How can clinicians detect and treat autism early? Methodological trends of technology use in research.

UNLABELLED: We reviewed original research papers that used quantifiable technology to detect early autism spectrum disorder (ASD) and identified 376 studies from 34 countries from 1965 to 2013. Publications have increased significantly since 2000, with most coming from the USA. Electroencephalogram, magnetic resonance imaging and eye tracking were the most frequently used technologies. CONCLUSION: The use of quantifiable technology to detect early ASD has increased in recent decades, but has had limited impact on early detection and treatment. Further scientific developments are anticipated, and we hope that they will increasingly be used in clinical practice for early ASD screening, diagnosis and intervention.

Hypomania spectrum disorders from adolescence to adulthood: a 15-year follow-up of a community sample.

BACKGROUND: There is a lack of scientific knowledge about the broader spectrum of hypomania in adolescence and the course over time. To investigate this, we used longitudinal data spanning from adolescence to age 31 years. METHOD: A community sample of adolescents (N=2300) was screened for depressive symptoms. Adolescents (16-17 years) with a positive screening and matched controls were interviewed with a structured diagnostic interview. A blinded follow-up assessment was conducted 15 years later, with a structured diagnostic interview covering the age span 19-31 years. Questions about treatment and family history were included. RESULTS: Ninety adolescents (16-17 years) with a lifetime hypomania spectrum episode (3.9% of the total sample) were identified: 40 with fullsyndromal, 18 with brief-episode (<4 day), and 32 with subsyndromal (1-2 main symptoms and 1-2 additional symptoms) hypomania. The hypomania symptoms reported by the fullsyndromal and the brief-episode groups were similar, whereas the subsyndromal group per definition reported fewer symptoms. Of the 90 adolescents with a hypomania spectrum episode, 64 (71%) participated in the follow-up interview. Mania in adulthood was reported by 2 (3%), hypomania by an additional 4 (6%), and major depression by 38 (59%). Incidence of mood episodes in adulthood did not differ between the subgroups of hypomania spectrum. LIMITATIONS: 29% of the participants with hypomania spectrum were lost to follow-up. CONCLUSION: The results indicate that only a small proportion of adolescents with hypomania spectrum episodes continue to have (hypo)mania in adulthood. Thus, maintenance or prophylactic treatment does not seem warranted for this group.

Intimate relationships and childbearing after adolescent depression: a population-based 15 year follow-up study.

PURPOSE: Adolescent depression is associated with a range of interpersonal adversities. We hypothesized that depressed adolescents are at subsequent increased risk of problems related to intimate relationships and childbearing in adulthood, and used longitudinal data to examine this. METHOD: A population-based investigation of depression in 16 to 17 year olds was followed up after 15 years, at around the age of 30 years. Comparisons were made between adolescents with depression (n = 361, 78% females) and non-depressed peers (n = 248, 77% females). Data from both national registers and personal interviews were used. RESULTS: At follow-up, the former depressed and non-depressed adolescents had become parents to a similar extent. The former depressed females were more likely than the non-depressed females to report abortion, miscarriage, intimate partner violence and sexually transmitted disease. They also reported a higher number of intimate relationships and were more likely to have divorced and to be registered as single mothers. Depressed females with a comorbid disruptive disorder had a particularly poor outcome. In the depressed females without a disruptive disorder, only those who subsequently had recurrent depressions in adulthood were at increased risk of poor outcome. There was no indication that the formerly depressed males were at increased risk of subsequent problems related to intimate relationships. CONCLUSION: Females with adolescent depression subsequently have problems related to intimate relationships and childbearing. Disruptive disorders and recurrence of depression appear to be instrumental in this association. Attention should be given to intimate relationship problems and sexual and reproductive health issues in young women with depression.

Mental health outcome of long-term and episodic adolescent depression: 15-year follow-up of a community sample.

