Comparison of two multi-trait association testing methods and sequence-based fine mapping of six additive QTL in Swiss Large White pigs.

BACKGROUND: Genetic correlations between complex traits suggest that pleiotropic variants contribute to trait variation. Genome-wide association studies (GWAS) aim to uncover the genetic underpinnings of traits. Multivariate association testing and the meta-analysis of summary statistics from single-trait GWAS enable detecting variants associated with multiple phenotypes. In this study, we used array-derived genotypes and phenotypes for 24 reproduction, production, and conformation traits to explore differences between the two methods and used imputed sequence variant genotypes to fine-map six quantitative trait loci (QTL). RESULTS: We considered genotypes at 44,733 SNPs for 5,753 pigs from the Swiss Large White breed that had deregressed breeding values for 24 traits. Single-trait association analyses revealed eleven QTL that affected 15 traits. Multi-trait association testing and the meta-analysis of the single-trait GWAS revealed between 3 and 6 QTL, respectively, in three groups of traits. The multi-trait methods revealed three loci that were not detected in the single-trait GWAS. Four QTL that were identified in the single-trait GWAS, remained undetected in the multi-trait analyses. To pinpoint candidate causal variants for the QTL, we imputed the array-derived genotypes to the sequence level using a sequenced reference panel consisting of 421 pigs. This approach provided genotypes at 16 million imputed sequence variants with a mean accuracy of imputation of 0.94. The fine-mapping of six QTL with imputed sequence variant genotypes revealed four previously proposed causal mutations among the top variants. CONCLUSIONS: Our findings in a medium-size cohort of pigs suggest that multivariate association testing and the meta-analysis of summary statistics from single-trait GWAS provide very similar results. Although multi-trait association methods provide a useful overview of pleiotropic loci segregating in mapping populations, the investigation of single-trait association studies is still advised, as multi-trait methods may miss QTL that are uncovered in single-trait GWAS.

Biologic drug survival rates in the era of anti-interleukin-17 antibodies: a time-period-adjusted registry analysis.

BACKGROUND: Drug survival rates reflect efficacy and safety and may be influenced by the availability of alternative treatment options. Little is known about time-dependent drug survival in psoriasis and the effect of increasing numbers of biologic treatment options. OBJECTIVES: To determine whether drug survival is influenced by the availability of treatment options and by factors such as gender, psoriatic arthritis or previous biologic treatment. METHODS: This observational, retrospective, multicentre cohort study analysed data from patients registered in the Austrian Psoriasis Registry (PsoRA) who were treated with biologics between 1 January 2015 and 30 November 2019. RESULTS: A total of 1572 patients who received 1848 treatment cycles were included in this analysis. The highest long-term Psoriasis Area and Severity Index improvement was observed after treatment with ixekizumab, followed by ustekinumab and secukinumab, adalimumab and etanercept. Overall, ustekinumab surpassed all other biologics in drug survival up to 48 months. However, when adjusted for biologic naïvety, its superiority vanished and drug survival rates were similar for ixekizumab (91·6%), secukinumab (90·2%) and ustekinumab (92·8%), all of them superior to adalimumab (76·5%) and etanercept (71·9%) at 12 months and beyond. Besides biologic non-naïvety (2·10, P < 0·001), the introduction of a new drug such as secukinumab or ixekizumab (relative hazard ratio 1·6, P = 0·001) and female gender (1·50, P = 0·019) increased the risk of treatment discontinuation overall, whereas psoriatic arthritis did not (1·12, P = 0·21). CONCLUSIONS: The time-dependent availability of drugs should be considered when analysing and comparing drug survival. Previous biologic exposure significantly influences drug survival. Women are more likely to stop treatment.

[Risk factors and management strategies for early and late infections following reconstruction with special tumour endoprostheses]. / Risikofaktoren und Managementstrategien des Früh- und Spätinfektes nach Rekonstruktion mit Tumorspezialendoprothesen.

BACKGROUND: Periprosthetic joint infection (PJI) of megaprostheses occur in about 10% of all cases. The criteria for PJI are defined by the "Musculoskleletal Infection Society" (MSIS) and apply to both primary arthroplasty and megaprostheses. MANAGEMENT: The management strategies of PJI in megaprostheses are dependent on the duration of infection and the maturity of the bacterial biofilm. Implant retention with an exchange of the mobile components is only possible in the presence of an immature biofilm. In the presence of a mature biofilm, a one- or two-stage exchange must be performed. A complete exchange of all endoprosthetic components should be performed, if possible, since a partial retention of isolated components results in inferior treatment success rates. RESULTS: The highest success rates are achievable with two-stage exchanges. Multiple risk factors such as skin necrosis, postoperative haematoma, prolonged wound secretion and operative times ≥ 2.5 h are risk factors for the development of PJI in megaprostheses. Knowledge regarding these risk factors allows for an identification of high-risk patients and early management of PJI.

