Genome-wide association analysis for susceptibility to infection by Mycobacterium avium ssp. paratuberculosis in US Holsteins.

Paratuberculosis, or Johne's disease, is a chronic, granulomatous, gastrointestinal tract disease of cattle and other ruminants caused by the bacterium Mycobacterium avium subspecies paratuberculosis (MAP). Control of Johne's disease is based on programs of testing and culling animals positive for infection with MAP and concurrently modifying management to reduce the likelihood of infection. The current study was motivated by the hypothesis that genetic variation in host susceptibility to MAP infection can be dissected and quantifiable associations with genetic markers identified. Two separate GWAS analyses were conducted, the first using 897 genotyped Holstein artificial insemination sires with phenotypes derived from incidence of MAP infection among daughters based on milk ELISA testing records. The second GWAS analysis was a case-control design using US Holstein cows phenotyped for MAP infection by serum ELISA or fecal culture tests. Cases included cows positive for either serum ELISA, fecal culture, or both. Controls consisted of animals negative for all tests conducted. A total of 376 samples (70 cases and 306 controls) from a University of Minnesota Johne's management demonstration project and 184 samples (76 cases and 108 controls) from a Michigan State University study were used. Medium-density (sires) and high-density (cows) genotype data were imputed to full genome sequence for the analyses. Marker-trait associations were analyzed using the single-step (ss)GWAS procedure implemented in the BLUPF90 suite of programs. Evidence of significant genomic contributions for susceptibility to MAP infection were observed on multiple chromosomes. Results were combined across studies in a meta-analysis, and increased support for genomic regions on BTA7 and BTA21 were observed. Gene set enrichment analysis suggested pathways for antigen processing and presentation, antimicrobial peptides and natural killer cell-mediated cytotoxicity are relevant to variation in host susceptibility to MAP infection, among others. Genomic prediction was evaluated using a 5-fold cross-validation, and moderate correlations were observed between genomic breeding value predictions and daughter averages (∼0.43 to 0.53) for MAP infection in testing data sets. These results suggest that genomic selection against susceptibility to MAP infection is feasible in Holstein cattle.

The role of competition on invader colonization along stress gradients in the Fuegian steppe.

Competition exerted by native plant communities is an important component of biotic resistance against the spread and impact of non-indigenous plant species in novel habitats. However, how the role of biotic resistance varies along environmental gradients to delay invasions is less clear. We conducted two field experiments to determine how competition from native communities affects colonization of a recognized invader of grasslands, Hieracium pilosella L., in the Fuegian steppe along different environmental gradients at regional and landscape scale. We assessed the role of competition on invader survival and growth along a climate gradient at regional scale (4.7-6.6 °C and 270-450 mm year-1), and across four major plant communities (i.e. meadows, grasslands, scrublands, and heathlands) along a topographic catena. At regional scale, the climate gradient showed a 33% reduction in H. pilosella survival at the coldest and wettest extreme, while reduced its biomass in 41% at the warmest and driest site, in the opposite extreme of the gradient. Competition caused a 34% decrease of the invader biomass, similarly along the climate gradient. At landscape scale, the topographic gradient had a stronger effect on invader survival reaching a 67% reduction in lowland meadows due to flooding events, while competition reduced in 29-39% the invader biomass only in grasslands or scrublands with negligible effects on low-resource heathlands. These results suggest that biotic resistance plays a significant and similar role along the climate gradient to delay invasion at regional scale, but at landscape scale is only determinant for rich-resource communities in absence of abiotic stresses.

The role of subchondral bone, and its histomorphology, on the dynamic viscoelasticity of cartilage, bone and osteochondral cores.

