report validation of novel and existing DNA probes for identification of cyathostomins using this method and highlight their application in differentiating life-cycle stages such as third-stage larvae that cannot be identified to species by morphological means.

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations.

METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls.

RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)).

CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.

Analysis of single nucleotide polymorphisms implicate mTOR signalling in the development of new-onset diabetes after transplantation

Introduction
Despite excellent first year outcomes in kidney transplantation, there remain significant long-term complications related to new-onset diabetes after transplantation (NODAT). The purpose of this study was to validate the findings of previous investigations of candidate gene variants in patients undergoing a protocolised, contemporary immunosuppression regimen, using detailed serial biochemical testing to identify NODAT development.

Methods
One hundred twelve live and deceased donor renal transplant recipients were prospectively followed-up for NODAT onset, biochemical testing at days 7, 90, and 365 after transplantation. Sixty-eight patients were included after exclusion for non-white ethnicity and pre-transplant diabetes. Literature review to identify candidate gene variants was undertaken as described previously.

Results
Over 25% of patients developed NODAT. In an adjusted model for age, sex, BMI, and BMI change over 12 months, five out of the studied 37 single nucleotide polymorphisms (SNPs) were significantly associated with NODAT: rs16936667:PRDM14 OR 10.57;95% CI 1.8–63.0;p = 0.01, rs1801282:PPARG OR 8.5; 95% CI 1.4–52.7; p = 0.02, rs8192678:PPARGC1A OR 0.26; 95% CI 0.08–0.91; p = 0.03, rs2144908:HNF4A OR 7.0; 95% CI 1.1–45.0;p = 0.04 and rs2340721:ATF6 OR 0.21; 95%CI 0.04–1.0; p = 0.05.

Conclusion
This study represents a replication study of candidate SNPs associated with developing NODAT and implicates mTOR as the central regulator via altered insulin sensitivity, pancreatic β cell, and mitochondrial survival and dysfunction as evidenced by the five SNPs.

General significance
1) Highlights the importance of careful biochemical phenotyping with oral glucose tolerance tests to diagnose NODAT in reducing time to diagnosis and missed cases.
2)This alters potential genotype:phenotype association.
3)The replication study generates the hypothesis that mTOR signalling pathway may be involved in NODAT development.

Ataluren for the treatment of nonsense-mutation cystic fibrosis: a randomised, double-blind, placebo-controlled phase 3 trial

Background: Ataluren was developed to restore functional protein production in genetic disorders caused by nonsense mutations, which are the cause of cystic fibrosis in 10% of patients. This trial was designed to assess the efficacy and safety of ataluren in patients with nonsense-mutation cystic fibrosis. 

Methods: This randomised, double-blind, placebo-controlled, phase 3 study enrolled patients from 36 sites in 11 countries in North America and Europe. Eligible patients with nonsense-mutation cystic fibrosis (aged ≥6 years; abnormal nasal potential difference; sweat chloride >40 mmol/L; forced expiratory volume in 1 s [FEV₁] ≥40% and ≤90%) were randomly assigned by interactive response technology to receive oral ataluren (10 mg/kg in morning, 10 mg/kg midday, and 20 mg/kg in evening) or matching placebo for 48 weeks. Randomisation used a block size of four, stratified by age, chronic inhaled antibiotic use, and percent-predicted FEV₁. The primary endpoint was relative change in percent-predicted FEV₁ from baseline to week 48, analysed in all patients with a post-baseline spirometry measurement. This study is registered with ClinicalTrials.gov, number NCT00803205. 

