Long-term, durable, absolute Psoriasis Area and Severity Index and health-related quality of life improvements with risankizumab treatment: a post hoc integrated analysis of patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Risankizumab has demonstrated durable, high rates of efficacy in patients with moderate-to-severe plaque psoriasis as assessed by the achievement of relative Psoriasis Area and Severity Index (PASI) improvement and Dermatology Life Quality Index (DLQI) 0/1. OBJECTIVES: The aim of this post hoc analysis is to assess the achievement of absolute PASI thresholds and related improvements in health-related quality of life (HRQoL) in patients with moderate-to-severe plaque psoriasis treated with (i) risankizumab compared with ustekinumab, and (ii) long-term (>52 weeks to 172 weeks) risankizumab. METHODS: Data from patients randomised to 150 mg risankizumab or 45 or 90 mg ustekinumab in replicate randomised controlled trials UltIMMa-1 and UltIMMa-2 were analysed for the achievement of absolute PASI thresholds PASI ≤ 3, PASI ≤ 1, and PASI = 0, time to achieve these thresholds, and combined PASI and DLQI endpoints. Data from pat ients initially randomised to risankizumab who continued on risankizumab in the open-label extension study LIMMitless were analysed for the achievement of absolute PASI levels, mean DLQI scores, and DLQI 0/1. RESULTS: Significantly greater proportions of patients treated with risankizumab compared with ustekinumab achieved PASI ≤ 3, PASI ≤ 1, and PASI = 0, as well as combined endpoints for absolute PASI and DLQI [(PASI ≤ 3 and DLQI ≤ 5) or (PASI ≤ 1 and DLQI 0/1)]. The median time to first achieve PASI ≤ 3, PASI ≤ 1, and PASI = 0 was significantly lower for risankizumab-treated patients compared with ustekinumab-treated patients. Among patients treated with long-term risankizumab, more than 90% achieved PASI ≤ 3 though week 172 and more than 80% achieved DLQI 0/1. Low absolute PASI scores corresponded with low mean absolute DLQI scores through week 172 of continuous risankizumab treatment. CONCLUSIONS: Risankizumab treatment demonstrated high rates of rapid and durable efficacy as measured by absolute PASI thresholds and improvements in patient HRQoL.

Intermediate to long-term clinical outcomes and survival analysis of the Salto Mobile Bearing total ankle prothesis.

INTRODUCTION: Osteoarthritis of the ankle is a major burden to affected patients. While tibio-talar arthrodesis has been the gold-standard regarding the treatment of osteoarthritis of the ankle joint for many years, at present total ankle arthroplasty (TAA) provides appealing clinical outcomes and is continually gaining popularity. The aim of this study was to evaluate the intermediate- to long-term clinical outcome including the survival rate of Salto Mobile Bearing TAA (Tonier SA, Saint Ismier, France). MATERIAL AND METHODS: In this retrospective study intermediate- to long-term outcomes measures [Ankle Range of Motion (ROM), American Orthopaedic Foot and Ankle Score (AOFAS score) and survival rate] of 171 consecutive TAA were analysed and compared before and after surgery. Revision was defined as secondary surgery with prothesis component removal, while reoperation was defined as a non-revisional secondary surgery involving the ankle. RESULTS: At a mean follow-up (FU) period of 7.2 ± 2.7 years (range 2.0 to 14.1 years) there was a significant improvement in ankle ROM (total ROM improved from 25.0° ± 15.0° to 28.7° ± 11.3°, p = 0.015; plantarflexion improved from 18.4° ± 11.7° to 20.6° ± 8.2°, p = 0.044; dorsiflexion improved from 6.6° ± 5.7° to 8.1° ± 4.9°, p = 0.011). AOFAS score increased significantly by 41 ± 15 points after surgery (43.3 ± 11.1 before and 84.3 ± 12.0 after surgery, p < 0.001). Overall survival rate within the FU was 81.3% (95% CI 75.3% to 87.3%) with any secondary surgery, 89.9% (95% CI 84.1% to 93.6%) with revision and 93.6% (95% CI 89.8% to 97.3%) with reoperation as endpoint. CONCLUSION: This study endorses the previously reported appealing intermediate- to long-term outcomes of the Salto Mobile Bearing TAA. There was a significant increase in ROM and AOFAS score as well as decent implant survival at final FU.

