STRAWB2 (Stress and Wellbeing After Childbirth): a randomised controlled trial of targeted self-help materials to prevent post-traumatic stress disorder following childbirth.

OBJECTIVES: To test whether providing psychological self-help materials would significantly lower the incidence of post-traumatic stress disorder (PTSD) at 6-12 weeks postnatally. DESIGN: Open-label randomised controlled trial, with blinded outcome assessment. SETTING: Community midwifery services in two National Health Service (NHS) trusts in the North West. SAMPLE: A cohort of 2419 women receiving normal NHS postnatal care. METHODS: Midwives screened women for traumatic birth experience; 678 women who screened positively (28.1%) were randomly allocated to self-help with usual care (n = 336) or to usual care alone (n = 342). The self-help materials were a leaflet and online film designed to prevent the development of PTSD after trauma exposure through explaining how to manage early psychological responses. MAIN OUTCOME MEASURE: The primary outcome was a composite of diagnostic and subdiagnostic PTSD at 6-12 weeks postnatally using the gold-standard Clinician-Administered PTSD Scale (CAPS-5) interview. RESULTS: Of the 678 women correctly randomised plus the nine women randomised in error, 478 (70.5%) were followed up. Diagnostic or subdiagnostic PTSD rates at follow-up did not differ between groups who received self-help (26.7%, 65/243) or usual care alone (26.2%, 64/244) (intention-to-treat analysis: RR 1.02, 95% CI 0.68-1.53). Findings remained consistent in the per-protocol analysis (RR 1.04, 95% CI 0.85-1.27). Women viewed the materials very positively. There were no adverse effects. Health economic micro-costing indicated implementation would be very low cost. CONCLUSIONS: Many women experience a traumatic birth and risk developing PTSD, but self-help strategies without professional support are insufficient and should not be routinely introduced. TWEETABLE ABSTRACT: Self-help information alone does not reduce the number of women developing PTSD after a traumatic childbirth.

A long-lived IL-2 mutein that selectively activates and expands regulatory T cells as a therapy for autoimmune disease.

Susceptibility to multiple autoimmune diseases is associated with common gene polymorphisms influencing IL-2 signaling and Treg function, making Treg-specific expansion by IL-2 a compelling therapeutic approach to treatment. As an in vivo IL-2 half-life enhancer we used a non-targeted, effector-function-silent human IgG1 as a fusion protein. An IL-2 mutein (N88D) with reduced binding to the intermediate affinity IL-2Rßγ receptor was engineered with a stoichiometry of two IL-2N88D molecules per IgG, i.e. IgG-(IL-2N88D)2. The reduced affinity of IgG-(IL-2N88D)2 for the IL-2Rßγ receptor resulted in a Treg-selective molecule in human whole blood pSTAT5 assays. Treatment of cynomolgus monkeys with single low doses of IgG-(IL-2N88D)2 induced sustained preferential activation of Tregs accompanied by a corresponding 10-14-fold increase in CD4+ and CD8+ CD25+FOXP3+ Tregs; conditions that had no effect on CD4+ or CD8+ memory effector T cells. The expanded cynomolgus Tregs had demethylated FOXP3 and CTLA4 epigenetic signatures characteristic of functionally suppressive cells. Humanized mice had similar selective in vivo responses; IgG-(IL-2N88D)2 increased Tregs while wild-type IgG-IL-2 increased NK cells in addition to Tregs. The expanded human Tregs had demethylated FOXP3 and CTLA4 signatures and were immunosuppressive. These results describe a next-generation immunotherapy using a long-lived and Treg-selective IL-2 that activates and expands functional Tregsin vivo. Patients should benefit from restored immune homeostasis in a personalized fashion to the extent that their autoimmune disease condition dictates opening up the possibility for remissions and cures.

Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial.