Effective genetic markers for identifying the Escherichia coli F4ac receptor status of pigs.

The F4ac receptor locus (F4acR), which encodes susceptibility or resistance to Escherichia coli diarrhoea, is inherited as an autosomal recessive monogenetic trait. F4acR is localized on pig chromosome 13 (SSC13q41-q44) near the MUC13 gene. Two flanking markers (CHCF1 and ALGA0106330) with a high linkage disequilibrium (LD) with F4acR were found to be effective for the genetic identification of F4ac-resistant pigs in the Swiss Large White breed (one recombinant out of 2034 genotyped pigs). Three recombinant boars, one each from the Duroc, Swiss Landrace and Piétrain breeds, were genotyped with seven different markers and phenotyped by means of a microscopic adhesion test. Only ALGA0072075, CHCF1 and CHCF3 indicated the correct phenotype. To test the effect of the resistance allele on production traits, 530 Large White pigs from the national test station were investigated. A significant difference existed among the F4acR locus genotypes in the intramuscular fat content of the longissimus dorsi muscle, whereas no other production traits were influenced by the resistance allele. The frequency of the CHCF1-C and ALGA0106330-A alleles associated with resistance in the Swiss Large White population was 60%, which is advantageous for implementing this trait in a breeding programme to select for E. coli F4ac-resistant animals. The selection of resistant pigs should start on the male side due to the inability of resistant sows to produce sufficient amounts of protecting antibodies in the colostrum. Selection of genetically F4ac-resistant pigs is a sustainable and suitable alternative to decreasing animal loss and antibiotic use due to diarrhoea.

Religiosity and psychological resilience in patients with schizophrenia and bipolar disorder: an international cross-sectional study.

OBJECTIVE: The impact of religious/spiritual activities on clinical outcomes in patients with serious mental illnesses remains controversial, which was addressed in this international cross-sectional study. METHOD: Three-hundred sixty-nine subjects were recruited from Austria (n = 189) and Japan (n = 180), consisting of 112 outpatients with paranoid schizophrenia, 120 with bipolar I disorder (DSM-IV), and 137 healthy controls. Religiosity was assessed in terms of attendance and importance of religious/spiritual activities, while resilience was assessed using the 25-item Resilience Scale. General linear models were used to test whether higher religiosity will be associated with higher resilience, higher social functioning, and lower psychopathology. The association between levels of spiritual well-being and resilience was also examined. RESULTS: Attendance of religious services (F[4,365] = 0.827, P = 0.509) and importance of religion/spirituality (F[3,365] = 1.513, P = 0.211) did not show significant associations with resilience. Regarding clinical measures, a modest association between higher importance of religion/spirituality and residual manic symptoms was observed in bipolar patients (F[3,118] = 3.120, P = 0.029). In contrast to the findings regarding religiosity, spiritual well-being showed a strong positive correlation with resilience (r = 0.584, P < 0.001). CONCLUSION: The protective effect of religiosity in terms of resilience, social functioning, and psychopathology was not evident in our sample. Spiritual well-being appears more relevant to resilience than religiosity.

Emotional intelligence and non-social cognition in schizophrenia and bipolar I disorder.

BACKGROUND: The different patterns of Emotional Intelligence (EI) deficits in schizophrenia and bipolar I disorder are are not yet well understood. This study compares EI levels among these groups and highlights the potential impact of non-social cognition on EI. METHOD: Fifty-eight schizophrenia and 60 bipolar outpatients were investigated using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) and the Brief Assessment of Cognition in Schizophrenia (BACS). Analyses of covariance were performed with adjustment for the BACS composite score. RESULTS: Compared to bipolar subjects, schizophrenia patients showed significantly lower levels in both EI and non-social cognition. After adjustment for the BACS composite score, the difference in EI was lost. The mediation analysis revealed that differences between schizophrenia and bipolar patients in strategic EI are almost fully attributable to the mediating effect of non-social cognition. CONCLUSIONS: Our findings suggest that in both schizophrenia and bipolar patients EI is strongly influenced by non-social cognitive functioning. This has to be taken into account when interpreting MSCEIT data in comparative studies in serious mental illness and emphasizes the importance of cognitive remediation.