The polygenic risk for obsessive-compulsive disorder is associated with the personality trait harm avoidance.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a complex psychiatric disorder with a substantial genetic contribution. While the specific variants underlying OCD's heritability are still unknown, findings from genome-wide association studies (GWAS) corroborate the importance of common SNPs explaining the phenotypic variance in OCD. Investigating associations between the genetic liability for OCD, as reflected by a polygenic risk score (PRS), and potential endophenotypes of the disorder, such as the personality trait harm avoidance, may aid the understanding of functional pathways from genes to diagnostic phenotypes. METHODS: We derived PRS for OCD at several P-value thresholds based on the latest Psychiatric Genomics Consortium OCD GWAS (2688 cases, 7037 controls) in an independent sample of OCD patients (n = 180), their unaffected first-degree relatives (n = 108) and healthy controls (n = 200). Using linear regression, we tested whether these PRS are associated with the personality trait harm avoidance. RESULTS: Results showed that OCD PRS significantly predicted OCD status, with patients having the highest scores and relatives having intermediate scores. Furthermore, the genetic risk for OCD was associated with harm avoidance across the entire sample, and among OCD patients. As indicated by mediation analyses, harm avoidance mediated the association between the OCD PRS and OCD caseness. These results were observed at multiple P-value thresholds and persisted after the exclusion of patients with a current comorbid major depressive or anxiety disorder. CONCLUSION: Our findings support the polygenic nature of OCD and further validate harm avoidance as a candidate endophenotype and diathesis of OCD.

Harm avoidance and childhood adversities in patients with obsessive-compulsive disorder and their unaffected first-degree relatives.

OBJECTIVE: The etiology of obsessive-compulsive disorder (OCD) is assumed to involve interactions between genetically determined vulnerability factors and significant environmental features. Here, we aim to investigate how the personality trait harm avoidance and the experience of childhood adversities contribute to OCD. METHOD: A total of 169 patients with OCD, 157 healthy comparison subjects, and 57 unaffected first-degree relatives of patients with OCD participated in the study. Harm avoidance was assessed using the Temperament and Character Inventory, and the severity of childhood adversities was measured with the Childhood Trauma Questionnaire. RESULTS: Both patients with OCD and relatives showed elevated levels of harm avoidance compared to controls. Furthermore, patients exhibited significantly higher scores than relatives. This linear pattern was observed throughout all subscales of harm avoidance, and remained stable after controlling for the severity of depressive and obsessive-compulsive symptoms. With regard to childhood adversities, patients with OCD reported higher levels than relatives and controls. CONCLUSION: Our results provide further evidence for a diathesis-stress model of OCD. While patients and unaffected relatives share elevated levels of harm avoidance, supporting the role of harm avoidance as an endophenotype of OCD, a heightened severity of childhood adversity was only observed in patients. The assumed biological underpinnings of these findings are discussed.

Interference of single walled carbon nanotubes (SWCNT) in the measurement of lipid peroxidation in aquatic organisms through TBARS assay.