BACKGROUND: Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. METHODS AND FINDINGS: To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D), a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low) from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39) found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = -0.052, 0.254) and 0.497 × 106 IU/m2 (SE = 0.092, 95% CI = 0.316, 0.678), respectively. On analysis of secondary outcomes, using a highly sensitive IL-2 assay, the observed plasma concentrations of the drug at 90 min exceeded the hypothetical Treg-specific therapeutic window determined in vitro (0.015-0.24 IU/ml), even at the lowest doses (0.040 × 106 and 0.045 × 106 IU/m2) administered. A rapid decrease in Treg frequency in the circulation was observed at 90 min and at day 1, which was dose dependent (mean decrease 11.6%, SE = 2.3%, range 10.0%-48.2%, n = 37), rebounding at day 2 and increasing to frequencies above baseline over 7 d. Teffs, natural killer cells, and eosinophils also responded, with their frequencies rapidly and dose-dependently decreased in the blood, then returning to, or exceeding, pretreatment levels. Furthermore, there was a dose-dependent down modulation of one of the two signalling subunits of the IL-2 receptor, the ß chain (CD122) (mean decrease = 58.0%, SE = 2.8%, range 9.8%-85.5%, n = 33), on Tregs and a reduction in their sensitivity to aldesleukin at 90 min and day 1 and 2 post-treatment. Due to blood volume requirements as well as ethical and practical considerations, the study was limited to adults and to analysis of peripheral blood only. CONCLUSIONS: The DILT1D trial results, most notably the early altered trafficking and desensitisation of Tregs induced by a single ultra-low dose of aldesleukin that resolves within 2-3 d, inform the design of the next trial to determine a repeat dosing regimen aimed at establishing a steady-state Treg frequency increase of 20%-50%, with the eventual goal of preventing T1D. TRIAL REGISTRATION: ISRCTN Registry ISRCTN27852285; ClinicalTrials.gov NCT01827735.

Use of programme budgeting and marginal analysis as a framework for resource reallocation in respiratory care in North Wales, UK.

BACKGROUND: Since the global financial crisis, UK NHS spending has reduced considerably. Respiratory care is a large cost driver for Betsi Cadwaladr University Health Board, the largest health board in Wales. Under the remit of 'prudent healthcare' championed by the Welsh Health Minister, a Programme Budgeting Marginal Analysis (PBMA) of the North Wales respiratory care pathway was conducted. METHODS: A PBMA panel of directors of medicines management, therapies finance, planning, public health and healthcare professionals used electronic voting to establish criteria for decision-making and vote on candidate interventions in which to disinvest and invest. RESULTS: A sum of £86.9 million was spent on respiratory care in 2012-13. Following extensive discussion of 13 proposed candidate interventions facilitated by a chairperson, 4 candidates received recommendations to disinvest, 7 to invest and 2 to maintain current activity. Marginal analysis prioritized mucolytics and high antibiotic prescribing as areas for disinvestment, and medicines waste management and pulmonary rehabilitation for investment. CONCLUSIONS: This exercise demonstrates the potential for health boards to use evidence-based approaches to reach potentially controversial disinvestment and investment decisions. Initial progress has begun with communication from the Medical Director in relation to the disinvestment in mucolytics prescribing and possible redirection of funding options being explored.

Sustained in vivo signaling by long-lived IL-2 induces prolonged increases of regulatory T cells.

Regulatory T cells (Tregs) expressing FOXP3 are essential for the maintenance of self-tolerance and are deficient in many common autoimmune diseases. Immune tolerance is maintained in part by IL-2 and deficiencies in the IL-2 pathway cause reduced Treg function and an increased risk of autoimmunity. Recent studies expanding Tregs in vivo with low-dose IL-2 achieved major clinical successes highlighting the potential to optimize this pleiotropic cytokine for inflammatory and autoimmune disease indications. Here we compare the clinically approved IL-2 molecule, Proleukin, with two engineered IL-2 molecules with long half-lives owing to their fusion in monovalent and bivalent stoichiometry to a non-FcRγ binding human IgG1. Using nonhuman primates, we demonstrate that single ultra-low doses of IL-2 fusion proteins induce a prolonged state of in vivo activation that increases Tregs for an extended period of time similar to multiple-dose Proleukin. One of the common pleiotropic effects of high dose IL-2 treatment, eosinophilia, is eliminated at doses of the IL-2 fusion proteins that greatly expand Tregs. The long half-lives of the IL-2 fusion proteins facilitated a detailed characterization of an IL-2 dose response driving Treg expansion that correlates with increasingly sustained, suprathreshold pSTAT5a induction and subsequent sustained increases in the expression of CD25, FOXP3 and Ki-67 with retention of Treg-specific epigenetic signatures at FOXP3 and CTLA4.