OBJECTIVE: Viscoelastic properties of articular cartilage have been characterised at physiological frequencies. However, studies investigating the interaction between cartilage and subchondral bone and the influence of underlying bone histomorphometry on the viscoelasticity of cartilage are lacking. METHOD: Dynamic Mechanical Analysis (DMA) has been used to quantify the dynamic viscoelasticity of bovine tibial plateau osteochondral cores, over a frequency sweep from 1 to 88 Hz. Specimens (approximately aged between 18 and 30 months) were neither osteoarthritic nor otherwise compromised. A maximum nominal stress of 1.7 MPa was induced. Viscoelastic properties of cores have been compared with that of its components (cartilage and bone) in terms of the elastic and viscous components of both structural stiffness and material modulus. Micro-computed tomography scans were used to quantify the histomorphological properties of the subchondral bone. RESULTS: Opposing frequency-dependent loss stiffness, and modulus, trends were witnessed for osteochondral tissues: for cartilage it increased logarithmically (P < 0.05); for bone it decreased logarithmically (P < 0.05). The storage stiffness of osteochondral cores was logarithmically frequency-dependent (P < 0.05), however, the loss stiffness was typically frequency-independent (P > 0.05). A linear relationship between the subchondral bone plate (SBP) thickness and cartilage thickness (P < 0.001) was identified. Cartilage loss modulus was linearly correlated to bone mineral density (BMD) (P < 0.05) and bone volume (P < 0.05). CONCLUSION: The relationship between the subchondral bone histomorphometry and cartilage viscoelasticity (namely loss modulus) and thickness, have implications for the initiation and progression of osteoarthritis (OA) through an altered ability of cartilage to dissipate energy.

Radical fluoroalkylation reactions of (hetero)arenes and sulfides under red light photocatalysis.

Fluoroalkylation reactions of (hetero)aromatics have been accomplished through the low-power illumination from red LEDs (λmax = 635 nm) of commercially available perfluoroalkyl iodides RF-I and phthalocyanine zinc salt as photocatalyst in MeCN : DMF solvent mixture. This methodology has been extended to the perfluorobutylation of sulfides. As far as we are concerned, this is the first report on a perfluoroalkylation reaction of (hetero)aromatics and sulfides under red-light photocatalysis.

A Fungal Immunotherapeutic Vaccine (NDV-3A) for Treatment of Recurrent Vulvovaginal Candidiasis-A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Recurrent vulvovaginal candidiasis (RVVC) is a problematic form of mucosal Candida infection, characterized by repeated episodes per year. Candida albicans is the most common cause of RVVC. Currently, there are no immunotherapeutic treatments for RVVC. Methods: This exploratory randomized, double-blind, placebo-controlled trial evaluated an immunotherapeutic vaccine (NDV-3A) containing a recombinant C. albicans adhesin/invasin protein for prevention of RVVC. Results: The study in 188 women with RVVC (n = 178 evaluable) showed that 1 intramuscular dose of NDV-3A was safe and generated rapid and robust B- and T-cell immune responses. Post hoc exploratory analyses revealed a statistically significant increase in the percentage of symptom-free patients at 12 months after vaccination (42% vaccinated vs 22% placebo; P = .03) and a doubling in median time to first symptomatic episode (210 days vaccinated vs 105 days placebo) for the subset of patients aged <40 years (n = 137). The analysis of evaluable patients, which combined patients aged <40 years (77%) and ≥40 years (23%), trended toward a positive impact of NDV-3A versus placebo (P = .099). Conclusions: In this unprecedented study of the effectiveness of a fungal vaccine in humans, NDV-3A administered to women with RVVC was safe and highly immunogenic and reduced the frequency of symptomatic episodes of vulvovaginal candidiasis for up to 12 months in women aged <40 years. These results support further development of NDV-3A vaccine and provide guidance for meaningful clinical endpoints for immunotherapeutic management of RVVC. Clinical Trials Registration: NCT01926028.

The British Services Dhaulagiri Medical Research Expedition 2016: a unique military and civilian research collaboration.