Nanomaterials (NM) exhibit unique properties due their size and relative area, but the mechanisms and effects in the living organisms are yet to be unfold in their totality. Potential toxicity mechanisms concerning NM as carbon nanotubes include oxidative stress generation. Several fluorimetric and colorimetric methods have been systematically used to measure NM toxicity, and controversial results have been reported. One of the problems can be related to the interference effects induced by NM, leading to artifacts that can lead to misleading conclusions. In present study, it was performed in vitro assays with two aquatic species: the zebrafish Danio rerio and the polychaete Laeonereis acuta to evaluate the potential interference capacity of single-wall carbon nanotubes (SWCNT) in a fluorometric method (TBARS assay) to measure lipid peroxidation. Obtained results indicated that gills and brain of zebrafish presented a lowered fluorescence only at extremely high concentrations (50 and 500mg/L). Determinations in anterior, middle, and posterior body regions of L. acuta showed a quite different pattern: high fluorescence at low SWCNT concentrations (0.5mg/L) and lowering at the highest (500mg/L). To eliminate matrix effect of biological samples, tests employing the standard for TBARS assay, 1,3,3-tetramethoxipropane, were run and the results showed again higher fluorescence values at low concentrations (0.5-5mg SWCNT/L), a technique artifact that could lead to misleading conclusions since higher fluorescence values implicate higher TBARS concentration, implying oxidative stress. Using the colorimetric FOX assay with cumene hydroperoxide as standard presented remarkable better results since no artifacts were observed in the same SWCNT concentration range that employed with the TBARS technique.

Fungal Keratitis: A Six-Year Review at a Tertiary Referral Centre.

Background This review reports the epidemiology, laboratory results, treatment regimens and costs of fungal keratitis at a tertiary referral center in Lucerne, Switzerland. Patients and Methods Culture-proven fungal infections between January 2010 and December 2015 were reviewed retrospectively. Results Seventeen patients with a mean age of 52 years were identified. Contact lens wear was the most important risk factor (n = 11) (65 % of all cases), with filamentous fungi being identified as the most common fungus type (n = 10) (91 % of all cases of contact lens-associated fungal keratitis). All non-contact lens-associated fungal infections (n = 6) (35 % of all cases) were related to Candida spp. Six patients (35 %) were treated on an outpatient basis; 11 cases (65 %) required hospitalisation. Systemic voriconazole was the treatment regimen prescribed most often (n = 12) (71 %), followed by topical natamycin 5 % (n = 11) (65 %). Corneal crosslinking and penetrating keratoplasty were required in 4 cases each (24 %). One case ended up in enucleation (6 %). Average costs per case were EUR 15 952 for hospitalised patients if surgical intervention was required, and EUR 7415 if no intervention was performed. Average costs for outpatients were EUR 7079. In a majority of cases, visual acuity could be improved (n = 9) (53 %) or preserved (n = 2) (12 %). Conclusion Despite the relatively low incidence of culture-proven keratitis (17 cases in 6 years), a clear pattern with regard to risk factors and fungus species was noted. In the absence of a gold standard for the treatment of fungal keratitis, the combination of systemic voriconazole and topical natamycin seems to be one of the most commonly used antifungal treatment regimens. The costs of outpatient versus inpatient non-surgical treatment were approximately the same.

Sex differences in obesity prevalence and cardiometabolic factors among Western Alaska Native people.

BACKGROUND AND AIMS: Obesity is associated with increased risks of cardiovascular disease, type 2 diabetes, and other chronic diseases. Prevalence estimates for metabolic disorders are well documented in many populations, but Alaska Native groups are understudied. The Western Alaska Tribal Collaborative for Health Study combines data from three Alaska Native study cohorts to assess differences in obesity prevalence and associations with cardiometabolic risk factors by sex. METHODS AND RESULTS: Analyses were based upon a sample of 3985 adult Yup'ik and Inupiat participants with a mean age of 40 years. Prevalence of obesity and metabolic risk factors was assessed according to nationally recognized guidelines. Regression analysis was used to evaluate the association between obesity and cardiometabolic risk factors, including lipids, blood pressure and glucose. The prevalence of obesity (BMI ≥ 30) was significantly higher in women (40%) than men (20%). Only 18.6% of men had a waist circumference (WC) > 102 cm, while 58% of women had a WC > 88 cm (p < 0.001). Women had higher mean HDL-C and triglyceride levels compared to men, while systolic and diastolic blood pressure, LDL-C, and glucose means were higher in men than in women. In multivariate analyses, BMI and WC were significantly associated with all of the cardiometabolic risk factors, although these associations were more pronounced in men than women. CONCLUSION: The high prevalence of obesity and central adiposity among AN women is an important public health concern. Differences in associations between obesity and cardiometabolic risk factors by sex warrants further investigation to develop effective intervention programs.

