Protocol for a pilot randomised controlled trial of an intervention to increase the use of traffic light food labelling in UK shoppers (the FLICC trial)

Background: Traffic light labelling of foods—a system that incorporates a colour-coded assessment of the level of total fat, saturated fat, sugar and salt on the front of packaged foods—has been recommended by the UK Government and is currently in use or being phased in by many UK manufacturers and retailers. This paper describes a protocol for a pilot randomised controlled trial of an intervention designed to increase the use of traffic light labelling during real-life food purchase decisions.

Methods/design: The objectives of this two-arm randomised controlled pilot trial are to assess recruitment, retention and data completion rates, to generate potential effect size estimates to inform sample size calculations for the main trial and to assess the feasibility of conducting such a trial. Participants will be recruited by email from a loyalty card database of a UK supermarket chain. Eligible participants will be over 18 and regular shoppers who frequently purchase ready meals or pizzas. The intervention is informed by a review of previous interventions encouraging the use of nutrition labelling and the broader behaviour change literature. It is designed to impact on mechanisms affecting belief and behavioural intention formation as well as those associated with planning and goal setting and the adoption and maintenance of the behaviour of interest, namely traffic light label use during purchases of ready meals and pizzas. Data will be collected using electronic sales data via supermarket loyalty cards and web-based questionnaires and will be used to estimate the effect of the intervention on the nutrition profile of purchased ready meals and pizzas and the behavioural mechanisms associated with label use. Data collection will take place over 48 weeks. A process evaluation including semi-structured interviews and web analytics will be conducted to assess feasibility of a full trial.

Discussion: The design of the pilot trial allows for efficient recruitment and data collection. The intervention could be generalised to a wider population if shown to be feasible in the main trial.

The impact of an educational DVD on pregnant women with gestational diabetes mellitus: a randomised controlled trial

Background The diagnosis of gestational diabetes (GDM) during pregnancy can lead to anxiety. Little research has focused on the education these women receive and how this is best delivered in a busy clinic. Aim This study evaluated the impact of an innovative patient-centred educational DVD on anxiety and glycaemic control and in newly diagnosed women with GDM. Method 150 multi-ethnic women, aged 19-44 years, from three UK hospitals were randomised to either standard care plus DVD (DVD group, n=77) or standard care alone (control group, n=73) at GDM diagnosis. Women were followed up at their next clinic visit at a mean ± SD of 2.5 ± 1.6 weeks later. Primary outcomes were anxiety (State-Trait Anxiety Inventory) and mean 1-hour postprandial capillary self-monitored blood glucose for all meals, on day prior to follow-up. Secondary outcomes included pregnancy specific stress (Pregnancy Distress Questionnaire), emotional adjustment to diabetes (Appraisal of Diabetes Scale), self-efficacy (Diabetes Empowerment Scale) and GDM knowledge (non-validated questionnaire). Other outcomes included mean fasting and 1-hour postprandial blood glucose at each meal, on day prior to follow-up. Women in the DVD group completed a feedback questionnaire on the resource. Results No significant difference between the DVD and control group were reported, for anxiety (37.7 ± 11.7 vs 36.2 ± 10.9; mean difference after adjustment for covariates (95%CI) 2.5 (-0.8, 5.9) or for mean 1-hour postprandial glucose (6.9 ± 0.9 vs 7.0 ± 1.2 mmol/L; -0.2 (-0.5, 0.2). Similarly, no significant differences in the other psychosocial variables were identified between the groups. However, the DVD group had significantly lower postprandial breakfast glucose compared to the control group (6.8 ± 1.2 vs 7.4 ± 1.9 mmol/L; -0.5 (-1.1, -<0.1; p=0.04). Using a scale of 0-10, 84% rated the DVD 7 or above for usefulness (10 being very useful), and 88% rated it 7 or above when asked if they would recommend to a friend (10 being very strongly recommend). Women described the DVD as ‘reassuring’, ‘a fantastic tool’, that ‘provided a lot of information in a quick and easy way’ and ‘helped reinforce all the information from clinic’. Discussion While no significant change was observed in anxiety or mean postprandial glucose, the DVD was rated highly by women with GDM and may be a useful resource to assist with educating newly diagnosed women. This project is supported by BRIDGES, an IDF programme supported by an educational grant from Lilly Diabetes.