BACKGROUND: Recent studies have highlighted the unfavourable natural course of chronic/long-term depression. We investigated the adult mental health outcome of adolescent depression, with specific focus on long-term and episodic adolescent major depression (MD). METHODS: A community sample of depressed adolescents and non-depressed peers was followed-up with a structured diagnostic interview after 15 years. The participants (n=382) were divided into five groups depending on their status in adolescence: no depression (n=155); long-term MD (n=91); episodic MD (n=63); dysthymia (n=33); and subthreshold symptoms (n=40). Outcomes (age 19-31) included mood disorders, other mental disorders, suicidality, and treatment for mental disorders. RESULTS: The long-term group overall had a poorer outcome than the non-depressed group, with the episodic group in an intermediate position. The outcome of the dysthymic group was similar to that of the long-term group, while the subsyndromal group did not differ markedly from the non-depressed group. The long-term group was more likely than the episodic group to report adult anxiety disorders, multiple mental disorders, suicide attempts, and treatment; they also seemed to develop more persistent adult depressions, with a higher number of recurrent episodes and longer duration of antidepressant treatment. Even after adjustment for adolescent factors of clinical and etiological importance, the long-term group had a markedly less favourable outcome than the episodic group. LIMITATION: The participation rate at follow-up was 64.6%. CONCLUSION: Longstanding depression in adolescence is a powerful predictor of continued mental health problems in adulthood. It is now important to evaluate if early interventions can alter this severe course.

Twenty-three deaths with gamma-hydroxybutyrate overdose in western Sweden between 2000 and 2007.

BACKGROUND: gamma-Hydroxybutyrate (GHB) is a drug of abuse with a status as being safe. In spite of a reputation of low toxicity, a huge number of deaths associated with this drug have been recorded during recent years in Sweden. It is unclear whether coingestion with other drugs or ethanol causes death in GHB overdoses or whether GHB itself is the main cause of death. OBJECTIVES: The aim of this study was to analyze the cause of death in GHB-related fatalities seen in our region. METHODS: All cases of deaths with GHB during the year 2000-2007 in the region of western Sweden were studied retrospectively. The cases were classified as either GHB poisonings without any, with a minor or a major influence of other drugs on the cause of death. RESULTS: Twenty-three cases were diagnosed as deaths due to GHB overdose. Ninety-one percent coingested other substances. Ninety-one percent of the decedents were male. Age varied between 16 and 46, with the median age at 25 years. Forty-three percent of the cases were classified as GHB poisonings without any or a minor influence of other drugs on the cause of death. Thirty percent also ingested ethanol. Two patients (9%) were only intoxicated with GHB. CONCLUSIONS: Intoxication with GHB carries some mortality. Combining GHB with ethanol does not explain the many deaths in our region, nor do extremely high plasma concentrations of GHB. The intake of opioids increases the toxicity of GHB. The drug itself has such biological activities that an overdose is dangerous and may lead to death.

Subsequent higher education after adolescent depression: a 15-year follow-up register study.

BACKGROUND: Adolescent depression has been shown to have a range of adverse outcomes. We used longitudinal data to investigate subsequent higher education in former depressed adolescents. METHOD: A Swedish population-based investigation of depression in 16-17-year-olds was followed up in national registers 15 years later. Adolescents with depression (n=361, 78% females) were compared to a group of non-depressed peers of the same age (n=248, 77% females). The main outcome was graduation from higher education by age 30. RESULTS: The adolescent with depression were less likely than their non-depressed peers to have graduated from higher education by age 30, both regarding females (27.7% vs. 36.4%, p<.05) and males (12.7% vs. 28.6%, p<.05). After adjustment for early school performance, socioeconomic status and maternal education, the decreased likelihood of subsequent graduation from higher education remained for depressed males (OR, 0.27; 95% CI, 0.08-0.93) but not for depressed females (OR, 0.93; 95% CI, 0.58-1.49). CONCLUSION: Contrary to what previous research has suggested, adolescent depression and its consequences might be particularly destructive to subsequent higher education in males.