Sugar-feeding behaviour and longevity of European Culicoides biting midges.

Most haematophagous insect vectors can also use sugar as an energy source; thus their sugar-feeding behaviour influences their longevity and blood-feeding rate and hence their vectorial capacity. Scant information is available on the sugar-feeding behaviour of Culicoides Latreille biting midges (Diptera: Ceratopogonidae), which are vectors of bluetongue and Schmallenberg viruses. The longevity of laboratory-reared Culicoides nubeculosus (Meigen) under fluctuating temperatures (16 and 28 °C) and with access to water or water and blood was on average 6.4 days and 8.9 days, respectively, which was around one third of the lifespan of siblings with access to sugar or sugar and blood (22.2 days and 27.1 days, respectively). Access to honeydew significantly increased the midge's longevity, whereas the provision of extrafloral nectaries had no impact. Females with access to sugar produced a significantly higher number of eggs (65.5 ± 5.2) than their starved sisters (45.4 ± 8.4). More than 80% of field-caught female Culicoides from the two most abundant European groups, Obsoletus (n = 2243) and Pulicaris (n = 805), were fructose-positive. Fructose-positivity was high in all physiological stages and no seasonal variability was noted. The high rate of natural sugar feeding of Culicoides offers opportunities for the development of novel control strategies using toxic sugar baits and for the monitoring of vector-borne diseases using sugar-treated FTA (nucleic acid preservation) cards in the field.

Treatment options for demodex blepharitis: patient choice and efficacy.

BACKGROUND: Demodex mites are microscopic parasites that live around hair follicles or sebaceous glands and may cause chronic blepharitis. The aim of this outcome analysis was to assess the efficacy and patient preferences with regard to the currently recommended treatment options. METHODS: All patients with microscopic evidence for Demodex blepharitis were informed about the currently published treatments and instructed about daily lid hygiene. Additional topical treatment options included tea tree oil (TTO) 5%, a cleansing foam containing 0.02% TTO (Naviblef®), and metronidazole 2% ointment. Systemic treatment options included oral ivermectin 6 mg on day 1 and 14 and metronidazole 500 mg twice daily for 10 days. All patients were reviewed after 2 months for symptoms and for a mite count on 10 epilated lashes. RESULTS: Ninety-four of 96 patients with Demodex blepharitis opted for an additional treatment. The mean mite count after 2 months of treatment were 13.3 with 5% TTO (n=6), 12.0 with 0.02% TTO (n=38), 9.4 with metronidazole ointment (n=5), 12.8 with ivermectin (n=27) and 22.0 with oral metronidazole (n=5). CONCLUSION: While there are several published treatment options available, none of these options seem to be clearly effective in Demodex blepharitis.

Specific collaborative group intervention for patients with medically unexplained symptoms in general practice: a cluster randomized controlled trial.