Data on carotid intima-media thickness and lipoprotein subclasses in type 1 diabetes from the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC)

Type 1 diabetes (T1DM) is associated with increased risk of macrovascular complications. We examined longitudinal associations of serum conventional lipids and nuclear magnetic resonance (NMR)-determined lipoprotein subclasses with carotid intima-media thickness (IMT) in adults with T1DM (n=455) enrolled in the Diabetes Control and Complications Trial (DCCT). Data on serum lipids and lipoproteins were collected at DCCT baseline (1983-89) and were correlated with common and internal carotid IMT determined by ultrasonography during the observational follow-up of the DCCT, the Epidemiology of Diabetes Interventions and Complications (EDIC) study, at EDIC 'Year 1' (199-1996) and EDIC 'Year 6' (1998-2000). This article contains data on the associations of DCCT baseline lipoprotein profiles (NMR-based VLDL & chylomicrons, IDL/LDL and HDL subclasses and 'conventional' total, LDL-, HDL-, non-HDL-cholesterol and triglycerides) with carotid IMT at EDIC Years 1 and 6, stratified by gender. The data are supplemental to our original research article describing detailed associations of DCCT baseline lipids and lipoprotein profiles with EDIC Year 12 carotid IMT (Basu et al. in press) [1].

The Impact of Multimedia Education on Uptake of Comprehensive Eye Examinations in Rural China: A Randomized, Controlled Trial

PURPOSE: To study the effect of multimedia education on acceptance of comprehensive eye examinations (CEEs), critical for detecting glaucoma and diabetic eye disease, among rural Chinese patients using a randomized, controlled design.
METHODS: Patients aged ≥40 years were recruited from 52 routine clinic sessions (26 intervention, 26 control) conducted at seven rural hospitals in Guangdong, China. Subjects answered demographic questionnaires, were tested on knowledge about CEEs and chronic eye disease, and were told the cost of examination (range US$0-8). At intervention sessions, subjects were cluster-randomized to view a 10-minute video on the value of CEEs and retested. Control subjects were not retested. Trial outcomes were acceptance of CEEs (primary outcome) and final knowledge scores (secondary outcome).
RESULTS: At baseline, >70% (p = 0.70) of both intervention (n = 241, 61.2 ± 12.3 years) and control (n = 218, 58.4 ± 11.7 years) subjects answered no knowledge questions correctly, but mean scores on the test (maximum 5 points) increased by 1.39 (standard deviation 0.12) points (p < 0.001) after viewing the video. Intervention (73.0%) and control (72.9%) subjects did not differ in acceptance of CEEs (p > 0.50). In mixed-effect logistic regression models, acceptance of CEEs was associated with availability of free CEEs (odds ratio 18.3, 95% confidence interval 1.32-253.0), but not group assignment or knowledge score. Acceptance was 97.5% (79/81) when free exams were offered.
CONCLUSIONS: Education increased knowledge about but not acceptance of CEEs, which was generally high. Making CEEs free could further increase acceptance.

Effect of providing free glasses on children's educational outcomes in China: cluster randomized controlled trial

Objective: To assess the effect of provision of free glasses on academic performance in rural Chinese children with myopia. Design: Cluster randomized, investigator masked, controlled trial.Setting 252 primary schools in two prefectures in western China, 2012-13. Participants: 3177 of 19 934 children in fourth and fifth grades (mean age 10.5 years) with visual acuity <6/12 in either eye without glasses correctable to >6/12 with glasses. 3052 (96.0%) completed the study.Interventions Children were randomized by school (84 schools per arm) to one of three interventions at the beginning of the school year: prescription for glasses only (control group), vouchers for free glasses at a local facility, or free glasses provided in class. Main outcome measures: Spectacle wear at endline examination and end of year score on a specially designed mathematics test, adjusted for baseline score and expressed in standard deviations. Results: Among 3177 eligible children, 1036 (32.6%) were randomized to control, 988 (31.1%) to vouchers, and 1153 (36.3%) to free glasses in class. All eligible children would benefit from glasses, but only 15% wore them at baseline. At closeout glasses wear was 41% (observed) and 68% (self reported) in the free glasses group, and 26% (observed) and 37% (self reported) in the controls. Effect on test score was 0.11 SD (95% confidence interval 0.01 to 0.21) when the free glasses group was compared with the control group. The adjusted effect of providing free glasses (0.10, 0.002 to 0.19) was greater than parental education (0.03, −0.04 to 0.09) or family wealth (0.01, −0.06 to 0.08). This difference between groups was significant, but was smaller than the prespecified 0.20 SD difference that the study was powered to detect. Conclusions: The provision of free glasses to Chinese children with myopia improves children’s performance on mathematics testing to a statistically significant degree, despite imperfect compliance, although the observed difference between groups was smaller than the study was originally designed to detect. Myopia is common and rarely corrected in this setting. Trial Registration: Current Controlled Trials ISRCTN03252665.

