Intestinal and extraintestinal neoplasms in patients with NTHL1 tumor syndrome: a systematic review.

Germline biallelic pathogenic variants (PVs) in NTHL1 have since 2015 been associated with the autosomal recessive tumor predisposition syndrome: NTHL1 tumor syndrome or NTHL1-associated polyposis. In this systematic review, we aim to systematically investigate the phenotypic and genotypic spectrum of the condition including occurrence of both benign and malignant tumors. The databases PubMed, EMBASE, and Scopus were searched. The search was conducted the 25th of august 2021. We included patients with germline PVs, both heterozygous and homo-/compound heterozygous carriers. Twenty-one papers were selected including 47 patients with biallelic PVs in NTHL1 in 32 families. Twenty-three out of 47 patients (49%) were diagnosed with colorectal cancer (CRC) (mean age: 55, range: 31-73) and 12 out of 22 female patients (55%) were diagnosed with breast cancer (mean age: 49, range: 36-63). Apart from three, all patients who underwent a colonoscopy, had colonic adenomas (93%), and three patients (6%) had duodenal adenomatosis. We also identified 158 heterozygous carriers of germline PVs in NTHL1. Twenty-six out of 68 (38%) heterozygous carriers, who underwent colonoscopy, had colonic polyps or adenomas. Twenty-nine heterozygous carriers (18%) were diagnosed with CRC and 59 (49%) with breast cancer. We observed a high frequency of early onset CRC and breast cancer in patients with NTHL1 tumor syndrome. Subsequently, colorectal, breast, and endometrial cancer screening programs are recommended for NTHL1 biallelic carriers. Trial registry PROSPERO: CRD42021275159.

Process efficiency in relation to enzyme pre-treatment duration in black soldier fly larvae composting.

Black soldier fly larvae (BSFL) composting is a treatment in which biodegradable food waste is converted into animal-feed protein and organic fertiliser. BSFL composting has greatest potential for mixed food waste, but under European Union regulations only plant-based waste is permitted as feed for larvae. Biomass conversion efficiency (BCE) in BSFL composting is lower for plant-based waste than for mixed food waste. One way of improving BCE for plant-based waste is to add enzymes to make the waste more available to the larvae, but enzyme pre-treatment is not commonly applied prior to BSFL composting. Therefore this study examined the impact of enzyme pre-treatment duration on process efficiency in BSFL composting of lettuce-cabbage waste pre-treated with enzymes for 0-4 days. The results showed that total solids (TS) in larvae decreased with longer enzyme pre-treatment. Direct addition of enzymes at the start of BSFL treatment (0 day pre-treatment) resulted in 22% higher BCE on a volatile solids (VS) basis compared with the control, while longer pre-treatment did not improve BCE further. Much of the VS was respired in the 0-day pre-treatment, resulting in lower mass of residues at the end of treatment. Longer pre-treatment increased microbial respiration, suggesting that the microbial community consumed more easily available carbohydrates during the pre-treatment step, which counteracted the purpose of enzyme pre-treatment, i.e. increasing BCE during BSFL composting.

Benefit from extended surveillance interval on colorectal cancer risk in Lynch syndrome.

AIM: Although patients with Lynch syndrome have an increased risk of developing colorectal cancer, surveillance can reduce morbidity and mortality. Whether or not affected individuals benefit from lifetime surveillance depends on individual factors and patient adherence, and these may vary, complicating risk modelling. The aim of this study was to identify individual factors which influence patient adherence to surveillance programmes and whether extended surveillance interval influenced their risk of developing colorectal cancer. METHOD: Demographics and survival data were obtained from patients (n = 1223) with Lynch syndrome, identified by interrogating the Danish Hereditary Non-Polyposis Colorectal Cancer Register. These data were linked to patient surveillance interval data which had been divided into three subsets (< 27 months, adherent to the recommended biennial programme; > 27 months, extended surveillance interval; and no surveillance) to estimate the cumulative risks and hazard ratios (HRs) for colorectal cancer. RESULTS: In all, 147 colorectal cancers (99 first; 48 metachronous) were identified in 1223 patients. Factors associated with adherence to surveillance were female sex, a previous history of cancer and age < 75 years. The cumulative incidence for colorectal cancer was 38% (95% CI 27%-50%) for surveillance intervals < 27 months, 48% (95% CI 29%-67%) for intervals > 27 months and 72% (95% CI 61%-83%) with no surveillance. Adjusted HRs were 0.22 for surveillance intervals < 27 months and 0.32 for surveillance intervals > 27 months. Extended surveillance intervals > 27 months had a non-significant benefit with an HR of 1.51 (95% CI 0.83-2.75) compared to surveillance intervals < 27 months. CONCLUSION: This study demonstrates that adherence to colonoscopic surveillance in Lynch syndrome varies with age, sex and cancer history and demonstrates a consistent benefit from colorectal cancer surveillance, though it might be lower for individuals with extended intervals.