BACKGROUND: Patients with medically unexplained symptoms (MUS) are frequent in primary care and substantially impaired in their quality of life (QoL). Specific training of general practitioners (GPs) alone did not demonstrate sustained improvement at later follow-up in current reviews. We evaluated a collaborative group intervention. METHODS: We conducted a cluster randomized controlled trial. Thirty-five GPs recruited 304 MUS patients (intervention group: 170; control group: 134). All GPs were trained in diagnosis and management of MUS (control condition). Eighteen randomly selected intervention GPs participated in training for a specific collaborative group intervention. They conducted 10 weekly group sessions and 2 booster meetings in their practices, together with a psychosomatic specialist. Six and 12 months after baseline, QoL was assessed with the Short-Form 36. The primary outcome was the physical composite score (PCS), and the secondary outcome was the mental composite score (MCS). RESULTS: At 12 months, intention-to-treat analyses showed a significant between-group effect for the MCS (p = 0.023) but not for the PCS (p = 0.674). This effect was preceded by a significant reduction of somatic symptom severity (15-item somatic symptom severity scale of the Patient Health Questionnaire, PHQ-15) at 6 months (p = 0.008) that lacked significance at 12 months (p = 0.078). As additional between-group effects at 12 months, per-protocol analyses showed less health anxiety (Whiteley-7; p = 0.038) and less psychosocial distress (PHQ; p = 0.024); GP visits were significantly (p = 0.042) reduced in the intervention group. CONCLUSIONS: Compared to pure GP training, collaborative group intervention achieved a progressive, clinically meaningful improvement in mental but not physical QoL. It could bridge gaps between general practice and mental health care.

Evaluation of matrix-assisted laser desorption/ionization time of flight mass spectrometry for the identification of ceratopogonid and culicid larvae.

Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) was evaluated for the rapid identification of ceratopogonid larvae. Optimal sample preparation as evaluated with laboratory-reared biting midges Culicoides nubeculosus was the homogenization of gut-less larvae in 10% formic acid, and analysis of 0.2 mg/ml crude protein homogenate mixed with SA matrix at a ratio of 1:1.5. Using 5 larvae each of 4 ceratopogonid species (C. nubeculosus, C. obsoletus, C. decor, and Dasyhelea sp.) and of 2 culicid species (Aedes aegypti, Ae. japonicus), biomarker mass sets between 27 and 33 masses were determined. In a validation study, 67 larvae belonging to the target species were correctly identified by automated database-based identification (91%) or manual full comparison (9%). Four specimens of non-target species did not yield identification. As anticipated for holometabolous insects, the biomarker mass sets of adults cannot be used for the identification of larvae, and vice versa, because they share only very few similar masses as shown for C. nubeculosus, C. obsoletus, and Ae. japonicus. Thus, protein profiling by MALDI-TOF as a quick, inexpensive and accurate alternative tool is applicable to identify insect larvae of vector species collected in the field.

Treatment of traumatic corneal abrasions: a three-arm, prospective, randomized study.

PURPOSE: To compare three different treatment modalities for traumatic corneal abrasions. METHODS: We conducted a prospective, randomized, masked, three-arm clinical study of patients presenting with superficial corneal foreign bodies. Treatment modalities were: (1) pressure patching with ofloxacin ointment (patch group, PG, n = 18), (2) therapeutic contact lens with ofloxacin eye drops (contact lens group, CLG, n = 20) and (3) ofloxacin ointment alone (ointment group, OG, n = 28). Primary outcome measure was the difference of the mean corneal abrasion area between the three groups at 3 different time points (baseline, day 1 and day 7). RESULTS: A total of 66 patients were included in the study over a period of 2 years. Mean initial corneal abrasion area was 3.6 ± 3.4 mm² in the PG, 4.2 ± 4.0 mm² in the CLG and 3.7 ± 3.1 mm² in the OG (p = 0.875). Differences in corneal abrasion area at any time point were not statistically significant (abrasion area decrease from presentation to day 1 was 3.4 ± 3.3 mm² in the PG, 4.1 ± 4.0 mm² in the CLG and 3.5 ± 3.1 mm² in the OG, p = 0.789). The epithelium was healed in all patients at day 7. CONCLUSIONS: Treating traumatic corneal abrasions by pressure patching, a bandage contact lens or ointment alone was equal in reducing the abrasion area or reducing pain. According to our results the treatment of choice for traumatic abrasions may be adapted to the needs and preferences of the patient.