Quality of life in stabilized patients with schizophrenia is mainly associated with resilience and self-esteem.

OBJECTIVE: Improving quality of life (QoL) is an important objective in the treatment of schizophrenia. The aim of the current study was to examine to what extent resilience, self-esteem, hopelessness, and psychopathology are correlated with QoL. METHOD: We recruited 52 out-patients diagnosed with schizophrenia according to DSM-IV criteria and 77 healthy control subjects from the general community. In patients, psychopathology was quantified by the Positive and Negative Syndrome Scale. The following scales were used in both patients and control subjects: the Berliner Lebensqualitätsprofil, the Resilience Scale, the Rosenberg Self-Esteem Scale, and the Beck Hopelessness Scale to assess QoL, resilience, self-esteem, and hopelessness respectively. RESULTS: Patients with schizophrenia presented with significantly less QoL, resilience, self-esteem, and hope compared to healthy control subjects. In patients, QoL correlated moderately with resilience, self-esteem, and hopelessness and weakly with symptoms. With respect to the latter, particularly depression and positive symptoms were negatively correlated with QoL. CONCLUSION: Our results highlight the complex nature of QoL in patients suffering from schizophrenia. They underscore that significant efforts are necessary to enhance resilience and self-esteem and to diminish hopelessness as well as affective and positive symptoms in patients with schizophrenia.

Economic analysis of two-stage septic revision after total hip arthroplasty: What are the relevant costs for the hospital's orthopedic department?

BACKGROUND: The number of septic total hip arthroplasty (THA) revisions is increasing continuously, placing a growing financial burden on hospitals. Orthopedic departments performing septic THA revisions have no basis for decision making regarding resource allocation as the costs of this procedure for the departments are unknown. It is widely assumed that septic THA procedures can only be performed at a loss for the department. Therefore, the purpose of this study was to investigate whether this assumption is true by performing a detailed analysis of the costs and revenues for two-stage septic THA revision. METHODS: Patients who underwent revision THA for septic loosening in two sessions from January 2009 through March 2012 were included in this retrospective, consecutive cost study from the orthopedic department's point of view. We analyzed variable and case-fixed costs for septic revision THA with special regard to implantation and explantation stay. By using marginal costing approach we neglected hospital-fixed costs. Outcome measures include reimbursement and daily contribution margins. RESULTS: The average direct costs (reimbursement) incurred for septic two-stage revision THA was €10,828 (€24,201). The difference in cost and contribution margins per day was significant (p < .001 and p = 0.019) for ex- and implantation (€4147 vs. €6680 and €429 vs. €306) while length of stay and reimbursement were comparable. CONCLUSIONS: This is the first detailed analysis of the hospital department's cost for septic revision THA performed in two sessions. Disregarding hospital-fixed costs the included variable and case fixed-costs were covered by revenues. This study provides cost data, which will be guidance for health care decision makers.

Psychiatric misdiagnoses in Dandy-Walker variant.

Cases of intellectual impairment and aberrant behavior in patients with cerebellar diseases have been described since the early nineteenth century. Here, we report on a patient suffering from Dandy-Walker variant who presented with symptoms of obsessive compulsive disorder and delusional disorder. The current findings emphasize the potential relevance of focal cerebellar lesions as organic correlates of these disorders.

Mortality attributable to rheumatic heart disease in the Kimberley: a data linkage approach.

BACKGROUND: Acute rheumatic fever (ARF) and its sequelae, rheumatic heart disease (RHD) are now uncommon in the general Australian population. However, these preventable and treatable diseases continue to affect Aboriginal Australians disproportionately, especially in remote communities. In the Kimberley region of Western Australia (WA), the prevalence of RHD is approximately 1% among Aboriginal residents. Yet an accurate and comprehensive picture of RHD-related mortality is lacking. AIM: This study aims to determine the mortality burden attributable to ARF and RHD in the Kimberley using linked hospitalisation and death registry data. METHODS: A retrospective cohort study was undertaken comprising all Kimberley residents with a WA hospital admission for ARF or RHD between 1970 and 2010, linked with the WA Death Register. We manually classified RHD-attributable deaths ('definite' or 'probable') to determine mortality burden. Hospitalisation prior to death, including valvular surgery was also ascertained. RESULTS: There were 35 RHD-attributable deaths in the Kimberley between 1990 and 2010, with 94% occurring in Aboriginal people. Their median age of death was 40 years. The age-standardised RHD annual death rate was 15.6 per 100 000 with a total of 1100 premature years of life lost before age of 75 within this group. Conventional International Classification of Diseases-generated mortality data underestimated mortality burden. CONCLUSION: RHD remains a significant cause of premature mortality for Aboriginal people in the Kimberley, with mortality rates unmatched in the general Australian population since the first half of the 20th century. Efforts to reduce progression of this disease through RHD Register and Control Programs are crucial alongside action to address underlying socioeconomic and environmental inequities.