Effectiveness of a short message reminder in increasing compliance with pediatric cataract treatment:A randomized trial

Objective: Regular follow-up is essential to successful management of childhood cataract. We sought to assess whether a mobile phone short message service (SMS) for parents of children with cataract could improve follow-up adherence and the proportion of procedures performed in timely fashion. Design: Randomized, controlled trial. This trial is registered with ClinicalTrials.gov, NCT01417819. Participants: We included 258 parent-child pairs involved in the Childhood Cataract Program of the Chinese Ministry of Health. Methods: Participants were randomized (1:1) to a mobile phone SMS intervention or standard follow-up appointments. All participants were scheduled to attend <4 follow-up appointments according to the protocol. Parents in the intervention group received SMS automated reminders before scheduled appointments. The control group parents did not receive SMSs or any alternative reminder of scheduled appointments. Regular ocular examinations and analyses were performed by investigators masked to group allocation; however, study participants and the manager in charge of randomization and sending SMSs were not masked. Main Outcome Measures: Number of follow-up appointments attended, additional surgeries, laser treatments, changes in eyeglasses prescription, and occurrence of secondary ocular hypertension. Results: Among parent-child participants, 135 were randomly assigned to the SMS intervention and 123 to standard appointments. Attendance rates for the SMS group (first visit, 97.8%; second, 91.9%; third, 92.6%; fourth, 83%) were significantly higher than those for the control group (first visit, 87.8%; second, 69.9%; third, 56.9%; fourth, 33.3%). The increase in attendance rate for total number of follow-up visits with SMS reminders was 47.2% (relative risk [RR] for attendance, 1.47; 95% confidence interval [CI], 1.16-1.78; P = 0.003). The number needed to remind (NNR) to gain 1 additional visit by 1 child was 3 (95% CI, 1.8-4.2). A total of 247 clinical interventions were carried out in the SMS group and 134 in the control group (RR, 1.68; 95% CI, 1.37-1.99; P = 0.007). The NNR to result in 1 additional clinical intervention was 5 (95% CI, 3.5-6.5). Conclusions: The SMS reminders significantly improved follow-up adherence in pediatric cataract treatment. Using readily available mobile phone resources may be an effective and economic strategy to improve management of childhood cataract in China. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. © 2012 American Academy of Ophthalmology.

A randomized, controlled trial of an intervention promoting cataract surgery acceptance in Rural China:The Guangzhou uptake of surgery trial (GUSTO)

PURPOSE. To evaluate an educational intervention promoting acceptance of cataract surgery in rural China using a randomized controlled design. METHODS. Patients aged 50 years or older with presenting visual acuity (PVA) less than 6/18 in one or both eyes due to cataract were recruited from 26 screening sessions (13 intervention, 13 control) conducted by five rural hospitals in Guangdong, China. At intervention sessions, subjects were shown a 5- minute informational video, and counseled about cataract, surgery, and surgical cost. During screening, all subjects answered questionnaires on knowledge and attitudes about cataract, their finances, and transportation, and were referred for definitive examination if eligible. Study outcomes were acceptance of surgery (principal outcome) and hospital followup. RESULTS. Subjects in the intervention group were younger than controls (P = 0.01), but the groups did not otherwise differ. Among 212 intervention patients and 222 controls, no differences in knowledge and attitude regarding cataract were found. Surgery was accepted by 31.1% of intervention patients and 34.2% of controls (P > 0.50). Predictors of acceptance included younger age, worse logMAR PVA, knowing that cataract can be treated surgically only, greater anticipated loss in income from hospitalization, and greater house floor space per person. Membership in the intervention group was not associated with accepting surgery (odds ratio [OR]=1.11, 95% confidence interval [CI] 0.67-1.84) or hospital follow-up (OR= 1.03, 95% CI = 0.63-1.67). CONCLUSIONS. Educational interventions that successfully impart the knowledge that cataract can be only treated surgically may be more effective in increasing uptake in this setting. © 2012 The Association for Research in Vision and Ophthalmology, Inc.

Visual symptoms and retinal straylight after laser peripheral iridotomy: the Zhongshan Angle-Closure Prevention Trial.