INTRODUCTION: High-altitude environments lead to a significant physiological challenge and disease processes which can be life threatening; operational effectiveness at high altitude can be severely compromised. The UK military research is investigating ways of mitigating the physiological effects of high altitude. METHODS: The British Service Dhaulagiri Research Expedition took place from March to May 2016, and the military personnel were invited to consent to a variety of study protocols investigating adaptation to high altitudes and diagnosis of high-altitude illness. The studies took place in remote and austere environments at altitudes of up to 7500 m. RESULTS: This paper gives an overview of the individual research protocols investigated, the execution of the expedition and the challenges involved. 129 servicemen and women were involved at altitudes of up to 7500 m; 8 research protocols were investigated. CONCLUSIONS: The outputs from these studies will help to individualise the acclimatisation process and inform strategies for pre-acclimatisation should troops ever need to deploy at high altitude at short notice.

Concurrent beneficial (vitamin D production) and hazardous (cutaneous DNA damage) impact of repeated low-level summer sunlight exposures.

BACKGROUND: The concurrent impact of repeated low-level summer sunlight exposures on vitamin D production and cutaneous DNA damage, potentially leading to mutagenesis and skin cancer, is unknown. OBJECTIVES: This is an experimental study (i) to determine the dual impact of repeated low-level sunlight exposures on vitamin D status and DNA damage/repair (via both skin and urinary biomarkers) in light-skinned adults; and (ii) to compare outcomes following the same exposures in brown-skinned adults. METHODS: Ten white (phototype II) and six South Asian volunteers (phototype V), aged 23-59 years, received 6 weeks' simulated summer sunlight exposures (95% ultraviolet A/5% ultraviolet B, 1·3 standard erythemal doses three times weekly) wearing summer clothing exposing ~35% body surface area. Assessments made were circulating 25-hydroxyvitamin D [25(OH)D], immunohistochemistry for cyclobutane pyrimidine dimer (CPD)-positive nuclei and urinary biomarkers of direct and oxidative (8-oxo-deoxyguanosine) DNA damage. RESULTS: Serum 25(OH)D rose from mean 36·5 ± 13·0 to 54·3 ± 10·5 nmol L-1 (14·6 ± 5·2 to 21·7 ± 4·2 ng mL-1 ) in phototype II vs. 17·2 ± 6·3 to 25·5 ± 9·5 nmol L-1 (6·9 ± 2·5 to 10·2 ± 3·8 ng mL-1 ) in phototype V (P < 0·05). Phototype II skin showed CPD-positive nuclei immediately postcourse, mean 44% (range 27-84) cleared after 24 h, contrasting with minimal DNA damage and full clearance in phototype V (P < 0·001). The findings did not differ from those following single ultraviolet radiation (UVR) exposure. Urinary CPDs remained below the detection threshold in both groups; 8-oxo-deoxyguanosine was higher in phototype II than V (P = 0·002), but was unaffected by UVR. CONCLUSIONS: Low-dose summer sunlight exposures confer vitamin D sufficiency in light-skinned people concurrently with low-level, nonaccumulating DNA damage. The same exposures produce minimal DNA damage but less vitamin D in brown-skinned people. This informs tailoring of sun-exposure policies.

Anaphylaxis and ethnicity: higher incidence in British South Asians.

BACKGROUND: The incidence of anaphylaxis in South Asians (Indian, Pakistani and Bangladeshi ethnicity) is unknown. Birmingham is a British city with a disproportionately large population of South Asians (22.5%) compared with the rest of the UK (4.9%). The main aims of this study were to determine the incidence and severity of anaphylaxis in this population and to investigate the differences between the South Asian and White populations. METHODS: A retrospective electronic search of emergency department attendances at three hospitals in Birmingham during 2012 was carried out. Wide search terms were used, medical notes were scrutinized, and the World Allergy Organization diagnostic criteria for anaphylaxis were applied. Patients' age, sex, ethnicity and home postal code were collected, reactions were graded by severity, and other relevant details including specialist assessment were extracted. Multivariate analysis was undertaken using 2011 UK census data. RESULTS: Age-, sex- and ethnicity-standardized incidence rate of anaphylaxis was 34.5 per 100 000 person-years. Multivariate logistic regression which controlled for the confounders of age, sex and level of socioeconomic deprivation showed that incidence was higher in the South Asian population (OR 1.48, P = 0.005). Incidence rate in the South Asian population was 58.3 cases per 100 000 person-years compared to 31.5 in the White population. South Asian children were more likely to present with severe anaphylaxis (OR 5.31, P = 0.002). CONCLUSIONS: Incidence of anaphylaxis is significantly higher in British South Asians compared to the white population. British South Asian children are at a greater risk of severe anaphylaxis than White children.