Risk of Synchronous and Metachronous Colorectal Cancer: Population-Based Estimates in Denmark with Focus on Non-Hereditary Cases Diagnosed After Age 50.

BACKGROUND AND AIMS: The risk of synchronous and metachronous colorectal cancer is influenced by heritable and environmental factors. As a basis for comparative studies, we provide population-based estimates of synchronous and metachronous colorectal cancer with a focus on non-heritable cases. MATERIAL AND METHODS: Based on data from national Danish cancer registers, we estimated the proportion of synchronous colorectal cancer and the incidence rates and risks for metachronous colorectal cancer in 28,504 individuals, who developed 577 metachronous colorectal cancer above age 50. RESULTS: Synchronous colorectal cancer was diagnosed in 1.3% of the cases. The risk of metachronous colorectal cancer was associated with sex, tumor location, and age with the strongest influence from the latter. The incidence rate ratios for metachronous colorectal cancer ranged from above 6 in patients below age 65 to <1-3.2 in patients above age 65. The absolute risk of metachronous colorectal cancer was ⩾10% in patients below age 65 and 1.0%-8.0% in patients above age 65. CONCLUSION: Individuals who develop sporadic, non-inherited colorectal cancer above age 50 are at a significantly increased risk of metachronous colorectal cancer with risk estimates that are strongly affected by age. This observation underscores the need for development of targeted surveillance in the most common clinical subset of colorectal cancer.

Socio-economic determinants of vitamin A intake in children under 5 years of age: evidence from Pakistan.

BACKGROUND: Vitamin A deficiency, which is a leading health issue worldwide, is estimated to affect approximately 190 million children globally. The most affected areas are Africa and parts of Southeast Asia. METHODS: The present study examined the use of vitamin A supplementation and the association between socio-demographic factors and vitamin A supplementation in children aged less than 5 years from a cross-sectional demographic survey of Pakistan. Odds ratios were used to express the association between the independent and dependent variables. RESULTS: For 10 906 children, the coverage of vitamin A supplementation was 68.5%, with regional variations of between 8% and 79%. A multiple logistic regression analysis was used on a nationally representative sample of mothers aged 15-49 years. The adjusted results showed that socio-demographic factors such as a maternal age greater than 24 years, living in rural areas and regional variations were positively associated with vitamin A supplementation. CONCLUSIONS: From the results of the present study, we conclude that socio-demographic factors were influential on vitamin A supplementation in children aged less than 5 years. Therefore, national and community-level efforts to support younger mothers in urban areas in the regions with the lowest coverage are needed to increase the acceptance of vitamin A supplementation, aiming to improve the nutritional status of children and decrease inequity in health.

Low grandparental social support combined with low parental socioeconomic status is closely associated with obesity in preschool-aged children: a pilot study.

While the influence of parental socioeconomic status (SES) on children's weight status is well known, the impact of other family-related aspects such as parental and grandparental social support is less understood. This study investigates the importance of parents' SES and social support (functional and structural) for weight status in a clinical sample of preschoolers 4-6 years old with obesity (n = 39, 56% girls; 73% of parents were overweight/obese, 50% were of non-Swedish origin). Linear regression analyses, simple and multiple, were performed on SES and social support with child BMI SDS (body mass index standard deviation score) as the dependent variable. The results show that parents' income and low emotional support from paternal grandparents were significantly associated with more severe obesity. The association between parental income and the child's BMI SDS was stronger among parents who had low emotional support from their own parents. In conclusion, grandparental social support may be protective against childhood obesity.