The Effect of Socio-Economic Status on Severity of Periocular Basal Cell Carcinoma at Presentation.

PURPOSE: To evaluate the influence of socio-economic factors on size of periocular basal cell carcinoma at presentation. METHODS: All periocular basal cell carcinoma cases receiving treatment from the oculoplastics team in South Glasgow Hospitals NHS Trust, Glasgow, between 1999 and 2009, were identified retrospectively. Information collected included demographic details of patients, side and site of lesions, type of lesions, and size of lesions. The size of lesion was defined as small for any dimension not exceeding 5 mm, medium for dimensions between 6 mm and 10 mm, and large for dimensions exceeding 11 mm. Home address was used to determine the Scottish Index of Multiple Deprivation rank. The demographics, size of lesion, and Scottish Index of Multiple Deprivation rank were investigated using the general linear regression modelling. RESULTS: Of the 67 cases, 24 were men and 43 were women. The mean age was 71.5 years. There were a total of 67 identified cases, of which 38 presented with small-size lesions, 24 with medium-size lesions, and 5 with large-size lesions. Scottish Index of Multiple Deprivation is related to the presenting incidence of basal cell carcinoma, with the lower ranks presenting more frequently. CONCLUSIONS: Socio-economic deprivation is associated with larger and more frequent presentation of periocular basal cell carcinoma. This highlights the importance of raising awareness among populations of the more deprived areas of the significance of lumps and bumps within the periocular regions.

Quantum flutter: signatures and robustness.

We investigate the motion of an impurity particle injected with finite velocity into an interacting one-dimensional quantum gas. Using large-scale numerical simulations based on matrix product states, we observe and quantitatively analyze long-lived oscillations of the impurity momentum around a nonzero saturation value, called quantum flutter. We show that the quantum flutter frequency is equal to the energy difference between two branches of collective excitations of the model. We propose an explanation of the finite saturation momentum of the impurity based on the properties of the edge of the excitation spectrum. Our results indicate that quantum flutter exists away from integrability and provide parameter regions in which it could be observed in experiments with ultracold atoms using currently available technology.

Micro-costing in public health economics: steps towards a standardized framework, using the incredible years toddler parenting program as a worked example.

Complex interventions, such as parenting programs, are rarely evaluated from a public sector, multi-agency perspective. An exception is the Incredible Years (IY) Basic Parenting Program; which has a growing clinical and cost-effectiveness evidence base for preventing or reducing children's conduct problems. The aim of this paper was to provide a micro-costing framework for use by future researchers, by micro-costing the 12-session IY Toddler Parenting Program from a public sector, multi-agency perspective. This micro-costing was undertaken as part of a community-based randomized controlled trial of the program in disadvantaged Flying Start areas in Wales, U.K. Program delivery costs were collected by group leader cost diaries. Training and supervision costs were recorded. Sensitivity analysis assessed the effects of a London cost weighting and group size. Costs were reported in 2008/2009 pounds sterling. Direct program initial set-up costs were £3305.73; recurrent delivery costs for the program based on eight parents attending a group were £752.63 per child, falling to £633.61 based on 10 parents. Under research contexts (with weekly supervision) delivery costs were £1509.28 per child based on eight parents, falling to £1238.94 per child based on 10 parents. When applying a London weighting, overall program costs increased in all contexts. Costs at a micro-level must be accurately calculated to conduct meaningful cost-effectiveness/cost-benefit analysis. A standardized framework for assessing costs is needed; this paper outlines a suggested framework. In prevention science it is important for decision makers to be aware of intervention costs in order to allocate scarce resources effectively.