Canadian Cookbooks: Changing Ideas about Cooking and Contamination, 1854-1898.

This study looks to Canadian household manuals, bookended by the watershed publications of Catharine Parr Traill in 1854 and Adelaide Hoodless in 1898, to identify what elements of the rapidly evolving sciences around nutrition, germs, and hygiene made their way to Canadian cooks. In doing so, it also sheds light on some of Canada's early cookbooks, which have to date received deserved bibliographical attention but not yet close analytical scrutiny.

Ambulance handovers: can a dedicated ED nurse solve the delay in ambulance turnaround times?

With ever increasing concern over ambulance handover delays this paper looks at the impact of dedicated A&E nurses for ambulance handovers and the effect it can have on ambulance waiting times. It demonstrates that although such roles can bring about reduced waiting times, it also suggests that using this as a sole method to achieve these targets would require unacceptably low staff utilisation.

Comparison of cryopreserved amniotic membrane and umbilical cord tissue with dehydrated amniotic membrane/chorion tissue.

OBJECTIVE: To evaluate how the different processing methods cryopreservation and dehydration affect the structural integrity and biological composition of key signalling molecules within amniotic membrane and umbilical cord tissues. METHOD: We directly compared cryopreserved amniotic membrane (AM) and umbilical cord (UC) tissues with dehydrated amniotic membrane/chorion (dHACM) tissue using biochemical and functional assays including histological and histochemical staining, BCA, agarose gel electrophoresis, western blot, ELISA, and proliferation and cell death assays. RESULTS: Cryopreservation retains the native architecture of the AM/UC extracellular matrix and maintains the quantity and activity of key biological signals present in fresh AM/UC, including high molecular weight hyaluronic acid, heavy chain-HA complex, and pentraxin 3. In contrast, dehydrated tissues were structurally compromised and almost completely lacked these crucial components. CONCLUSION: The results presented here indicate that cryopreservation better preserves the structural and biological signaling molecules of foetal tissues.

A case of iatrogenic stress? Results of the RCOG August rotation survey.

Although there are a number of studies of patient safety during the August rotation, they often focus on newly qualified doctors. It remains unclear whether negative impacts are due to doctors' inexperience, lack of technical skill or other aspects of rotation. This study used an electronic survey to seek the views of doctors working in obstetrics and gynaecology in the UK. A total of 1,879 responses were received. The August rotation was felt to be a stressful time, with a negative effect on patient care (82%) and safety (73%), lasting up to 1 month (62%). Although reducing services was thought to be helpful, there was strong support for staggering the rotation by grade (80%). This would ensure availability of doctors to cover services during the induction period, which should improve patient care and reduce staff stress. In addition, intensive skills training for junior staff and a supportive culture during the 1st month could optimise the integration and performance of doctors of all grades.

The effect of coronal plane angulation on patient reported outcome measures of operatively treated distal femur fractures: A multi-center prospective evaluation.