Central corneal regularization--optimization of uncorrected visual acuity in keratoconus patients.

BACKGROUND: Combined excimer laser correction and corneal cross-linking is a promising concept in treating keratoconus patients. Central corneal regularization represents advanced topography-guided custom ablation for ectatic corneas, aiming at correcting irregular astigmatism and at increasing the optical regularity of the corneal surface. PATIENTS AND METHODS: In a prospective single centre study, 10 keratoconus patients underwent combined treatment with corneal cross-linking and central corneal regularization by an iRES-Laser. Uncorrected visual acuity at 1 and 3 months postoperatively represented the primary endpoint. RESULTS: Mean preoperative uncorrected decimal visual acuity was 0.15 (± 0.28 standard deviation). Mean postoperative visual acuity was 0.28 (± 0.47) at one month and 0.24 (± 0.25) at three months, respectively. CONCLUSIONS: Combined corneal cross-linking and central corneal regularization treatment has the potential to achieve a clinically significant improvement of uncorrected visual acuity.

A fluorophotometric comparison of anterior chamber riboflavin delivery via corneal application and fornix instillation.

INTRODUCTION AND OBJECTIVES: We investigated whether riboflavin self-administration by patients could be a feasible option for corneal cross-linking, given the considerable resources required to impregnate the cornea with riboflavin. We analysed whether administering riboflavin in the inferior fornix (the site of self-administration) results in non-inferior riboflavin concentrations as when applied directly on the cornea (the site of administration by medical personnel). PATIENTS AND METHODS: We conducted a prospective study to evaluate riboflavin concentrations at six time-points (baseline, 5, 15, 30, 45 and 60min) in 18 healthy volunteers for each of two application sites: cornea and fornix. Anterior chamber riboflavin (Peschke® TE 0.25%) concentrations were measured by fluorophotometry (Fluorotron™ Master FM-2). RESULTS: For the two application sites cornea and fornix, participants did not differ in terms of age and sex. At baseline, the autofluorescence in the anterior chamber was 16.7ng/mL (SD 5.5) and 14.6ng/mL (SD 4.6) (P=.221). After 30min, anterior chamber fluorescein concentrations had risen to 55.1ng/mL (SD 25.5) and 46.1ng/mL (SD 25.1) (P=.293) without a further relevant increase by 60min. CONCLUSIONS: This study found that applying riboflavin drops in the inferior fornix was non-inferior to applying it directly to the cornea, based on fluorophotometric measurements of anterior chamber riboflavin concentrations. This suggests that self-application of riboflavin is feasible in terms of corneal riboflavin impregnation.

Physical fitness is associated with neural activity during working memory performance in major depressive disorder.

BACKGROUND: Deficits in cognition like working memory (WM) are highly prevalent symptoms related to major depressive disorder (MDD). Neuroimaging studies have described frontoparietal abnormalities in patients with MDD as a basis for these deficits. Based on research in healthy adults, it is hypothesized that increased physical fitness might be a protective factor for these deficits in MDD. However, the relationship between physical fitness and WM-related neural activity and performance has not been tested in MDD, to date. Understanding these associations could inform the development of physical exercise interventions in MDD. METHODS: Within a larger project, 111 (53female) MDD outpatients and 56 (34female) healthy controls performed an n-back task (0-, 1-, 2-, 3-back) during functional Magnetic Resonance Imaging. Physical fitness from a graded exercise test on a cycle ergometer was performed by 106 MDD patients. RESULTS: Patients showed reduced performance particularly at high loads of the n-back WM task and prolonged reaction times at all n-back loads. A whole-brain interaction analysis of group by WM load revealed reduced neural activity in six frontoparietal clusters at medium and high WM loads in MDD patients compared to healthy controls. Analysis of covariance within the MDD sample showed that physical fitness was associated with neural activity in right and left superior parietal lobules. Externally defined Regions of Interest confirmed this analysis. CONCLUSIONS: Results indicate frontoparietal hypoactivity in MDD at high demands, arguing for decreased WM capacity. We demonstrate a parietal fitness correlate which could be used to guide future research on effects of exercise on cognitive functioning in MDD.