Findings: Between Sept 8, 2009, and Nov 30, 2010, 238 patients were randomly assigned, of whom 116 in each treatment group had a valid post-baseline spirometry measurement. Relative change from baseline in percent-predicted FEV₁ did not differ significantly between ataluren and placebo at week 48 (-2·5% vs -5·5%; difference 3·0% [95% CI -0·8 to 6·3]; p=0·12). The number of pulmonary exacerbations did not differ significantly between treatment groups (rate ratio 0·77 [95% CI 0·57-1·05]; p=0·0992). However, post-hoc analysis of the subgroup of patients not using chronic inhaled tobramycin showed a 5·7% difference (95% CI 1·5-10·1) in relative change from baseline in percent-predicted FEV₁ between the ataluren and placebo groups at week 48 (-0·7% [-4·0 to 2·1] vs -6·4% [-9·8 to -3·7]; nominal p=0·0082), and fewer pulmonary exacerbations in the ataluern group (1·42 events [0·9-1·9] vs 2·18 events [1·6-2·7]; rate ratio 0·60 [0·42-0·86]; nominal p=0·0061). Safety profiles were generally similar for ataluren and placebo, except for the occurrence of increased creatinine concentrations (ie, acute kidney injury), which occurred in 18 (15%) of 118 patients in the ataluren group compared with one (<1%) of 120 patients in the placebo group. No life-threatening adverse events or deaths were reported in either group. I

nterpretation: Although ataluren did not improve lung function in the overall population of nonsense-mutation cystic fibrosis patients who received this treatment, it might be beneficial for patients not taking chronic inhaled tobramycin. 

Funding: PTC Therapeutics, Cystic Fibrosis Foundation, US Food and Drug Administration's Office of Orphan Products Development, and the National Institutes of Health. 

Assessment of clinical response to ivacaftor with lung clearance index in cystic fibrosis patients with a G551D-CFTR mutation and preserved spirometry:A randomised controlled trial

Background: Ivacaftor has shown a clinical benefit in patients with cystic fibrosis who have the G551D-CFTR mutation and reduced lung function. Lung clearance index (LCI) using multiple-breath washout might be an alternative to and more sensitive method than forced expiratory volume in 1 s (FEV₁) to assess treatment response in the growing number of children and young adults with cystic fibrosis who have normal spirometry. The aim of the study was to assess the treatment effects of ivacaftor on LCI in patients with cystic fibrosis, a G551D-CFTR mutation, and an FEV₁ >90% predicted. Methods: This phase 2, multicentre, placebo-controlled, double-blind 2×2 crossover study of ivacaftor treatment was conducted in patients with cystic fibrosis, at least one G551D-CFTR allele, and an FEV₁ >90% predicted. Patients also had to have an LCI higher than 7·4 at screening, age of 6 years or older, and a weight higher than or equal to 15 kg. Eligible patients were randomly allocated to receive one of two treatment sequences (placebo first followed by ivacaftor 150 mg twice daily [sequence 1] or ivacaftor 150 mg twice daily first followed by placebo [sequence 2]) of 28 days' treatment in each period, with a 28-day washout between the two treatment periods. Randomisation (ratio 1:1) was done with block sizes of 4, and all site personnel including the investigator, the study monitor, and the Vertex study team were masked to treatment assignment. The primary outcome measure was change from baseline in LCI. The study is registered at ClinicalTrials.gov, NCT01262352. Findings: Between February and November, 2011, 21 patients were enrolled, of which 11 were assigned to the sequence 1 group, and 10 to the sequence 2 group. 20 of these patients received treatment and 17 completed the trial (eight in sequence 1 group and 9 in sequence 2 group). Treatment with ivacaftor led to significant improvements compared with placebo in LCI (difference between groups in the average of mean changes from baseline at days 15 and 29 was -2·16 [95% CI -2·88 to -1·44]; p<0·0001). Adverse events experienced by study participants were similar between treatment groups; at least one adverse event was reported by 15 (79%) of 19 patients who received placebo and 13 (72%) of 18 patients who received ivacaftor. No deaths occurred during study period. Interpretation: In patients with cystic fibrosis aged 6 years or older who have at least one G551D-CFTR allele, ivacaftor led to improvements in LCI. LCI might be a more sensitive alternative to FEV₁ in detecting response to intervention in these patients with mild lung disease. Funding: Vertex Pharmaceuticals Incorporated. © 2013 Elsevier Ltd.

Fluid balance, intradialytic hypotension, and outcomes in critically ill patients undergoing renal replacement therapy: a cohort study

Introduction: In this cohort study, we explored the relationship between fluid balance, intradialytic hypotension and outcomes in critically ill patients with acute kidney injury (AKI) who received renal replacement therapy (RRT).