OBJECTIVES: The goal of this trial was to determine whether coronal plane angulation affects functional and clinical outcomes after the fixation of distal femur fractures. DESIGN: Multicenter, randomized controlled trial SETTING: 20 academic trauma centers PATIENTS/PARTICIPANTS: 156 patients with distal femur fractures were enrolled. 123 patients were followed 12 months. There was clinical outcome data available for 105 patients at 3 months, 95 patients at 6 months and 81 patients at one year. INTERVENTION: Lateral locked plating or retrograde intramedullary nailing MAIN OUTCOME MEASUREMENTS: Radiographic alignment, functional scoring including SMFA, Bother Index, and EQ-5D. Clinical scoring of walking ability, need for ambulatory support and ability to manage stairs. RESULTS: At 3 months, there was no difference between groups (varus, neutral or valgus) with respect to any of the clinical functional outcome scores measured. At 6 months, compared to those with neutral alignment, patients with varus angulation had a worse Stair Climbing score (4.33 vs. 2.91, p = 0.05). At 12 months, the average patient with neutral or valgus alignment needed less ambulatory support than the average patient in varus. Walking distance ability was no different between the groups at any time point. With respect to the validated patient-based outcome scores, we found no statistical difference in in the SMFA, Bother, or EQ-5D between patients with valgus or varus mal-alignment and those with neutral alignment at any time point (p > 0.05). Regardless of coronal angulation, the SMFA trended towards lower (improved) scores over time, while EQ-5D scores for patients with varus angulation did not improve over time. CONCLUSIONS: Valgus angulation and neutral angulation may be better tolerated in terms of clinical outcomes like stair climbing and need for ambulatory support than varus angulation, though patient reported outcome measures like the SMFA, Bother Index and EQ-5D show no statistical significance. Most patients with distal femur fractures tend to improve during the first year after injury but many remain significantly affected at 12 months post injury.

Use of complementary markers in assessing glycaemic control in people with diabetic kidney disease undergoing iron or erythropoietin treatment.

AIMS: HbA(1c) values are unreliable in patients with diabetes who have chronic kidney disease who receive iron and/or erythropoiesis stimulating agents. The study aimed to evaluate the utility of the complementary glycaemic markers glycated albumin, fructosamine and 1,5 anhydroglucitol in this group of patients. METHODS: A prospective study of patients with Type 2 diabetes and chronic kidney disease stage IIIB/IV undergoing intravenous iron or erythropoiesis-stimulating agent therapy. Glycaemic control was monitored using HbA(1c), seven-point daily glucose thrice weekly, continuous glucose monitoring, glycated albumin, fructosamine and 1,5 anhydroglucitol. RESULTS: Fifteen patients [9 men; median age 72 years (interquartile range 68-74), follow-up period (16.4 ± 3.7 weeks)] received parenteral iron; 15 patients [11 men; 70 years (interquartile range 62-75), (17.3 ± 3.3 weeks)] received erythropoiesis-stimulating agent. HbA(1c) fell following treatment with both iron [57 mmol/mol (7.4%) to 53 mmol/mol (7.0%), P < 0.001] and erythropoiesis-stimulating agent [56 mmol/mol (7.3%) to 49 mmol/mol (6.6%), P = 0.01] despite mean blood glucose remaining unchanged (iron: 9.55 to 9.71 mmol/l, P = 0.07; erythropoiesis-stimulating agent: 8.72 to 8.78 mmol/l, P = 0.89). Unlike HbA1c , the glycated albumin, fructosamine and 1,5 anhydroglucitol levels did not change following iron [glycated albumin (16.8 to 16.3%, P = 0.10); fructosamine (259.5 to 256 µmol/l, P = 0.89); 1,5 anhydroglucitol (54.2 to 50.9 µmol/l, P = 0.89)] or erythropoiesis-stimulating agent [glycated albumin (17.9 to 17.5%, P = 0.29), fructosamine (324.3 to 306.0 µmol/l, P = 0.52), 1,5 anhydroglucitol (58.2 to 46.7 µmol/l, P = 0.35)]. Despite this, HbA(1c) was consistently the marker most closely related to mean blood glucose before and after each treatment (R range 0.7-0.88). CONCLUSIONS: These data indicate that HbA(1c) was statistically most closely related to mean blood glucose, but clinical trends in glycaemia in patients undergoing iron or erythropoiesis-stimulating agent therapy are likely best assessed by including one of these additional glycaemic markers.