Bladder tumor Resection Weight as a Prognostic Factor for Recurrence and Progression in Patients With High-Risk Non-Muscle Invasive Bladder Treated With BCG.

INTRODUCTION: Predicting outcomes of patients with high-risk non-muscle invasive bladder cancer (HR-NMIBC) is critical. Here, we evaluate whether bladder tumor resection weight might serve as a prognostic factor for recurrence and progression of HR-NMIBC patients treated with Bacillus Calmette-Guérin (BCG). METHODS: In this retrospective, single-centre study in the UK, we analysed a consecutive cohort of HR-NMIBC patients who have received adequate intravesical BCG immunotherapy between 2009 and 2019. Univariable and multivariable Cox proportional hazards models were used to assess the association of resection weight and established predictors with recurrence and progression. RESULTS: A total of 187 HR-NMIBC patients were analysed. The median resection weight was 1.4g (range: 0.2-28.5g). Within a median follow-up of 41 months, 58 (31%) tumors recurred and 19 (10%) progressed. Fifty-four patients (29%) died from any cause and 16 (9%) died from bladder cancer. Both the risk of recurrence (P = .007) and progression (P = .019) increased with rising resection weight. On the multivariable analysis, a resection weight of ≥ 2g and ≥ 3g conferred a 4.35-fold and a 9.03-fold increased risk of bladder cancer recurrence (P < .001) and progression (P < .001), respectively. The addition of resection weight improved the C index of multivariable standard prognostic models to a clinically significant extent (+ 3.8% for recurrence, + 4.3% for progression). CONCLUSION: In our HR-NMIBC patient cohort treated with BCG, bladder tumor resection weight was associated with disease recurrence and progression. Its addition improves discrimination of standard prognostic factors. Measurement may therefore be considered for routine clinical practice.

CD56bright natural killer cells preferentially kill proliferating CD4+ T cells.

Human CD56br natural killer (NK) cells represent a small subset of CD56+ NK cells in circulation and are largely tissue-resident. The frequency and number of CD56br NK cells in blood has been shown to increase following administration of low-dose IL-2 (LD-IL2), a therapy aimed to specifically expand CD4+ regulatory T cells (Tregs). Given the potential clinical application of LD-IL-2 immunotherapy across several immune diseases, including the autoimmune disease type 1 diabetes, a better understanding of the functional consequences of this expansion is urgently needed. In this study, we developed an in vitro co-culture assay with activated CD4+ T cells to measure NK cell killing efficiency. We show that CD56br and CD56dim NK cells show similar efficiency at killing activated CD4+ conventional T (Tconv) and Treg cell subsets. However, in contrast to CD56dim cells, CD56br NK cells preferentially target highly proliferative cells. We hypothesize that CD56br NK cells have an immunoregulatory role through the elimination of proliferating autoreactive CD4+ Tconv cells that have escaped Treg suppression. These results have implications for the interpretation of current and future trials of LD-IL-2 by providing evidence for a new, possibly beneficial immunomodulatory mechanism of LD-IL-2-expanded CD56br NK cells.

Diabetic retinopathy screening: perspectives of people with diabetes, screening intervals and costs of attending screening.

AIMS: To obtain the views of people with diabetes about the provision of diabetic retinopathy screening services; and the interval of screening. METHODS: Between October 2009 and January 2010, people with diabetes attending diabetic retinopathy screening clinics across Wales were asked to complete a questionnaire comprising of two parts: the first asking about their health, diabetes history, demographic characteristics and views about the diabetic retinopathy screening service, and the second asking about the costs of attending the screening. RESULTS: The response rate was 40% (n = 621) from 1550 questionnaires distributed at diabetic retinopathy clinics, with 600 complete responses analysed. Respondents had a mean known duration of diabetes of 8.5 years (sd 7.8) and had attended for screening on average 3.2 times (sd 1.6) in the last 5 years. Sixty-eight per cent (n = 408) of respondents reported having their eyes screened approximately once a year. Eighty-five per cent (n = 507) felt that they should have their eyes screened every year. However, 65% (n = 390) of respondents would accept screening at 2- or 3-year intervals if medical evidence showed that it was safe. The reported personal costs incurred by respondents attending diabetic retinopathy screening were low. CONCLUSION: Our study suggests that people with diabetes undergoing diabetic retinopathy screening would accept a greater screening interval, provided that adequate clinical evidence and medical reassurance were given.