An economic analysis of aseptic revision hip arthroplasty: calculation of partial hospital costs in relation to reimbursement.

INTRODUCTION: Aseptic loosening is one of the most common intermediate and long-term complications after total hip replacement (THR). These complications cause suffering and require expensive revision surgery. Little concrete data on direct costs are available from the hospital's, moreover operating department's perspective. We here provide a detailed analysis of the costs of THR revision and relate them to reimbursement underlying the German diagnosis-related groups (DRG) system. MATERIALS AND METHODS: Major cost parameters were identified using for orientation the cost matrix of the German Institute for Hospital Reimbursement (InEK GmbH). We then retrospectively analysed the major direct costs of aseptic revision THR in terms of contribution margins I and II. The analysis included a total of 114 patients who underwent aseptic revision from 1 January 2009 to 31 March 2012. Data were retrieved from the hospital information system and patient records. All costs of surgery, diagnostic tests, and other treatments were calculated as purchase prices in EUR. The comparative analysis of direct costs and reimbursements was done for DRG I46A and I46B from the hospital's, especially treating department's rather than the society or healthcare insurance's perspective. RESULTS: The average direct cost incurred by the hospital for a THR revision was 4,380.0. The largest share was accounted for surgical costs (62.7 % of total). Implant and staff costs were identified as the most important factors that can be influenced. The proportion of the daily contribution margin that was left to cover the hospital's indirect cost decreased with the relative cost weight of the DRG to which a patient was assigned. CONCLUSION: Our study for the first time provides a detailed analysis of the major direct case costs of THR revision for aseptic loosening from the provider's perspective. Our findings suggest that these revision operations could be performed cost-beneficially by the operating unit. From an economic perspective, cases with higher cost weights are more favorable for a hospital. These results need to be confirmed in multicenter studies.

Persistence of surface domain structures for a bulk ferroelectric above TC.

Photoemission electron microscopy performed on a well-prepared surface of BaTiO3 reveals the persistence of surface domains at temperatures well above the bulk Curie temperature. Their patterns follow the ferroelectric domain structure observed at 300 K. The contrast between formerly outward polarized domains and in-plane polarized domains is preserved across the transition, while the contrast of inward polarized domains changes sign. The work functions of different possible structures are compared by first-principles calculations. The domain contrast in photoemission above the bulk Curie temperature is associated with a remaining tetragonal distortion of the topmost unit cells which is stabilized by an ionic surface relaxation.

Treatment with 311-nm ultraviolet B enhanced response of psoriatic lesions in ustekinumab-treated patients: a randomized intraindividual trial.

BACKGROUND: Treatment with the interleukin-12/23 antibody ustekinumab produces a satisfactory response [i.e. 75% reduction in Psoriasis Area and Severity Index (PASI) compared with baseline (PASI 75)] in the majority of patients with moderate to severe chronic plaque-type psoriasis. OBJECTIVES: To determine whether concomitant 311-nm ultraviolet (UV) B therapy can further enhance the response in patients with psoriasis treated with ustekinumab. METHODS: Ten patients (five women and five men; mean age 58years, range 48-66) with moderate to severe plaque-type psoriasis were treated with ustekinumab at a standard dosage of 45 or 90mg subcutaneously depending on body weight (below or above 100kg) at weeks 0 and 4. Within 2days after ustekinumab initiation, the minimal erythemal dose (MED) was determined and suberythemal MED 311-nm UVB-based phototherapy was thereafter administered to one randomly selected body half (left or right, excluding the head) three times weekly for 6weeks. Treatment response was monitored weekly in terms of half-body PASI. RESULTS: Nine patients completed the study. Analysis of their data showed that 311-nm UVB significantly accelerated the therapeutic response. At baseline (i.e. start of 311-nm UVB therapy), the mean PASI was similar in both irradiated and unirradiated body halves (13·6 vs. 13·3). At week 6, however, it was lower on irradiated body halves (2·5 vs. 6·1). This difference of 3·6 (95% confidence interval 1·3-5) was statistically significant and corresponded to an overall mean PASI reduction from baseline of 82% vs. 54%, respectively. At week 6, PASI 75 was achieved significantly more often on UV-irradiated body halves than on unirradiated body halves [7/9 patients (78%) vs. 1/9 (11%)] (McNemar test, P=0·007). At week 12, this synergistic effect of 311-nm UVB was still apparent although not significantly so. CONCLUSIONS: Treatment with 311-nm UVB accelerates the clearance of psoriatic lesions in ustekinumab-treated patients.