Methods: We analysed prospectively collected registry data on patients older than 16 years who received RRT for at least two days in an intensive care unit at two university-affiliated hospitals. We used multivariable logistic regression to determine the relationship between mean daily fluid balance and intradialytic hypotension, both over seven days following RRT initiation, and the outcomes of hospital mortality and RRT dependence in survivors.

Results: In total, 492 patients were included (299 male (60.8%), mean (standard deviation (SD)) age 62.9 (16.3) years); 251 (51.0%) died in hospital. Independent risk factors for mortality were mean daily fluid balance (odds ratio (OR) 1.36 per 1000 mL positive (95% confidence interval (CI) 1.18 to 1.57), intradialytic hypotension (OR 1.14 per 10% increase in days with intradialytic hypotension (95% CI 1.06 to 1.23)), age (OR 1.15 per five-year increase (95% CI 1.07 to 1.25)), maximum sequential organ failure assessment score on days 1 to 7 (OR 1.21 (95% CI 1.13 to 1.29)), and Charlson comorbidity index (OR 1.28 (95% CI 1.14 to 1.44)); higher baseline creatinine (OR 0.98 per 10 mu mol/L (95% CI 0.97 to 0.996)) was associated with lower risk of death. Of 241 hospital survivors, 61 (25.3%) were RRT dependent at discharge. The only independent risk factor for RRT dependence was pre-existing heart failure (OR 3.13 (95% CI 1.46 to 6.74)). Neither mean daily fluid balance nor intradialytic hypotension was associated with RRT dependence in survivors. Associations between these exposures and mortality were similar in sensitivity analyses accounting for immortal time bias and dichotomising mean daily fluid balance as positive or negative. In the subgroup of patients with data on pre-RRT fluid balance, fluid overload at RRT initiation did not modify the association of mean daily fluid balance with mortality.

Conclusions: In this cohort of patients with AKI requiring RRT, a more positive mean daily fluid balance and intradialytic hypotension were associated with hospital mortality but not with RRT dependence at hospital discharge in survivors.

Early-type stars observed in the ESO UVES Paranal observatory project - IV. studies of CN, CH+ and CH in the interstellar medium

High spectral resolution (~80 000) and signal-to-noise observations from the Ultraviolet and Visual Echelle Spectrograph Paranal Observatory Project (UVES-POP) are used to study the interstellarmolecular lines CN (3874 Å), CH⁺ (3957, 4232 Å) and CH (3886, 4300 Å) towards 74 O- and B-type stellar sightlines. Additionally, archive data are presented for 140 ELODIE early-type stellar sightlines at R = 42 000, plus 25 FEROS at R = 48 000 and 3 UVES at R > 50 000, mainly in the CH⁺ (4232 Å) and CH (3886, 4300 Å) transitions. Detection rates are ~45 per cent for CN and ~67 per cent for the other lines in the POP sample, and ~10-15 per cent for CH⁺ and CH lines in the additional sample. CH and CH⁺ are well correlated between log[N(CH) cm^-2]~12-14, implying that these clouds are CH⁺-like CH and not CN-like CH. CH is also very well correlated with Na I D in the range log[N(Na I cm^-2]) ~12.2-14.2. A few sightlines show tentative velocity shifts of ~2 km s^-1 between CH and CH⁺, which appear to be caused by differences in component strength in blends, and hence do not provide firm evidence for shocks. Finally, we describe a search for ¹³CH⁺ in a sightline towards HD 76341. No ¹³CH⁺ is detected, placing a limit on the ¹³CH⁺ to ¹²CH⁺ ratio of ~0.01. If a formal fit is attempted, the equivalent width ratio in the two isotopes is a factor ~90 but with large errors. 