Citalopram and cardiac toxicity.

PURPOSE: Citalopram is a selective serotonin reuptake inhibitor (SSRI) antidepressant that is widely used in clinical practice. Recent data have indicated that high therapeutic citalopram doses may cause electrocardiographic abnormalities, and the regulatory authorities have amended its licenced dosage. The present manuscript reviews the available data concerning citalopram and cardiac toxicity. METHODS: Published data concerning the cardiac effects of citalopram were ascertained, and clinical data were considered separately between adverse effects arising from therapeutic use versus toxicity in the setting of intentional overdose. RESULTS: The occurrence of electrocardiographic abnormalities has long been recognised as a complication of acute citalopram overdose; a dose-effect relationship for QT prolongation has been described in a number of large case series, including several cases of torsades de pointes. In contrast, few data indicate the occurrence of QT prolongation and arrhythmia after therapeutic doses, and a dose-effect relationship within the therapeutic range has only recently been established. Citalopram is more likely to cause QT prolongation in patients with metabolic disturbance or pre-existing cardiac disease. CONCLUSIONS: A dose-effect relationship for QT prolongation exists across a broad range of citalopram doses, such that caution must be exercised when prescribing high doses or if there are co-existent risk factors for QT effects. The available data illustrate how clinical toxicity data may offer an earlier signal of cardiac effects than ascertained from conventional pharmacovigilance methods.

Does nausea and vomiting of pregnancy play a role in the association found between maternal caffeine intake and fetal growth restriction?

The aim of this study was to explore the relationships between nausea and vomiting in pregnancy and (a) fetal growth restriction; and (b) maternal caffeine metabolism and fetal growth restriction. A cohort of 2,643 pregnant women, aged 18-45 years, attending two UK maternity units between 8 and 12 weeks gestation, was recruited. A validated tool assessed caffeine intake at different stages of pregnancy and caffeine metabolism was assessed from a caffeine challenge test. Experience of nausea and vomiting of pregnancy was self-reported for each trimester. Adjustment was made for confounders, including salivary cotinine as a biomarker of current smoking status. There were no significant associations between fetal growth restriction and nausea and vomiting in pregnancy, even after adjustment for smoking and alcohol intake. There were no significant differences in the relationship between caffeine intake and fetal growth restriction between those experiencing symptoms of nausea and vomiting and those who did not, for either the first (p = 0.50) or second trimester (p = 0.61) after adjustment for smoking, alcohol intake and caffeine half-life. There were also no significant differences in the relationship between caffeine half-life and fetal growth restriction between those experiencing symptoms of nausea and vomiting and those who did not, for either the first trimester (p = 0.91) or the second trimester (p = 0.45) after adjusting for smoking, alcohol intake and caffeine intake. The results from this study show no evidence that the relationship between maternal caffeine intake and fetal growth restriction is modified by nausea and vomiting in pregnancy.

EffEctiveness of Prophylactic fOam dressings in the prevention of saCral pressure injuries in at-risk hospitalised patients: the EEPOC trial.