Maintained superiority of chronotherapeutics vs. exercise in a 20-week randomized follow-up trial in major depression.

OBJECTIVE: To investigate the long-term antidepressant effect of a chronotherapeutic intervention. METHOD: In this randomized controlled trial 75 patients with major depression were allocated to fixed duloxetine and either a chronotherapeutic intervention (wake group) with three initial wake therapies, daily bright light therapy, and sleep time stabilization or to a group using daily exercise. Patients were followed 29 weeks. We report the last 20 weeks, a follow-up phase, where medication could be altered. Patients were assessed every 4 weeks. Remission rates were primary outcome. RESULTS: Patients in the wake group had a statistically significant higher remission rate of 61.9% vs. 37.9% in the exercise group at week 29 (OR = 2.6, CL = 1.3-5.6, P = 0.01). This indicated continued improvement compared with the 9 weeks of treatment response (44.8% vs. 23.4%) with maintenance of the large difference between groups. HAM-D17 endpoint scores were statistically lower in the wake group with endpoint scores of 7.5 (SE = 0.9) vs. 10.1 (SE = 0.9) in the exercise group (difference 2.7, CL = 0.5-4.8, P = 0.02). CONCLUSION: In this clinical study patients continued to improve in the follow-up phase and obtained very high remission rates. This is the first study to show adjunct short-term wake therapy and long-term bright light therapy as an effective and feasible method to attain and maintain remission.

Paediatric ECMO at low-volume paediatric cardiac centres in the Nordic countries.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a life-saving resource-intensive technology for patients with respiratory and/or circulatory failure. We aimed to evaluate outcome data from three Nordic paediatric centres comparing with data from the International Registry of the Extracorporeal Life Support Organization (ELSO) and selected high-volume single-centre studies. METHODS: One-hundred nineteen patients < 19 years from 2002 to 2012 were enrolled. Data on demographics and outcome were collected using a standardised registration form. Outcome data were compared with the ELSO registry and high-volume single-centre studies. RESULTS: Demographics, indications and diagnosis were similar to the ELSO register. Survival after ECMO was similar to outcome data from the ELSO register, apart from paediatric cardiac ECMO, where a significantly better survival to discharge was seen in the Nordic centres (68% vs. 49%; P = 0.03). Comparison with high-volume centres in the period after 2005 demonstrated a significantly better survival after cardiac ECMO in a single high-volume centre study, whereas four studies had significantly lower survival after cardiac ECMO. No significant difference was seen in children receiving respiratory ECMO in the Nordic centres and high-volume centres. CONCLUSIONS: Survival after ECMO in three low-volume Nordic centres demonstrated comparable outcome data with ELSO data and data from high-volume centres. We believe regular quality assurance surveys, as the present study, should be performed in order to maintain excellent therapy within the individual ECMO centres.

Does a magnetic blanket induce changes in muscular blood flow, skin temperature and muscular tension in horses?

REASONS FOR PERFORMING STUDY: Static magnetic blankets are often claimed to induce increases in blood flow, reduce muscle tension and tenderness, and be beneficial in both prevention and treatment of musculoskeletal injuries in horses. However, there are no studies that confirm alleged beneficial effects of magnets on muscles of the back in healthy horses. OBJECTIVES: To investigate whether static magnets sewn into a blanket affect back muscle blood flow, skin temperature, mechanical nociceptive threshold (MNT) and behaviour in healthy horses. STUDY DESIGN: Prospective, randomised, blinded, placebo-controlled crossover study. METHODS: The following outcome measurements of the back of 10 healthy horses were performed; blood flow by photoplethysmography, skin temperature by use of thermistors in conjunction with digital infrared thermography, and MNTs by algometry. The horses' behaviour was filmed during the procedure and scored on an ethogram. Measurements were performed repeatedly for a 30 min baseline period. Thereafter a blanket with active, static magnets (900 gauss) or placebo magnets was placed on the horse and measurements were performed for a 60 min treatment period and a 30 min post treatment period. The study procedure was repeated on the consecutive day, when the horse received the alternative treatment. RESULTS: Blood flow in muscle, skin temperatures, MNTs and behavioural traits did not differ between active and placebo magnetic blankets. Skin temperature increased similarly during both active and placebo blanket treatment. CONCLUSIONS: In healthy horses, magnetic blankets did not induce additional significant effects on muscle blood flow, skin temperature, MNTs and behaviour when compared with nonmagnetic blankets.