Prevalence of diabetes mellitus secondary to pancreatic diseases (type 3c).

BACKGROUND: Diabetes mellitus secondary to pancreatic diseases is a condition seldom thought of in clinical practice. Yet, a high percentage of exocrine pancreatic insufficiency has been reported for the general population and especially for diabetic subjects. Thus, we investigated the prevalence of diabetes mellitus due to pancreatic diseases. METHODS: In this study, we investigated 1868 patients diagnosed with diabetes mellitus who had been admitted to our hospital during the last 24 months. Patient data were diligently studied, and patients were reclassified according to the diabetes classification as proposed by the American Diabetes Association. RESULTS: Among 1868 subjects, 172 patients could be classified as type 3c diabetes mellitus (9.2%). Among these were 135 diagnosed with chronic pancreatitis (78.5%), 12 with hereditary haemochromatosis, 14 with pancreatic cancer and 7 with cystic fibrosis. Thus, diabetes mellitus due to chronic pancreatitis occurred in this collective in 7.2% of all diabetic subjects. Misclassification of these patients was very common. Only 51.2% (88/172) were initially classified correctly. Most type 3 diabetes patients were initially misclassified as type 2 diabetes (69/84). CONCLUSIONS: Diabetes mellitus secondary to pancreatic diseases (especially chronic pancreatitis) seems more common than generally believed with a prevalence of 9.2% among the subjects studied here. Because the awareness of this diabetes type is poor, misclassification is quite frequent. A common problem seems to be the differentiation between type 2 and type 3. Yet, the right classification of diabetes mellitus is important, because there are special therapeutic options and problems in patients with diabetes secondary to pancreatic diseases.

Parity in patients with chronic inflammatory arthritides childless at time of diagnosis.

OBJECTIVE: To assess parity in women with chronic inflammatory arthritides (CIA) childless at time of diagnosis. METHODS: Patients were selected from the Norwegian Disease-Modifying Anti-Rheumatic Drug (NOR-DMARD) registry. Each patient was matched by year of birth with 100 reference women from the Norwegian Population Registry. Data linkage for patients and references with the Medical Birth Registry of Norway (MBRN) identified all offspring until time of linkage (October 2007). Patients and corresponding references childless at the time of diagnosis were included in the analyses. Kaplan-Meier curves visualized the proportion of childless women and were compared by a log rank test. RESULTS: In all, 156 rheumatoid arthritis (RA), 107 other chronic arthritides (OCA), and 75 juvenile idiopathic arthritis (JIA) patients were childless at time of diagnosis. At the time of data linkage, the proportions (%) of childless RA/OCA/JIA patients versus references were 61.5/62.6/57.3 versus 46.9/42.9/41.0, respectively, all differences statistically significant. The log rank test showed lower parity in all diagnostic groups compared with references (p < 0.001 for RA and OCA and p = 0.002 for JIA). No difference in parity was observed between RA and OCA patients, but both diagnostic groups had lower parity than JIA patients (p = 0.001). Disease characteristics were similar between childless and fertile patients. CONCLUSIONS: Reduced parity was observed in all diagnostic groups compared with references. RA and OCA patients had lower parity than JIA patients, indicating that having the disease as a young adult may influence parity more than having the disease in childhood.

Corneal cross-linking as supplementary treatment option in melting keratitis: a case series.