Energy levels, radiative rates, and electron impact excitation rates for transitions in Li-like ions with 21≤Z≤28

We report calculations of energy levels, radiative rates, and electron impact excitation rates for transitions in Li-like ions with 21≤Z≤28. The General-Purpose Relativistic Atomic Structure Package is adopted for calculating energy levels and radiative rates, while for determining the collision strengths and subsequently the excitation rates, the Dirac Atomic R-matrix Code is used. Oscillator strengths, radiative rates, and line strengths are listed for all E1, E2, M1, and M2 transitions among the lowest 24 levels of the Li-like ions considered. Collision strengths have been averaged over a Maxwellian velocity distribution, and the effective collision strengths obtained are given over a wide temperature range up to 10^7.8 K. Additionally, lifetimes are listed for all calculated levels of these ions. Finally, extensive comparisons are made with results available in the literature, as well as with our analogous calculations for all parameters with the Flexible Atomic Code, in order to assess the accuracy of the results.

Photocatalytic activity indicator inks for the probing a wide range of surfaces

Three photocatalyst inks based on the redox dyes, Resazurin (Rz), Basic Blue 66 (BB66) and Acid Violet 7 (AV7), are used to assess the photocatalytic activities of a variety of different materials, such as commercial paint, tiles and glass and laboratory made samples of sol–gel coated glass and paint, which collectively exhibit a wide range of activities that cannot currently be probed by any one of the existing ISO tests. Unlike the ISO tests, the ink tests are fast (typically <10 min), simple to employ and inexpensive. Previous work indicates that the Rz ink test at least correlates linearly with other photocatalytic tests such as the photomineralisation of stearic acid. The average time to bleach 90% of the key RGB colour component of the ink, red for Rz and BB66 inks and green for AV7 ink, is determined, ttb(90), for eight samples of each of the different materials tested. Five laboratories conducted the tests and the results revealed an average repeatability and reproducibility of: ca. 11% and ca 21%, respectively, which compare well with those reported for the current ISO tests. Additional work on commercial self-cleaning glass using an Rz ink showed that the change in the red component of the RGB image of the ink correlated linearly with that of the change of absorbance at 608 nm, as measured using UV/vis spectroscopy, and the change in the a* component of the Lab colour analysis of the ink, as measured using diffuse reflectance spectroscopy. As a consequence, all three methods generate the same ttb(90). The advantages of the RGB digital image analysis method are discussed briefly.

Musculoskeletal (MSK) and Sport and Exercise Medicine (SEM) in General Practice (GP): A Novel GP-based clinic

The problem-Musculoskeletal (MSK) symptoms are common within primary care but some GPs are not comfortable managing these; waiting times for hospital appointments are a major cause of patients’ complaints. Current UK healthcare policies emphasise a need for more community-based management. We aimed to pilot an innovative general practice-based clinic to improve the management of MSK and Sport and Exercise Medicine (SEM) symptoms within general practice.

The approach-This project was conducted in an inner-city practice of approximately 9,000 patients and 5 GP partners. The practice commissioned a novel monthly 4-hour clinic staffed by one GP with a specialist interest in MSK and SEM conditions. Each patient was allocated a 20-minute appointment. All primary care staff within the practice could refer any patient for whom they considered hospital referral appropriate, with no specific exclusion criteria. Management plans included injection therapy, exercise prescription and onward referral. After three months (August-October 2014) numbers of consultations, sources of referral, reasons for referral and management outcomes were described; patient satisfaction was assessed by questionnaire, offered to 10 randomly selected patients by reception staff and self-completed by patients. Costs of the clinic were compared to current options.

Findings- All patients (14 males; 21 females; aged 35-77 years), were seen within four weeks of referral (one third of orthopaedic referrals in 2013 waited over 9 weeks for appointment). Most were referred from other GPs; some came from physiotherapy and podiatry. Shoulder problems were the most frequent reason for referral. The commonest management option was steroid injection, with most patients being given advice regarding exercise and analgesia; there were 3 onward referrals (2 physiotherapy; 1 rheumatology).

Comparing August-October data in 2014 and 2013, total, orthopaedic and rheumatology referrals were reduced by 147, 2 and 3, respectively; within the practice MSK presentations and physiotherapy and x-ray referrals were 60, 47 and 90 fewer, respectively.

The cost per attendance at the clinic was £61; initial orthopaedic-ICAT assessments cost £82 and a consultant appointment £213.