Cytomegalovirus prophylaxis in solid organ transplantation.

Human Cytomegalovirus is a commonly identified herpesvirus that establishes a state of latent infection in the majority of the population by adulthood. A coordinated immune response involving both the innate and adaptive immune system prevents active viral replication and disease. Cellular immunity appears particularly important to control of viremia requiring both a CMV-specific CD4+ and CD8+ T cell response. Solid organ transplant recipients are particularly susceptible to CMV related disease due to the immunosuppression necessary to prevent organ rejection, with patients receiving T cell depleting therapies being at highest risk. The deleterious outcomes of CMV in organ transplant recipients result from both direct cytopathic and indirect immune-modulatory effects of CMV viral replication. The recognition of the negative effects of CMV in solid organ transplantation has resulted in the routine prophylaxis of organ recipients with antiviral nucleoside analogues. The appropriate duration of therapy is still controversial although guidelines do exist. The ability to assay an individual immune response to CMV should allow for tailored duration of therapy in the future.

Simultaneously recorded single-exhalation profiles of ethanol, water vapour and CO(2) in humans: impact of pharmacokinetic phases on ethanol airway exchange.

The breath alcohol concentration (BrAC) standardized to the alveolar water vapour concentration has been shown to closely predict the arterial blood alcohol (ethanol) concentration (ABAC). However, a transient increase in the ABAC/BrAC ratio has been noted, when alcohol is absorbed from the gastrointestinal tract (absorption phase) and the ABAC rapidly rises. We analysed the plot of simultaneously recorded alcohol, water vapour and CO(2) against exhaled volume (volumetric expirogram) for respiratory dead space volume (VD), cumulative gas output and phase III slope within one breath to evaluate whether changes in the BrAC profile could explain this variability. Eight healthy subjects performed exhalations through pre-heated non-restrictive mouthpieces and the concentrations were measured by infrared absorption. In the absorption phase, the respiratory VD of alcohol was transiently increased and the exhaled alcohol was displaced to the latter part of the expirogram. In the post-absorption phase, the respiratory VD for alcohol and water vapour was stable and always less than the respiratory VD for CO(2), indicating that the first part of the exhaled alcohol and water originated from the conducting airway. The position of the BrAC profile between water vapour and CO(2) in the post-absorptive phase indicates an interaction within the conducting airway, probably including a deposition of alcohol onto the mucosa during exhalation. We conclude that the increase in the ABAC/BrAC ratio during the absorption phase of alcohol coincides with a transient increase in respiratory VD of alcohol and a delay in the appearance of alcohol in the exhaled air as the exhalation proceeds compared with the post-absorption phase.

Is cartilage sGAG content related to early changes in cartilage disease? Implications for interpretation of dGEMRIC.