Trimers, molecules, and polarons in mass-imbalanced atomic Fermi gases.

We consider the ground state of a single "spin-down" impurity atom interacting attractively with a "spin-up" atomic Fermi gas. By constructing variational wave functions for polarons, molecules, and trimers, we perform a detailed study of the transitions between these dressed bound states as a function of mass ratio r=m↑/m↓ and interaction strength. Crucially, we find that the presence of a Fermi sea enhances the stability of the p-wave trimer, which can be viewed as a Fulde-Ferrell-Larkin-Ovchinnikov molecule that has bound an additional majority atom. For sufficiently large r, we find that the transitions lie outside the region of phase separation of the imbalanced Fermi gas and should thus be observable in experiment, unlike the well-studied equal-mass case.

Parenting interventions: a systematic review of the economic evidence.

Conduct disorder (CD) places huge costs on the individual, family and society. Parenting programmes can reduce CD symptomatology, but economic evaluations of their cost-effectiveness are rarely undertaken. The objective of this paper was to conduct the first specific systematic review of the published economic evidence of parenting programmes as a means to support families with children with or at risk of developing CD. A systematic search of 12 electronic databases was conducted. We identified 93 papers, of which six fulfilled the inclusion criteria. The search found one review article, mainly focusing upon clinical evidence with secondary focus on cost-effectiveness, one cost-effectiveness study, two partial economic evaluations and two cost studies. The costs of group parenting programme delivery ranged from £629.00 to £3839.00. Cost-effectiveness was influenced by intervention type and delivery method, i.e. individual versus group programme. The review highlights a need for a more standardized approach towards the comparison of the cost-effectiveness of parent programmes. In future studies it may be helpful to adopt a 'complex intervention approach', exploring in detail the attribution of cause and effect, the role of socio-economic setting and ripple effects, e.g. benefits to other family members.

Tear physiology of aqueous deficiency and evaporative dry eye.

PURPOSE: To determine the differences in tear physiology between aqueous deficiency dry eye (ADDE) and evaporative dry eye (EDE), and evaluate their utility in diagnosis. METHODS: Fifty-six dry eye patients were classified into 30 ADDE and 26 EDE according to the recently published Dry Eye Workshop criteria. A range of tear physiology measures comprising of tear evaporation, turnover rate (TTR), distribution, volume and osmolarity, and meibomian gland dropout were measured in these patients. The effectiveness of the tests, singly and in combinations, in differentiating between the dry eye subtypes was evaluated by retrospective allocation into groups and by Receiver Operative Characteristics (ROC) curve analysis. RESULTS: Statistically significant differences were seen for TTR and tear evaporation (with lower values for ADDE) between ADDE and EDE, but no significant differences were seen for tear osmolarity, volume, distribution, and meibomian gland dropout scores. Differentiation of ADDE and EDE by a cut-off value of 11%/min for TTR was found to have a sensitivity of 86%, specificity of 75%, positive predictive value 89%, negative predictive value 69%, and overall accuracy 83%. The area under the curve on the ROC curve was 0.83. For tear evaporation, a cut-off of 60 g/mh was found to have a sensitivity of 77%, specificity of 55%, positive predictive value 38%, negative predictive value 80%, and overall accuracy 58% in subtype differentiation. The area under the curve was 0.59 on the ROC curve. The distribution curve of the evaporation rates for ADDE and EDE, showed an overlap coefficient of 0.76 indicating that tear evaporation is within a similar range in these two dry eye subtypes. CONCLUSIONS: Tear turnover is significantly lower in ADDE than EDE, but there is considerable overlap of tear evaporation between the two dry eye subtypes. Tear osmolarity and turn over tests can be conducted sequentially to effectively diagnose dry eye and its subtypes.