OBJECTIVE: To assess the impact of laser peripheral iridotomy (LPI) on forward-scatter of light and subjective visual symptoms and to identify LPI parameters influencing these phenomena. DESIGN: Cohort study derived from a randomized trial, using an external control group. PARTICIPANTS: Chinese subjects initially aged 50 or older and 70 years or younger with bilateral narrow angles undergoing LPI in 1 eye selected at random, and age- and gender-matched controls. METHODS: Eighteen months after laser, LPI-treated subjects underwent digital iris photography and photogrammetry to characterize the size and location of the LPI, Lens Opacity Classification System III cataract grading, and measurement of retinal straylight (C-Quant; OCULUS, Wetzlar, Germany) in the treated and untreated eyes and completed a visual symptoms questionnaire. Controls answered the questionnaire and underwent straylight measurement and (in a random one-sixth sample) cataract grading. MAIN OUTCOME MEASURES: Retinal straylight levels and subjective visual symptoms. RESULTS: Among 230 LPI-treated subjects (121 [58.8%] with LPI totally covered by the lid, 43 [19.8%] with LPI partly covered by the lid, 53 [24.4%] with LPI uncovered by the lid), 217 (94.3%) completed all testing, as did 250 (93.3%) of 268 controls. Age, gender, and prevalence of visual symptoms did not differ between treated subjects and controls, although nuclear (P<0.01) and cortical (P = 0.03) cataract were less common among controls. Neither presenting visual acuity nor straylight score differed between the treated and untreated eyes among all treated persons, nor among those (n = 96) with LPI partially or totally uncovered. Prevalence of subjective glare did not differ significantly between participants with totally covered LPI (6.61%; 95% confidence interval [CI], 3.39%-12.5%), partially covered LPI (11.6%; 95% CI, 5.07%-24.5%), or totally uncovered LPI (9.43%; 95% CI, 4.10%-10.3%). In regression models, only worse cortical cataract grade (P = 0.01) was associated significantly with straylight score, and no predictors were associated with subjective glare. None of the LPI size or location parameters were associated with straylight or subjective symptoms. CONCLUSIONS: These results suggests that LPI is safe regarding measures of straylight and visual symptoms. This randomized design provides strong evidence that treatment programs for narrow angles would be unlikely to result in important medium-term visual disability.

Ophthalmology. 2011 Dec;118(12):2343-50. doi: 10.1016/j.ophtha.2011.06.016. Epub 2011 Sep 1. Randomized, controlled trial of an educational intervention to promote spectacle use in rural China: the see well to learn well study.

OBJECTIVE: To test an educational intervention promoting the purchase of spectacles among Chinese children. DESIGN: Randomized, controlled trial. PARTICIPANTS: Children in years 1 and 2 of all 20 junior and senior high schools (ages 12-17 years) in 3 rural townships in Guangdong, China. METHODS: Children underwent visual acuity (VA) testing, and parents of participants with presenting VA worse than 6/12 in either eye improving by more than 2 lines with cycloplegic refraction were recommended to purchase glasses. Children at 10 randomly selected schools received a lecture, video, and classroom demonstration promoting spectacle purchase. MAIN OUTCOME MEASURES: Self-reported purchase of spectacles (primary outcome) and observed wear or possession of newly purchased glasses (secondary outcome) at follow-up examinations (mean, 219 ± 87 days after the baseline visit). RESULTS: Among 15 404 eligible children, examinations were completed for 6379 (74.6%) at intervention schools and 5044 (73.6%) at control schools. Spectacles were recommended for 2236 (35.1%) children at intervention schools and for 2212 (43.9%) at control schools. Of these, 417 (25.7%) intervention schools children and 537 (34.0%, P = 0.45) control schools children reported buying glasses. Predictors of purchase in regression models included female gender (P = 0.02), worse uncorrected VA (P < 0.001), and higher absolute value of refractive error (P = 0.001). Neither the rate of self-reported purchase of glasses or observed wear or possession of newly purchased glasses differed between control schools and intervention schools in mixed-effect logistic regression models. Among children not purchasing glasses, 21.7% had better-eye VA of worse than 6/18. CONCLUSIONS: An intervention based on extensive pilot testing and focus groups in the area failed to promote spectacle purchase or wear. The high burden of remaining uncorrected poor vision underscores the need to develop better interventions. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The Northern Ireland Assembly Election 2011

Following the first full term of regional government in the province since 1972, the Northern Ireland Assembly election held on 5 May 2011 saw the continuation of several trends. Foremost, the Democratic Unionist Party and Sinn Féin bolstered further their positions as leaders of their respective communities, with the Social Democratic and Labour Party and Ulster Unionist Party losing yet more ground. Building on their decision to enter power-sharing government together in 2007, the two largest parties framed themselves as the progressive choice for voters. As this was the first Assembly election since St Andrews (2006), much of the campaign dialogue centred on the prospect of a Sinn Féin First Minister, a concern highlighted by both unionist parties. The campaign also focused on ‘normal’ socio-economic political issues and possible institutional reform. The absence of inter-party conflict led to the campaign being perceived as the most mundane in living memory, with fears of a record low turnout realised.