Satisfaction questionnaires were returned by all 10 selected participants and provided positive feedback, expressing preference for community-based, rather than hospital, management.

Consequence- Our pilot study indicates that this novel service model has potential for efficient and effective management of MSK and SEM complaints in primary care, reducing the need for hospital referral and the clinical burden on general practices. The innovation deserves further evaluation in a full-scale trial to determine its generalisability to other practice settings and populations.

Immunological determination of the pharmaceutical diclofenac in environmental and biological samples

A highly sensitive and specific competitive ELISA on 96-microwell plates was developed for the analysis of the nonsteroidal anti-inflammatory drug diclofenac. Within the water cycle in Europe, this is one of the most frequently detected pharmaceutically active compounds. The LOD at a signal-tonoise ratio (S/N) of 3, and the IC ₅₀, were found to be 6 ng/L and 60 ng/L respectively in tap water. In a comparative study using ELISA and GC-MS, diclofenac levels in wastewater from 21 sewage treatment plants were determined and a good correlation between these methods was found (ELISA vs. GCMS: r = 0.70, slope = 0,90, intercept = 0.37, n = 24). An average degradation rate of -25% can be calculated. Labscale-experiments on the elimination of diclofenac in continuous pilot sewage plants revealed a removal rate of only 5% over a period of 13 weeks. In a further study, the ELISA was applied to a number of extracts of various animal tissues from a range of species, and again a very good relationship between ELISA and LC-ESI/MS data sets was obtained (r = 0.90, p<0.0001; n = 117). The ELISA has proven to be a simple, rapid, reliable and affordable alternative to otherwise costly and advanced techniques for the detection of diclofenac in matrix diverse water samples and tissue extracts after only relatively simple sample preparation. © 2007 American Chemical Society.

Efficacy and safety of ivacaftor in patients with cystic fibrosis who have an Arg117His-CFTR mutation: a double-blind, randomised controlled trial

BACKGROUND: Ivacaftor has been previously assessed in patients with cystic fibrosis with Gly551Asp-CFTR or other gating mutations. We assessed ivacaftor in patients with Arg117His-CFTR, a residual function mutation.

METHODS: We did a 24-week, placebo-controlled, double-blind, randomised clinical trial, which enrolled 69 patients with cystic fibrosis aged 6 years and older with Arg117His-CFTR and percentage of predicted forced expiratory volume in 1 s (% predicted FEV1) of at least 40. We randomly assigned eligible patients (1:1) to receive placebo or ivacaftor 150 mg every 12 h for 24 weeks. Randomisation was stratified by age (6-11, 12-17, and ≥18 years) and % predicted FEV1 (<70, ≥70 to ≤90, and >90). The primary outcome was the absolute change from baseline in % predicted FEV1 through week 24. Secondary outcomes included safety and changes in sweat chloride concentrations and Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain scores. An open-label extension enrolled 65 of the patients after washout; after 12 weeks, we did an interim analysis.

FINDINGS: After 24 weeks, the treatment difference in mean absolute change in % predicted FEV1 between ivacaftor (n=34) and placebo (n=35) was 2·1 percentage points (95% CI -1·13 to 5·35; p=0·20). Ivacaftor treatment resulted in significant treatment differences in sweat chloride (-24·0 mmol/L, 95% CI -28·01 to -19·93; p<0·0001) and CFQ-R respiratory domain (8·4, 2·17 to 14·61; p=0·009). In prespecified subgroup analyses, % predicted FEV1 significantly improved with ivacaftor in patients aged 18 years or older (treatment difference vs placebo: 5·0 percentage points, 95% CI 1·15 to 8·78; p=0·01), but not in patients aged 6-11 years (-6·3 percentage points, -11·96 to -0·71; p=0·03). In the extension study, both placebo-to-ivacaftor and ivacaftor-to-ivacaftor groups showed % predicted FEV1 improvement (absolute change from post-washout baseline at week 12: placebo-to-ivacaftor, 5·0 percentage points [p=0·0005]; ivacaftor-to-ivacaftor, 6·0 percentage points [p=0·006]). We did not identify any new safety concerns. The studies are registered with ClinicalTrials.gov (the randomised, placebo-controlled study, number NCT01614457; the open-label extension study, number NCT01707290).