Molecular characterization of the porcine TEAD3 (TEF-5) gene: examination of a promoter mutation as the causal mutation of a quantitative trait loci affecting the androstenone level in boar fat.

A quantitative trait loci (QTL) for accumulation of androstenone in fat has been identified in an Large White × Meishan cross in a region of SSC7-containing TEAD3. In humans, TEAD3 is a transcription activator, known to be able to regulate the transcription of HSD3B. This enzyme is involved in the degradation of androstenone in the liver. In this study, porcine transcripts of TEAD3 were characterized and compared with mammalian transcripts. The complete structure of porcine TEAD3 gene was characterized including two 5' non-coding exons and one exon 5 not used in porcine transcripts. Variations were screened in sequences related to TEAD3: in exons, in flanking sequences of exons and in the promoter region. A SNP characterized at 726 bp at 5' of the first exon was tested on several pig populations without coherent and convincing results concerning its association with androstenone levels. We showed that in the liver of adult boars, the transcripts levels of TEAD3 and HSD3B were correlated. As in humans, it is possible that HSD3B is a target gene of TEAD3 in porcine liver. Nevertheless, no expression variation was observed for TEAD3 or HSD3B in liver between animals with different genotypes at the SNP. We concluded that this SNP was not the causal mutation of this QTL.

Symptomatic remission and neurocognitive functioning in patients with schizophrenia.

BACKGROUND: A cross-sectional study was conducted in participants with schizophrenia to explore a potential association between the patients' remission status and neurocognitive functioning and to examine whether these factors have an impact on functional outcome. METHOD: Psychopathological symptoms were rated by means of the Positive and Negative Syndrome Scale with symptom remission being assessed by applying the severity component of the recently proposed remission criteria. Tests for the cognitive battery were selected to cover domains known to be impaired in patients with schizophrenia. Next to pre-morbid intelligence, attention performance, executive functioning, verbal fluency, verbal learning and memory, working memory and visual memory were assessed. The joint effect of remission status and neurocognitive functioning on treatment outcome was investigated by logistic regression analysis. RESULTS: Out of 140 patients included in the study, 62 were symptomatically remitted. Mean age, education and sex distribution were comparable in remitted and non-remitted patients. Remitted patients showed significantly higher values on tests of verbal fluency, alertness and optical vigilance. Both symptomatic remission as well as performance on tests of working memory and verbal memory had a significant effect on the patients' employment status. CONCLUSIONS: In the present study neuropsychological measures of frontal lobe functioning were associated with symptomatic remission from schizophrenia. In addition, both symptomatic remission and performance on tests of working memory and verbal memory had a significant effect on the patients' employment status. Longitudinal follow-up data are needed to determine how the associations of these determinants of functional outcome interact and change over time.

Intercellular communication mediated by the extracellular calcium-sensing receptor.

Agonist-evoked, intracellular Ca2+-signalling events are associated with active extrusion of Ca2+ across the plasma membrane, implying a local increase in Ca2+ concentration ([Ca2+]) at the extracellular face of the cell. The possibility that these external [Ca2+] changes may have specific physiological functions has received little consideration in the past. Here we show that, at physiological ambient [Ca2+], Ca2+ mobilization in one cell produces an extracellular signal that can be detected in nearby cells expressing the extracellular Ca2+-sensing receptor (CaR), a cell-surface receptor for divalent cations with a widespread tissue distribution. The CaR may therefore mediate a universal form of intercellular communication that allows cells to be informed of the Ca2+-signalling status of their neighbours.

Efficacy of psoralen plus ultraviolet A therapy vs. biologics in moderate to severe chronic plaque psoriasis: retrospective data analysis of a patient registry.