A conceptual model for the development of Phytophthora disease in Quercus robur.

Here, a conceptual model is presented for the development of Phytophthora disease in pedunculate oak. The model is presented using the causal loop diagram tool and gives an overview of how various abiotic and biotic factors, such as soil moisture, nutrient availability and mycorrhizal colonization, may affect the reproduction and the infective capacity of soil-borne Phytophthora species, the susceptibility of the host and subsequent disease development. It is suggested that the link between the root damage caused by Phytophthora species and overall tree vitality is in the assimilation and allocation of carbon within the plants. The potential impact of environmental factors on these processes is discussed. The model is presented with reference to scenarios related to variation in soil moisture and nutrient availability. The need for species-specific validation of the model and the implications of the model are discussed.

A slow form of alpha-2-macroglobulin in diseased and healthy dogs.

Alpha-macroglobulins (AMs) function as non-specific protease inhibitors by using a so-called trapping mechanism, which is a compaction of the molecule that can be seen as a "fast" form in native polyacrylamide gel electrophoresis (PAGE). AMs also play a role in the transport and clearance of cytokines and growth factors from the circulation. In the dog, two AMs are known, alpha-1-macroglobulin (A1M) and alpha-2-macroglobulin (A2M). Using agarose and polyacrylamide gel electrophoresis of canine serum or plasma, we detected a cathodal, slow form of A2M. Upon activation with elastase, slow A2M resembled normal A2M in agarose gel electrophoresis, showing decreased negative charge at semi-saturation but not at full saturation with enzyme. In PAGE, however, slow A2M, unlike normal A2M, did not exhibit a "fast" form after short-term incubation with elastase. After incubation overnight, the "fast" form was seen, indicating a retarded reaction. Incubation of slow A2M with ammonium sulphate, a known activator of AMs, resulted in decreased negative charge in agarose gel electrophoresis and no reaction or partial reaction in PAGE. Slow A2M is present in fresh blood samples or may develop from partial alterations within a few days of storage. Moreover, it is sometimes reversible. Our findings may indicate that slow A2M is a result of an instability of the molecule, leading to a conformational change, which affects electrical charge and impairs the ability to develop into the "fast" form upon activation. This may lead to a delayed clearance of protease and inflammatory mediators from the circulation. Slow A2M was predominantly found in diseased dogs, especially in the Labrador retriever.

Polymorphism of the eosinophil cationic protein-gene is related to the expression of allergic symptoms.

BACKGROUND: We have found a polymorphism in the ECP (eosinophil cationic protein)-gene at position 434 according to GenBank accession number NM 002935. This polymorphism would cause the change of the amino acid arginine (base at position 434 is G) at position 97 to threonine (base at position 434 is C). OBJECTIVE: To investigate the prevalence of the ECP-polymorphism and to screen for disease associations. METHODS: DNA of 209 medical students and 76 asthmatic subjects was analysed. The 434 genotype in the ECP-gene was detected by cleavage of the amplified DNA sequence with the restriction enzyme PstI and analysis of the cleaved product by agarose gel electrophoresis. RESULTS: The prevalences of the polymorphism in the student population were 53%, 39% and 8% for the 434GG, the 434GC and the 434CC genotype, respectively, with allele frequencies of 72% (434G) and 28% (434C). Subjects reporting allergy had a higher prevalence of the 434G allele than non-allergic subjects (P = 0.0056). Of the students who were Phadiatop-positive and had allergic symptoms, 79% had the 434GG genotype, whereas the 434GC and 434CC genotypes were present in 82% of those who did not express allergic symptoms (P < 0.001). Among the 76 patients with asthma, patients with allergic asthma had a significantly higher proportion of 434GG compared with patients with non-allergic asthma (P = 0.04). None of the 18 subjects of the two groups with the 434CC genotype had allergy. CONCLUSION: The 434(G > C) polymorphism in the ECP-gene is related to the development of allergic symptoms, suggesting a central role for the ECP molecule in the process.