Cataract surgery refractive outcomes: representative standards in a National Health Service setting.

BACKGROUND/AIMS: To report refractive outcomes from an National Health Service (NHS) cataract surgery service and assess if results meet suggested benchmark standard. METHODS: Details of all patients undergoing cataract surgery in the Southern General and New Victoria hospitals in Glasgow, UK, between November 2006 and December 2016 were prospectively entered into an electronic database. Patients were reviewed 4 weeks postoperatively in the eye clinic and underwent refraction at their local optometrist prior to this appointment. Surgically uncomplicated cases with in the bag' non-toric intraocular lens implantation were included. Patients with previous laser refractive procedures or failing to achieve 6/12 acuity or better postoperatively were excluded. Proximity to targeted postoperative refraction was documented. RESULTS: Over this 10-year period, 11 083 eyes underwent cataract surgery. Of these, 8943 eyes of 6936 patients (80.69%) met the inclusion criteria and had both target and postoperative outcome refraction recorded. The mean difference between the targeted and outcome refraction was -0.07 D (SD 0.67). The mean absolute error was 0.50 D. Postoperative refraction was within 1 D of target refraction for 7938 eyes (88.76%) and within 0.50 D for 5577 eyes (62.36%). CONCLUSION: Refractive outcomes following routine cataract surgery reported here are well within the targets recommended by the Royal College of Ophthalmologists and European guidelines, but suggest that higher cataract refractive outcome benchmark standards may not yet be a realistic expectation for all NHS units with current biometry practice.

Trimorphism in solid resorcinarenes.

Nonylresorcinarene, in contrast to methylresorcinarene and nonylpyrogallene, exists in three isolable phases: a layer structure, a hexamer and an amorphous phase; the three are in thermal equilibrium.

Spontaneous intraocular lens extrusion in a patient with scleromalacia secondary to herpes zoster ophthalmicus.

We report a case of spontaneous intraocular lens (IOL) extrusion in association with scleromalacia 10 years after uneventful endocapsular surgery. The patient had a history of iridocyclitis secondary to herpes zoster ophthalmicus in the affected eye. A minimally invasive approach involving repositioning the IOL and closure with a conjunctival flap resulted in restoration of visual acuity.

Gamma-linolenic acid supplementation for prophylaxis of atopic dermatitis--a randomized controlled trial in infants at high familial risk.

BACKGROUND: Studies suggest that low concentrations of n-6 long-chain polyenes in early life are correlated to atopic disease in later life. OBJECTIVE: The purpose of the study was to investigate the possible preventive effect of gamma-linolenic acid (GLA) supplementation on the development of atopic dermatitis in infants at risk. DESIGN: In a double-blind, randomized, placebo-controlled trial, formula-fed infants (n = 118) with a maternal history of atopic disease received borage oil supplement (containing 100 mg GLA) or sunflower oil supplement as a placebo daily for the first 6 mo of life. Main outcome measures were the incidence of atopic dermatitis in the first year of life (by UK Working Party criteria), the severity of atopic dermatitis (SCORing Atopic Dermatitis; SCORAD), and the total serum immunoglobulin E (IgE) concentration at the age of 1 y. RESULTS: The intention-to-treat analysis showed a favorable trend for severity of atopic dermatitis associated with GLA supplementation ( x+/- SD SCORAD: 6.32 +/- 5.32) in the GLA-supplemented group as compared with 8.28 +/- 6.54 in the placebo group (P = 0.09; P = 0.06 after adjustment for total serum IgE at baseline, age 1 wk), but no significant effects on the other atopic outcomes. The increase in GLA concentrations in plasma phospholipids between baseline and 3 mo was negatively associated with the severity of atopic dermatitis at 1 y (Spearman's correlation coefficient = -0.233, P = 0.013). There was no significant effect on total serum IgE concentration. CONCLUSION: Early supplementation with GLA in children at high familial risk does not prevent the expression of atopy as reflected by total serum IgE, but it tends to alleviate the severity of atopic dermatitis in later infancy in these children.