OBJECTIVE: This study investigates sulphated glycosaminoglycans (sGAG) content changes in early osteoarthritis (OA), and whether contrast-enhanced magnetic resonance imaging (MRI) of cartilage in vitro may identify early event of OA pathology. METHOD: Osteochondral plugs from patients with hip OA or femoral neck fracture (reference group) were collected and analysed by 1.5 T MRI with ΔR1 as a measure of cartilage contrast concentration. Cartilage hydration, contents of sGAG, cartilage oligomeric matrix protein (COMP), hydroxyproline, denatured collagen, and aggrecan TEGE(392) neoepitope were determined and histological grading was performed. RESULTS: sGAG content correlated to ΔR1, although no difference in either of these parameters was detectable between OA and reference cartilage at 4 h of contrast equilibration. In contrast, biochemical analysis of other cartilage matrix constituents showed distinct alterations typical for early cartilage degradation in OA cartilage and with clear evidence for increased aggrecan turnover. CONCLUSION: In the present in vitro study, cartilage sGAG content could not distinguish between early OA cartilage and reference cartilage. Given, that delayed gadolinium enhanced MRI of cartilage (dGEMRIC) indicates early events in the pathogenesis of OA in vivo, our results from the in vitro studies imply other, additional factors than cartilage sGAG content, e.g., alterations in diffusion or increased supply of contrast agent in the diseased joint. Alternatively, an altered dGEMRIC reflects later stages of OA, when sGAG content decreases. Further investigations are warranted, to understand variations in sGAG content in pathology, an essential background for interpreting dGEMRIC measurements.

Breath alcohol analysis incorporating standardization to water vapour is as precise as blood alcohol analysis.

A novel breath-alcohol analyzer based on the standardization of the breath alcohol concentration (BrAC) to the alveolar-air water vapour concentration has been developed and evaluated. The present study compares results with this particular breath analyzer with arterial blood alcohol concentrations (ABAC), the most relevant quantitative measure of brain alcohol exposure. The precision of analysis of alcohol in arterial blood and breath were determined as well as the agreement between ABAC and BrAC over time post-dosing. Twelve healthy volunteers were administered 0.6g alcohol/kg bodyweight via an orogastric tube. Duplicate breath and arterial blood samples were obtained simultaneously during the absorption, distribution and elimination phases of the alcohol metabolism with particular emphasis on the absorption phase. The precision of the breath analyzer was similar to the determination of blood alcohol concentration by headspace gas chromatography (CV 2.40 vs. 2.38%, p=0.43). The ABAC/BrAC ratio stabilized 30min post-dosing (2089±99; mean±SD). Before this the BrAC tended to underestimate the coexisting ABAC. In conclusion, breath alcohol analysis utilizing standardization of alcohol to water vapour was as precise as blood alcohol analysis, the present "gold standard" method. The BrAC reliably predicted the coexisting ABAC from 30min onwards after the intake of alcohol.

A technique based on laser Doppler flowmetry and photoplethysmography for simultaneously monitoring blood flow at different tissue depths.

The aim of this study was to validate a non-invasive optical probe for simultaneous blood flow measurement at different vascular depths combining three photoplethysmography (PPG) channels and laser Doppler flowmeter (LDF). Wavelengths of the PPG were near-infrared 810 nm with source-to-detector separation of 10 and 25 mm, and green 560 nm with source-to-detector separation of 4 mm. The probe is intended for clinical studies of pressure ulcer aetiology. The probe was placed over the trapezius muscle, and depths from the skin to the trapezius muscle were measured using ultrasound and varied between 3.8 and 23 mm in the 11 subjects included. A provocation procedure inducing a local enhancement of blood flow in the trapezius muscle was used. Blood flows at rest and post-exercise were compared. It can be concluded that this probe is useful as a tool for discriminating between blood flows at different vascular tissue depths. The vascular depths reached for the different channels in this study were at least 23 mm for the near-infrared PPG channel (source-to-detector separation 25 mm), 10-15 mm for the near-infrared PPG channel (separation 10 mm), and shallower than 4 mm for both the green PPG channel (separation 4 mm) and LDF.

A community-based long-term follow up of women undergoing obstetric fistula repair in rural Ethiopia.