Effects of a book gifting programme on literacy outcomes for foster children: A randomised controlled trial evaluation of the Letterbox Club in Northern Ireland

The poor educational outcomes of children in care is a significant concern internationally. Whilst there have been many interventions developed to address this problem, very few of these have been rigorously evaluated. This article presents the findings of a randomised controlled trial that sought to measure the effectiveness of a book gifting programme (the Letterbox Club) that aims to improve literacy skills amongst children aged 7-11 years in foster care. The programme involves children receiving six parcels of books sent through the post over a six-month period. The trial, which ran between April 2013 and June 2014, involved a sample of 116 children in Northern Ireland (56 randomly allocated to the intervention group and 60 to a waiting list control group). Outcome measures focused on reading skills (reading accuracy, comprehension and rate) and attitudes to reading and school. The trial found no evidence that the book-gifting programme had any effect on any of the outcomes measured. Drawing upon some of the emergent themes from the accompanying qualitative process evaluation that sought to determine foster carer/child attitude towards and engagement with the parcels, it is suggested that one plausible reason for the ineffectiveness of the Letterbox Club, as intimated by carers and children (rather than explicitly explored with them), is the lack of support provided to the carers/children in relation to the packs received. Reflective of an ecological model of children’s development, it is recommended that for book-gifting programmes to be effective they need to include a focus on encouraging the direct involvement of foster carers in shared literacy activities with the children using the books that are gifted.

Transfusion and Treatment of severe anaemia in African children (TRACT): a study protocol for a randomised controlled trial

BACKGROUND: In sub-Saharan Africa, where infectious diseases and nutritional deficiencies are common, severe anaemia is a common cause of paediatric hospital admission, yet the evidence to support current treatment recommendations is limited. To avert overuse of blood products, the World Health Organisation advocates a conservative transfusion policy and recommends iron, folate and anti-helminthics at discharge. Outcomes are unsatisfactory with high rates of in-hospital mortality (9-10 %), 6-month mortality and relapse (6 %). A definitive trial to establish best transfusion and treatment strategies to prevent both early and delayed mortality and relapse is warranted.

METHODS/DESIGN: TRACT is a multicentre randomised controlled trial of 3954 children aged 2 months to 12 years admitted to hospital with severe anaemia (haemoglobin < 6 g/dl). Children will be enrolled over 2 years in 4 centres in Uganda and Malawi and followed for 6 months. The trial will simultaneously evaluate (in a factorial trial with a 3 x 2 x 2 design) 3 ways to reduce short-term and longer-term mortality and morbidity following admission to hospital with severe anaemia in African children. The trial will compare: (i) R1: liberal transfusion (30 ml/kg whole blood) versus conservative transfusion (20 ml/kg) versus no transfusion (control). The control is only for children with uncomplicated severe anaemia (haemoglobin 4-6 g/dl); (ii) R2: post-discharge multi-vitamin multi-mineral supplementation (including folate and iron) versus routine care (folate and iron) for 3 months; (iii) R3: post-discharge cotrimoxazole prophylaxis for 3 months versus no prophylaxis. All randomisations are open. Enrolment to the trial started September 2014 and is currently ongoing. Primary outcome is cumulative mortality to 4 weeks for the transfusion strategy comparisons, and to 6 months for the nutritional support/antibiotic prophylaxis comparisons. Secondary outcomes include mortality, morbidity (haematological correction, nutritional and infectious), safety and cost-effectiveness.

DISCUSSION: If confirmed by the trial, a cheap and widely available 'bundle' of effective interventions, directed at immediate and downstream consequences of severe anaemia, could lead to substantial reductions in mortality in a substantial number of African children hospitalised with severe anaemia every year, if widely implemented.