[Malpractice in connection with radius fractures must be reduced. Clear guidelines for treatment and follow-up are required]. / Antalet felbehandlingar av radiusfraktur måste minskas. Klara riktlinjer för behandling och uppföljning efterlyses.

PSR handles the vast majority of malpractice injuries in Sweden. PSR is a claims handling company which settles claims for malpractice on behalf of the insurance company owned by the Swedish county councils: the County Councils Mutual Insurance Company. A central issue in the law regulating patient injuries in Swedish health care is to define injuries that could have been avoided if a certain therapeutic/diagnostic procedure or a more appropriate method had been utilized. PSR arranged a multiprofessional conference regarding guidelines to decrease the number of malpractice injuries in the treatment of distal radius fractures. Among the most important issues defined were: To improve and standardize diagnostic imaging Patient information Early decision making in surgery and physical/occupational therapy A more well-defined indication for surgery, in which type of trauma, biological age and functional demands are considered in addition to radiographs Less stereotyped thinking in follow-up Controlled randomized trials.

Atraumatic shoulder instability. Discussion of classification and results after capsular imbrication.

This study consists of 27 shoulders in 24 patients whose atraumatic shoulder instability was treated with the imbrication procedure described by Rockwood. Follow-up after 2 years or more showed the following results: 37% excellent, 30% good, 15% fair and 18% poor (Rowe score). No statistically significant differences in the results were observed between the dominant and non-dominant arm, nor in post-operative return to sports activities. Those with voluntary instability had more laxity at follow-up and tended to have poorer results. Those with unidirectional laxity had only good or excellent results and showed no post-operative laxity. We found no other reliable indication of the results of surgery. The difficulties of classifying shoulder instability by such factors as trauma, laxity and direction of instability are discussed. Overall, we consider capsular imbrication to be a good treatment for involuntary atraumatic shoulder instability.

Drug absorption from nifedipine hydrophilic matrix extended-release (ER) tablet-comparison with an osmotic pump tablet and effect of food.

The aim of the present study was to compare the bioavailability of nifedipine when administered as a hydrophilic matrix tablet (ER) and a push-pull osmotic pump tablet (XL) administrated after fasting, and to evaluate the effect of food for the hydrophilic matrix tablet. For this purpose, three separate studies were performed on healthy volunteers (n = 58) including gammascintigraphic monitoring of tablet erosion and localisation in the gastrointestinal tract for ER in one study. Both ER and XL provided almost constant drug delivery over 24 h, after administration under fasting conditions, and bioequivalence was obtained according to 90% confidence intervals of the difference between formulations within 80-125% for Cmax and AUC. Food significantly increased AUC for ER but no significant difference was obtained between ER and XL with food with respect to extent of bioavailability. The rate of absorption was increased to a higher degree for ER than for XL, as indicated by a Cmax which was almost twice as high for ER compared with XL. This finding was shown to be related to an increased tablet-erosion rate for ER, leading to more rapid drug release.

Differences in co-variation of inorganic elements in the bulk and surface of human deciduous enamel: an induction analysis study.

This paper demonstrates a method for determination of co-variation between some inorganic elements in the bulk and surface areas of human tooth enamel. The technique is based on a computerised induction analysis of data obtained by secondary ion mass spectrometry (SIMS). When comparing the present data with an earlier study from our laboratory, it became evident that with only a moderate increase in the amount of data for the induction analysis, the results increased very considerably in reliability and precision. The patterns of co-variation between different elements differed between the bulk- and surface enamel. Only Mg expressed a similar pattern. In the bulk enamel the elements Na and P expressed a high degree of co-variation. Similarly, Mg and C expressed a high degree of co-variation. Mg was an element often found to co-vary with bulk enamel elements. In the enamel surface, F and Cl co-varied. In addition, Cl was an element often found to co-vary with other enamel surface elements.