OBJECTIVES: To assess urinary and reproductive health and quality of life following surgical repair of obstetric fistula. DESIGN: Follow-up study. SETTING: A newly established fistula clinic (2004) at Gimbie Adventist Hospital, a 71-bedded district general hospital in West Wollega Zone, in rural Western Ethiopia. POPULATION: Thirty-eight women (86%) of 44 who had undergone fistula repair were identified in their community. METHODS: Community-based structured interviews 14-28 months following fistula repair, using a customised questionnaire addressing urinary health, reproductive health and quality of life. MAIN OUTCOME MEASURES: Urinary health at follow up was assessed as completely dry, stress or urge incontinence, or fistula. King's Health Questionnaire was modified and used for the quality-of-life assessment. RESULTS: At follow up, 21 women (57%) were completely dry, 13 (35%) suffered from stress or urge incontinence and three (8%) had a persistent fistula. Surgery improved quality of life and facilitated social reintegration to a level comparable to that experienced before fistula development for both women who were dry and those with residual incontinence (P = 0.001). For women still suffering from fistula no change was seen (P = 0.1). Four women became pregnant following their surgery, among which there was one maternal death, three stillbirths and one re-occurrence of fistula. CONCLUSION: Community-based, long-term follow up after fistula repair succeeded in Western rural Ethiopia. Despite one-third still suffering stress or urge incontinence, the women reported improved quality of life and social reintegration after fistula closure.

Ethnicity, socio-economic status and self-harm in Swedish youth: a national cohort study.

BACKGROUND: Previous studies have shown an elevated risk for self-harm in adolescents from ethnic minorities. However, potential contributions to this risk from socio-economic factors have rarely been addressed. The main aim of this article was to investigate any such effects. METHOD: A national cohort of 1009 157 children born during 1973-1982 was followed prospectively from 1991 to 2002 in Swedish national registers. Multivariate Cox analyses of proportional hazards were used to estimate the relative risk of hospital admission for self-harm. Parental country/region of birth was used as proxy for ethnicity. RESULTS: Youth with two parents born outside Sweden (except those from Southern Europe) had higher age- and gender-adjusted hazard ratios (HRs) of self-harm than the majority population (HR 1.6-2.3). The HRs decreased for all immigrant groups when socio-economic factors were accounted for but remained significantly higher for immigrants from Finland and Western countries and for youth with one Swedish-born and one foreign-born parent. CONCLUSIONS: Socio-economic factors explain much of the variation by parental country of birth of hospital admissions for self-harm in youth in Sweden.

Diagnosis of bacterial kidney disease by detection of Renibacterium salmoninarum by real-time PCR.

Bacterial kidney disease (BKD), caused by Renibacterium salmoninarum (Rs), is a serious threat to salmon in aquaculture as well as to wild populations. We have developed a real-time polymerase chain reaction (PCR) for detection of Rs in kidney samples. The PCR is based on detection of unique parts of the 16S rRNA gene of Rs and DNA equivalent to 1-10 Rs genomes was detected per reaction. No cross-reactivity with other fish pathogenic or related bacteria could be demonstrated. Analysis of individual kidney samples collected from BKD classified populations identified 39.9% of the fish as positive by real-time PCR compared with 28.0% by polyclonal enzyme-linked immunosorbent assay (ELISA). The real-time PCR assay was found to be well suited for complementary use with ELISA for diagnosis of BKD, with the ability to detect clinical as well as covert Rs infections. The infection level determined by the polyclonal ELISA and by real-time PCR was significantly correlated.

Measurement of surgical stress in anaesthetized children.