Effective collision strengths for election impact excitation of Cl III

Effective collision strengths for electron-impact excitation of the phosphorus-like ion Cl III are presented for all fine-structure transitions among the levels arising from the lowest 23 LS states. The collisional cross sections are computed in the multichannel close-coupling R-matrix approximation, where sophisticated configuration-interaction wave functions are used to represent the target states. The 23 LS states are formed from the basis configurations 3s²3p³, 3s3p⁴, 3s²3p²3d, and 3s²3p²4s, and correspond to 49 fine-structure levels, leading to a total possible 1176 fine-structure transitions. The effective collision strengths, obtained by averaging the electron collision strengths over a Maxwellian distribution of electron velocities, are tabulated in this paper for all 1176 transitions and for electron temperatures in the ranges T(K)=7500-25,000 and log T(K)=4.4-5.4. The former range encompasses the temperatures of particular importance for application to gaseous nebulae, while the latter range is more applicable to the study of solar and laboratory-type plasmas. © 2001 Academic Press.

Do Cochrane summaries help student midwives understand the findings of Cochrane systematic reviews: the BRIEF randomised trial

BACKGROUND: Abstracts and plain language summaries (PLS) are often the first, and sometimes the only, point of contact between readers and systematic reviews. It is important to identify how these summaries are used and to know the impact of different elements, including the authors' conclusions. The trial aims to assess whether (a) the abstract or the PLS of a Cochrane Review is a better aid for midwifery students in assessing the evidence, (b) inclusion of authors' conclusions helps them and (c) there is an interaction between the type of summary and the presence or absence of the conclusions.

METHODS: Eight hundred thirteen midwifery students from nine universities in the UK and Ireland were recruited to this 2 × 2 factorial trial (abstract versus PLS, conclusions versus no conclusions). They were randomly allocated to one of four groups and asked to recall knowledge after reading one of four summary formats of two Cochrane Reviews, one with clear findings and one with uncertain findings. The primary outcome was the proportion of students who identified the appropriate statement to describe the main findings of the two reviews as assessed by an expert panel.

RESULTS: There was no statistically significant difference in correct response between the abstract and PLS groups in the clear finding example (abstract, 59.6 %; PLS, 64.2 %; risk difference 4.6 %; CI -0.2 to 11.3) or the uncertain finding example (42.7 %, 39.3 %, -3.4 %, -10.1 to 3.4). There was no significant difference between the conclusion and no conclusion groups in the example with clear findings (conclusions, 63.3 %; no conclusions, 60.5 %; 2.8 %; -3.9 to 9.5), but there was a significant difference in the example with uncertain findings (44.7 %; 37.3 %; 7.3 %; 0.6 to 14.1, p = 0.03). PLS without conclusions in the uncertain finding review had the lowest proportion of correct responses (32.5 %). Prior knowledge and belief predicted student response to the clear finding review, while years of midwifery education predicted response to the uncertain finding review.

CONCLUSIONS: Abstracts with and without conclusions generated similar student responses. PLS with conclusions gave similar results to abstracts with and without conclusions. Removing the conclusions from a PLS with uncertain findings led to more problems with interpretation.

Immune-derived PD-L1 gene expression defines a subgroup of stage II/III colorectal cancer patients with favorable prognosis that may be harmed by adjuvant chemotherapy

A recent phase 2 study of metastatic colorectal carcinoma (CRC) patients showed that mismatch repair gene status was predictive of clinical response to PD-1-targeting immune checkpoint blockade. Further examination revealed strong correlation between PD-L1 protein expression and microsatellite instability (MSI) in stage IV CRC, suggesting that the amount of PD-L1 protein expression could identify late stage patients who may benefit from immunotherapy. To assess whether the clinical associations between PD-L1 gene expression and MSI identified in metastatic CRC are also present in stage II/III CRC, we used in silico analysis to elucidate the cell types expressing the PD-L1 gene. We found a significant association of PD-L1 gene expression with MSI in early stage CRC (P < 0.001) and show that unlike in non-CRC tumors, PD-L1 is derived predominantly from the immune infiltrate. We demonstrate that PD-L1 gene expression has positive prognostic value in the adjuvant disease setting (PD-L1low v PD-L1high HR = 9.09; CI, 2.11-39.10). PD-L1 gene expression had predictive value, as patients with high PD-L1 expression appear to be harmed by standard-of-care treatment (HR = 4.95; CI,1.10-22.35). Building on the promising results from the metastatic CRC PD-1-targeting trial, we provide compelling evidence that PD-L1high/MSI/immunehigh stage II/III CRC patients should not receive standard chemotherapy. This conclusion supports the rationale to clinically evaluate this patient subgroup for PD-1 blockade treatment.