Effects of in vivo administration of G-CSF on neutrophil and eosinophil adhesion.

The effect in vivo of G-CSF on neutrophil and eosinophil adhesion was studied after subcutaneous administration to six healthy individuals of human recombinant glycosylated G-CSF (lenograstim) (3 micrograms/kg) for 6 consecutive days. Basal adhesion and adhesion to E-selectin. VCAM-1 and ICAM-1 of neutrophil and eosinophil granulocytes were measured selectively. During G-CSF administration neutrophil basal adhesion increased from 7.4 +/- 3.9% (mean +/- SD) to 55.8 +/- 12.9% and 23.2 +/- 4.4%, 4 and 7 d, respectively, after start of the administration. At the same time points eosinophil basal adhesion increased from 7.1 +/- 2.4% to 37.7 +/- 6.1% and 13.1 +/- 5.3%, respectively. When adhesion was measured in the presence of Mn2+, which increases the functional activity of integrins, an even higher increase of neutrophil and eosinophil basal adhesion was noted 4 and 7 d, respectively, after start of G-CSF administration. In parallel with the enhanced basal adhesion neutrophil adhesion to E-selectin and ICAM-1 and eosinophil adhesion to E-selectin. VCAM-1 and ICAM-1 were significantly (P < 0.05) increased after 4 d of G-CSF administration as was neutrophil cell surface expression of CD11b and CD18. In vitro G-CSF induced minimal changes of granulocyte basal adhesion and inhibition of the adhesion to E-selectin. 10 ng/ml TNF alpha significantly increased neutrophil and eosinophil basal adhesion and adhesion to VCAM-1 and ICAM-1. In summary, administration of G-CSF to healthy subjects induced enhanced adhesion of neutrophil and eosinophil granulocytes, probably mediated by an increase of the functional capacity of beta 1- and beta 2-integrins. The induction of increased levels of TNF alpha might be one mechanism behind the in vivo effect of G-CSF administration.

The plasma concentrations of isosorbide 5-mononitrate (5-ISMN) administered in an extended-release form to patients with acute myocardial infarction.

Eighteen patients with acute myocardial infarction (AMI) followed the same extended-release isosorbide 5-mononitrate dosage regimen as was used in the Fourth International Study of Infarct Survival (ISIS-4). Plasma drug concentrations, blood pressure and heart rate were measured over 5 to 7 days following acute and repeated administrations. After the initial 30 mg dose on the first day of infarction, mean +/- standard deviation Cmax was 1237 +/- 284 nmol l-1 with a median tmax of 4 h (range 1 to 10 h). Following the last 60 mg dose, Cmax was 2685 +/- 497 nmol l-1 with a median tmax of 4 h (2 to 7 h). The plasma concentrations of this extended-release 5-ISMN in patients with acute myocardial infarction were similar to those seen in studies with healthy volunteers. However, drug absorption following the acute dose was protracted in some patients, possibly due to the concomitant administration of morphine. The kinetics of 5-ISMN at steady state were similar for all patients, and none showed protracted 5-ISMN absorption.

Decrease in vertebral bone density after hip arthroplasty. A quantitative computed tomography study in 18 arthrosis cases.

We investigated the bone mineral density (BMD) of the lumbar vertebrae L1-3 with quantitative computed tomography (QCT) in 18 patients who had been operated on with hip arthroplasty because of unilateral arthrosis. In an earlier prospective study, we did not find any bone mineral changes in the femur or tibia after hip arthroplasty in spite of a large increase of the thigh muscle mass as a sign of a remobilization after the operation. The median BMD had decreased 5.3-8.4 percent in all the measured vertebrae after 6 months postoperatively. Because of the patients' improved walking ability after the operation, this decrease in cancellous vertebral BMD is interpreted as a sign of a post-traumatic osteopenia.