BACKGROUND: The surgical stress index (SSI), derived from a combination of heart rate (HR) and photoplethysmographic amplitude (PPGA) time series, is a novel method for continuous monitoring of intraoperative stress and has been validated in adults. The applicability of SSI and its constituents to monitoring children has not been previously evaluated. METHODS: In this controlled trial, 22 anaesthetized patients, aged 4-17 yr, undergoing strabismus surgery were randomized into two groups, Group LL and Group BSS. Patients in Group LL received topical conjunctival anaesthesia with a 1:1 mixture of lidocaine 2% and levobupivacaine 0.75%, and patients in Group BSS received balanced salt solution. RESULTS: Endotracheal intubation (n=22) increased median (range) SSI from 39.2 (22.6-55.6) to 53.6 (35.8-63.3) (P<0.001), decreased PPGA from 5.62 (2.79-9.69) to 5.27 (2.59-7.54)% (P=0.001), and increased the difference of response entropy (RE) and state entropy (SE) of frontal biopotentials (RE-SE) from 3.1 (0.06-9.1) to 5.7 (0.6-9.4) (P=0.01). Conventional haemodynamic variables also increased, median (range) HR from 72.9 (56.7-113.8) to 84.2 (60.4-124.8) beats min(-1) (P<0.001), and systolic non-invasive arterial pressure (S-NIBP) from 87 (78-143) to 103 (79-125) (P=0.007). When 3 min baseline before surgery was compared with 12 min of surgery, median (range) SSI increased from 43.3 (31.2-58.0) to 49.9 (39.3-57.2) (P=0.042) vs from 46.6 (26.8-57.8) to 52.1 (31.7-60.1) (P=0.024) and PPGA decreased from 6.60 (3.10-8.24) to 5.80 (3.03-7.65)% (P<0.001) vs from 5.51 (3.25-9.84) to 5.06 (3.08-8.99)% (P=0.042), in Groups LL and BSS, respectively, but SSI or other indicators did not differ significantly between the groups. CONCLUSIONS: SSI, PPGA, HR, NIBP, RE, and RE-SE detect autonomic responses to nociceptive stimuli in anaesthetized children undergoing strabismus surgery.

Repetitive transcranial magnetic stimulation (rTMS) in combination with escitalopram in patients with treatment-resistant major depression: a double-blind, randomised, sham-controlled trial.

BACKGROUND: The role of high-frequency rTMS over the left cortex as an add-on strategy in the treatment of major depression is still uncertain even in patients resistant to pharmacotherapy. We had planned a large sham TMS controlled study in the acute phase with a placebo-controlled relapse-prevention phase with escitalopram. However, because a recent meta-analysis showed only a small effect size of rTMS over sham TMS in the acute treatment phase of depressed patients, we decided to make an interim analysis. METHOD: In patients with medication-resistant major depression we administered in a randomised trial 15 sessions of sham-controlled rTMS over three weeks in combination with 20 mg escitalopram daily. After the last rTMS, the patients were followed for another 9 weeks on 20 mg escitalopram daily. The antidepressant effect was measured by the HAM-D(6) as primary outcome scale. RESULTS: A total of 45 patients with complete data were randomised so that 23 patients received sham TMS and 22 patients received active, high-frequency rTMS over the left cortex. Over the 3 weeks, the active rTMS treatment was superior to sham TMS with effect sizes on the HAM-D(6) above 0.70, which indicates not only a statistically but also a clinically significant effect. The patients had typically been through two failed antidepressant treatment attempts with non-tricyclics before inclusion in the study. Both the rTMS and escitalopram were well-tolerated. CONCLUSION: High-frequency rTMS over the left cortex is an add-on strategy of clinical significance in combination with escitalopram in patients with major depression resistant to non-tricyclic antidepressants.

Genetic analysis of insect bite hypersensitivity (summer eczema) in Icelandic horses.

There is a lack of knowledge about the genetic background of eczema due to insect bite hypersensitivity, also called summer eczema, in horses. The condition is known in several horse breeds and countries and it causes reduced welfare of the horse and economic losses to the owner. The aim of this study was to estimate genetic parameters for summer eczema in Swedish-born Icelandic horses. A questionnaire was sent to owners of horses sired by stallions with more than 50 offspring born in Sweden between 1991 and 2001. Variance components of summer eczema classified as healthy, mild, moderate or severe were estimated using the threshold methodology with sire models. In addition, summer eczema was analysed as a binary trait (healthy v. affected). The analyses included 1250 horses sired by 33 stallions. The prevalence of summer eczema was 8%, with a range of 0% to 30% in different paternal half-sib groups. Offspring of dams suffering from eczema had a higher risk of developing eczema. The heritability for severity of summer eczema was estimated at 0.3 (s.d. < 0.2) with a threshold sire model. In contrast to the age of the horse, different geographic areas and gender were significantly associated with severity of the eczema. We conclude that genetic selection could decrease the prevalence of summer eczema among Swedish-born Icelandic horses. The amount and quality of data are, however, crucial for the possibility to introduce a genetic evaluation of summer eczema. The symptoms should be classified in several classes according to severity, and this classification could be made by the horse owner.