INTERPRETATION: Although this study did not show a significant improvement in % predicted FEV1, ivacaftor did significantly improve sweat chloride and CFQ-R respiratory domain scores and lung function in adult patients with Arg117His-CFTR, indicating that ivacaftor might benefit patients with Arg117His-CFTR who have established disease.

The novel pyrrolo-1,5-benzoxazepine, PBOX-21, potentiates the apoptotic efficacy of STI571 (imatinib mesylate) in human chronic myeloid leukaemia cells

The Bcr-Abl kinase inhibitor, STI571, is the first line treatment for chronic myeloid leukaemia (CML), but the recent emergence of STI571 resistance has led to the examination of combination therapies. In this report, we describe how a novel non-toxic G1-arresting compound, pyrrolo-1,5-benzoxazepine (PBOX)-21, potentiates the apoptotic ability of STI571 in Bcr-Abl-positive CML cells. Co-treatment of CML cells with PBOX-21 and STI571 induced more apoptosis than either drug alone in parental (K562S and LAMA84) and STI571-resistant cells lines (K562R). This potentiation of apoptosis was specific to Bcr-Abl-positive leukaemia cells with no effect observed on Bcr-Abl-negative HL-60 acute myeloid leukaemia cells. Apoptosis induced by PBOX-21/STI571 resulted in activation of caspase-8, cleavage of PARP and Bcl-2, upregulation of the pro-apoptotic protein Bim and a downregulation of Bcr-Abl. Repression of proteins involved in Bcr-Abl transformation, the anti-apoptotic proteins Mcl-1 and Bcl-(XL) was also observed. The combined lack of an early change in mitochondrial membrane potential, release of cytochrome c and cleavage of pro-caspase-9 suggests that this pathway is not involved in the initiation of apoptosis by PBOX-21/STI571. Apoptosis was significantly reduced following pre-treatment with either the general caspase inhibitor Boc-FMK or the chymotrypsin-like serine protease inhibitor TPCK, but was completely abrogated following pre-treatment with a combination of these inhibitors. This demonstrates the important role for each of these protease families in this apoptotic pathway. In conclusion, our data highlights the potential of PBOX-21 in combination with STI571 as an effective therapy against CML.

Impact of Free Glasses and a Teacher Incentive on Children's Use of Eyeglasses: A Cluster-Randomized Controlled Trial.

Purpose: To study the effect of free glasses combined with teacher incentives on in-school glasses wear among Chinese urban migrant children. Design: Cluster-randomized controlled trial. Methods: Children with VA <= 6/12 in either eye due to refractive error in 94 randomly-chosen primary schools underwent randomization by school to receive free glasses, education on their use and a teacher incentive (Intervention), or glasses prescriptions only (Control). Intervention group teachers received a tablet computer if >= 80% of children given glasses wore them during un-announced visits 6 weeks and 6 months (main outcome) after intervention. Results: Among 4376 children, 728 (16.7%, mean age 10.9 years, 51.0% boys) met enrollment criteria and were randomly allocated, 358 (49.2%, 47 schools) to Intervention and 370 (50.8%, 47 schools) to Control. Among these, 693 children (95.2%) completed the study and underwent analysis. Spectacle wear was significantly higher at 6 months among Intervention children (Observed [main outcome]: 68.3% versus 23.9%, Adjusted Odds Ratio [OR]=11.5, 95% Confidence Interval [CI] 5.91-22.5, P<0.001; Self-reported: 90.6% versus 32.1%, OR = 43.7, 95% CI = 21.7-88.5, P < 0.001). Other predictors of observed wear at 6 months included baseline spectacle wear (P<0.001), uncorrected VA<6/18 (P=0.01) and parental spectacle wear (P=0.02). The 6-month observed wear rate was only 41% among similar-aged children provided free glasses in our previous trial without teacher incentives. Conclusions: Free spectacles and teacher incentives maintain classroom wear in the large majority of children needing glasses over a school year. Low wear among Control children demonstrates the need for interventions.