BACKGROUND: Corneal melting represents a serious condition that can result in corneal perforation and loss of vision. Treatment options include topical and systemic immunosuppression, cyanoacrylate gluing, and emergency keratoplasty, depending on the underlying disease and the stage of corneal melt. Recently, corneal cross-linking (CXL) has emerged as an additional treatment option. The present study evaluates whether CXL induces a clinical improvement in melting keratitis not responding to conventional treatment. HISTORY AND SIGNS: Six patients undergoing CXL for corneal melting of variable origin (including bacterial, fungal and Acanthamoeba keratitis) were reviewed retrospectively. THERAPY AND OUTCOME: Treatment parameters included riboflavin application following UV irradiation with a wavelength of 370 nm and an irradiance of 3 mW/cm2 for 30 minutes. Four patients with corneal melting due to contact lens-related infectious keratitis showed healing without any need for further interventions up to date. In two patients, CXL stabilized the melting cornea and facilitated additional surgical procedures. CONCLUSIONS: By stabilizing corneal collagen fibres, CXL seems to represent an effective option to re-establish corneal integrity in the event of pending perforations. In established perforations, CXL facilitates further emergency procedures by stiffening the tissue.

A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer.

BACKGROUND: This trial was designed to prove superiority of irinotecan over etoposide combined with carboplatin in extensive-disease small-cell lung cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive carboplatin area under the curve 5 mg x min/ml either in combination with irinotecan 50 mg/m2 on days 1, 8, and 15 (IP) or etoposide 140 mg/m2 on days 1-3 (EP). Primary end point was progression-free survival (PFS) at 6 months. Secondary end points were overall survival (OS), response rate, and toxicity. RESULTS: Of 226 patients, 216 were eligible. Median PFS was 6.0 months [95% confidence interval (CI) 5.0-7.0] in the IP arm and 6.0 months (95% CI 5.2-6.8) in EP arm (P = 0.07). Median survival was 10.0 months (95% CI 8.4-11.6) and 9.0 months (95% CI 7.6-10.4) in the IP and EP arm (P = 0.06), respectively. Hazard ratios for disease progression and OS were 1.29 (95% CI 0.96-1.73, P = 0.095) and 1.34 (95% CI 0.97-1.85, P = 0.072), respectively. No difference in response rates was observed. Grade 3 and 4 hematologic toxicity favored the IP arm, whereas diarrhea was significantly more frequent in the IP arm. CONCLUSION: This trial failed to show superiority of irinotecan over etoposide in combination with carboplatin.

Effectiveness of switching between TNF inhibitors in ankylosing spondylitis: data from the NOR-DMARD register.

OBJECTIVE: To assess the effectiveness of switching to a second tumour necrosis factor inhibitor (TNFi) in patients with ankylosing spondylitis (AS). METHODS: Data were extracted from an ongoing longitudinal observational multicentre study in Norway. This study included anti-TNF naïve patients with AS starting treatment with a TNFi as well as treatment with a second TNFi in these same patients. Effectiveness data and 2-year drug survival were compared between switchers and non-switchers and within switchers (first and second TNFi). RESULTS: 514 anti-TNF naïve patients with AS were included; 77 patients switched to a second TNFi while 437 patients did not switch. The percentages of non-switchers using etanercept, infliximab or adalimumab were 53%, 32% and 15%, and the percentages of first and second TNFi in the switchers were 42%, 53% and 5% and 40%, 23% and 36%, respectively. The reason for switching was insufficient response (IR) in 30, adverse events (AEs) in 44 and not reported in 3 patients. Baseline disease activity was similar between the groups. Three-month BASDAI 50 and ASAS 40 responses were achieved by 49% and 38% of non-switchers, by 25% and 30% of switchers after the first TNFi and by 28% and 31% after the second TNFi. The 3-month disease activity level was higher for switchers on the second TNFi than for non-switchers. Drug withdrawal rate was higher during the second TNFi among switchers than for non-switchers (p=0.001). No difference was found in the effectiveness of the second TNFi between switchers due to IR and AE. CONCLUSION: This study confirms that switching to a second TNFi can be effective in AS and can be as useful as in rheumatoid arthritis, although overall effectiveness seems to be somewhat lower than in non-switchers.