BACKGROUND: Few studies have directly compared the clinical efficacy of psoralen plus ultraviolet A (PUVA) vs. biologics in the treatment of psoriasis. OBJECTIVES: To compare the clinical efficacy of PUVA and biologic therapies for psoriasis under daily life conditions. METHODS: Data from a psoriasis registry (http://www.psoriasis-therapieregister.at) of 172 adult patients with moderate to severe chronic plaque psoriasis treated between 2003 and 2010 were analysed retrospectively. These patients had received oral PUVA [118 treatment courses including 5-methoxypsoralen (5-MOP; n = 32) and 8-methoxypsoralen (8-MOP; n = 86)] and/or biologic agents [130 treatment courses including adalimumab (n = 18), alefacept (n = 32), efalizumab (n = 17), etanercept (n = 38), infliximab (n = 7) and ustekinumab (n = 18)]. Treatment responses were analysed in terms of Psoriasis Area and Severity Index (PASI) improvement, including complete remission (CR) and reduction of PASI by at least 90% (PASI 90) or 75% (PASI 75), at treatment completion for PUVA (median time 10·3 and 9·2 weeks, for 8-MOP and 5-MOP, respectively) and at week 12 for biologics. RESULTS: Intention-to-treat-as observed CR, PASI 90 and PASI 75 rate was 22%, 69% and 86% for PUVA compared with 6%, 22% and 56% for adalimumab (P = 0·0034 by adapted Wilcoxon test), 3%, 3% and 25% for alefacept (P = 0·000000002), 6%, 6% and 59% for efalizumab (P = 0·000053), 6%, 29% and 39% for etanercept (P = 0·0000086), 29%, 71% and 100% for infliximab (P = 0·36) and 6%, 39% and 67% for ustekinumab (P = 0·028). When applying a more conservative post-hoc modified worst-case scenario analysis, with CR of 15%, PASI 90 of 58% and PASI 75 of 69%, PUVA was superior only to alefacept (P = 0·000013), efalizumab (P = 0·015) and etanercept (P = 0·0037). There were no statistically significant differences in PASI reduction rates between PUVA and infliximab. CONCLUSIONS: Retrospective analysis of registry data revealed that the primary efficacy of PUVA was superior to that of certain biologics. Prospective head-to-head studies of PUVA and biologics are warranted to confirm these observations.

Randomized double-blinded placebo-controlled intra-individual trial on topical treatment with a 1,25-dihydroxyvitamin D3 analogue in polymorphic light eruption.

BACKGROUND: Polymorphic light eruption (PLE) is a very frequent photodermatosis whose pathogenesis may involve resistance to ultraviolet (UV)-induced immune suppression. Similar to UV radiation, calcitriol (1,25-dihydroxyvitamin D3) and its analogues such as calcipotriol have been shown to exhibit immunosuppressive properties. OBJECTIVES: We performed a randomized double-blinded placebo-controlled intraindividual half-body trial (NCT00871052) to investigate the preventive effect of a calcipotriol-containing cream in PLE. METHODS: Thirteen patients with PLE (10 women, three men; mean age 37 years) pretreated their skin on two symmetrically located test fields with calcipotriol or placebo cream twice daily for 7 days before the start of photoprovocation testing with solar-simulated UV radiation. We established a specific PLE test score [AA + SI + 0·4 P (range 0-12), where AA is affected area score (range 0-4), SI is skin infiltration score (range 0-4) and P is pruritus score on a visual analogue scale (range 0-10)] to quantify PLE severity. RESULTS: Photoprovocation led to PLE lesions in 12/13 (92%) patients. As shown by the PLE test score, compared with placebo calcipotrial pretreatment significantly reduced PLE symptoms in average by 32% (95% confidence interval 21-44%; P = 0·0022, exact Wilcoxon signed-rank test) throughout the observation period starting at 48 h until 144 h after the first photoprovocation exposure. At 48, 72 and 144 h calcipotriol pretreatment resulted in a lower PLE test score in 7 (58%), 9 (75%) and 10 (83%) of the 12 cases, respectively. Considering all time points together, calcipotriol diminished the PLE test score in all 12 photoprovocable patients (P = 0·0005; Wilcoxon signed-rank test). CONCLUSIONS: These results suggest a potential therapeutic benefit of topical 1,25-dihydroxyvitamin D3 analogues as prophylactic treatment in patients with PLE.