BACKGROUND: Prophylactic dressings are increasingly used to prevent pressure injuries in hospitalised patients. However, evidence regarding the effectiveness of these dressings is still emerging. This trial aims to determine the clinical and cost-effectiveness of a prophylactic silicone foam border dressing in preventing sacral pressure injuries in medical-surgical patients. METHODS: This is a multicentre, pragmatic, parallel group, randomised controlled trial. A sample size of 1320 was calculated to have >90% power to detect a 5% difference in the primary outcome at an alpha of 0.05. Adult patients admitted to participating medical-surgical wards are screened for eligibility: ≥18 years, admitted to hospital within the previous 36 h, expected length of stay of ≥24 h, and assessed high risk for hospital-acquired pressure injury. Consenting participants are randomly allocated to either prophylactic silicone foam dressing intervention or usual care without any dressing as the control group via a web-based randomisation service independent of the trial. Patients are enrolled across three Australian hospitals. The primary outcome is the cumulative incidence of patients who develop a sacral pressure injury. Secondary outcomes include the time to sacral pressure injury, incidence of severity (stage) of sacral pressure injury, cost-effectiveness of dressings, and process evaluation. Participant outcomes are assessed daily for up to 14 days by blinded independent outcome assessors using de-identified, digitally modified sacral photographs. Those who develop a sacral pressure injury are followed for an additional 14 days to estimate costs of pressure injury treatment. Analysis of clinical outcomes will be based on intention-to-treat, per-protocol, and sensitivity analyses. DISCUSSION: This trial aims to provide definitive evidence on the effect prophylactic dressings have on the development of hospital-acquired sacral pressure injuries in medical-surgical patients. A parallel economic evaluation of pressure injury prevention and treatment will enable evidence-informed decisions and policy. The inclusion of a process evaluation will help to explain the contextual factors that may have a bearing on trial results including the acceptability of the dressings to patients and staff. The trial commenced 5 March 2020 and has been significantly delayed due to COVID-19. TRIAL REGISTRATION: ANZCTR ACTRN12619000763145. Prospectively registered on 22 May 2019.

Efficacy and tolerability of accelerated-dose low-molecular-weight iron dextran (Cosmofer) in patients with chronic kidney disease.

INTRODUCTION: The Renal NSF advocates correction of anaemia in chronic kidney disease patients. Oral iron is often insufficient, while intravenous supplementation replenishes and maintains iron stores. There is a need to administer high doses of iron in a single rapid infusion to enable efficient costs, effective utilisation of time for patients and staff and optimal use of resources. METHODS: We performed a prospective study of consecutive patients referred for iron dextran (Cosmofer) therapy. This was administered over 2 h 40 min compared with the normal regime of 4-6 h. Blood pressure was recorded throughout administration. Adverse drug reactions were recorded over 2 weeks. Serum ferritin, haemoglobin and estimated glomerular filtration rate were measured at baseline and 3 months. RESULTS: One hundred patients (59 male, mean age 69 years), received a median dose of 1,000 mg Cosmofer in a median time of 2 h 40 min. Mean serum ferritin rose from 178 at baseline to 413 µg/l (p < 0.001). Mean haemoglobin rose by 1.5 g/dl (p < 0.001). There was no decline in estimated glomerular filtration rate after 3 months. No adverse reactions were noted. CONCLUSION: We demonstrated that accelerated administration of iron dextran is safe and effective with no short-term effects on renal function. This resulted in a time saving of approximately 67 hours.

It's not what you hear, it's the way you think about it: appraisals as determinants of affect and behaviour in voice hearers.

BACKGROUND: Previous studies have suggested that beliefs about voices mediate the relationship between actual voice experience and behavioural and affective response. METHOD: We investigated beliefs about voice power (omnipotence), voice intent (malevolence/benevolence) and emotional and behavioural response (resistance/engagement) using the Beliefs About Voices Questionnaire - Revised (BAVQ-R) in 46 voice hearers. Distress was assessed using a wide range of measures: voice-related distress, depression, anxiety, self-esteem and suicidal ideation. Voice topography was assessed using measures of voice severity, frequency and intensity. We predicted that beliefs about voices would show a stronger association with distress than voice topography. RESULTS: Omnipotence had the strongest associations with all measures of distress included in the study whereas malevolence was related to resistance, and benevolence to engagement. As predicted, voice severity, frequency and intensity were not related to distress once beliefs were accounted for. CONCLUSIONS: These results concur with previous findings that beliefs about voice power are key determinants of distress in voice hearers, and should be targeted specifically in psychological interventions.