Search

Aim: The aim of this study is to analyse the potential impact from the financial crisis (onset in 2009) on suicide rates in Denmark. The hypothesis is that the global financial crisis raised unemployment which leads to raising the suicide rate in Denmark and that the impact is most prominent in men. Method: This study used an ecological study design, including register data from 2001 until 2016 on unemployment, suicide, gender and calendar time which was analysed using Poisson regression models and interrupted time series analysis. Results: The correlation between unemployment and suicide rates was positive in the period and statistically significant for all, but at a moderate level. A dichotomised version of time (calendar year) showed a significant reduction in the suicide rate for women (incidence rate ratio 0.87, P=0.002). Interrupted time series analysis showed a significant decreasing trend for the overall suicide rate and for men in the pre-recession period, which in both cases stagnated after the onset of recession in 2009. The difference between the genders’ suicide rate changed significantly at the onset of recession, as the rate for men increased and the rate for women decreased. Discussion: The Danish social welfare model might have prevented social disintegration and suicide among unemployed, and suicide prevention programmes might have prevented deaths among unemployed and mentally ill individuals. Conclusions: We found some indications for gender-specific differences from the impact of the financial crises on the suicide rate. We recommend that men should be specifically targeted for appropriate prevention programmes during periods of economic downturn.

Background The first oral glucagon-like peptide-1 receptor agonist (GLP-1RA) comprises semaglutide co-formulated with the absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC). Oral semaglutide may alter the pharmacokinetics of co-administered drugs via effects of semaglutide or SNAC. Two separate one-sequence crossover trials investigated the effects of oral semaglutide and SNAC on the pharmacokinetics of ethinylestradiol, levonorgestrel, furosemide and rosuvastatin. Methods Healthy, postmenopausal women (n = 25) received once-daily combined ethinylestradiol and levonorgestrel (Trial 1) and healthy male and female subjects (n = 41) received single doses of furosemide and rosuvastatin (Trial 2), either alone, with SNAC alone or with oral semaglutide. Lack of drug–drug interaction was concluded if 90% confidence intervals (CIs) for the ratio of area under the plasma concentration–time curve (AUC) or maximum concentration (Cmax), with/without oral semaglutide, were within a pre-specified interval (0.80–1.25). Results The AUC values of ethinylestradiol and levonorgestrel were not affected by oral semaglutide co-administration (estimated ratios [90% CI] 1.06 [1.01–1.10] and 1.06 [0.97–1.17], respectively); Cmax was not affected. The no-effect criterion was not met for furosemide or rosuvastatin for the AUC (1.28 [1.16–1.42] and 1.41 [1.24–1.60], respectively) or Cmax. SNAC alone did not affect the AUC or Cmax of ethinylestradiol, levonorgestrel or rosuvastatin; the Cmax of furosemide was slightly decreased. Adverse events were similar to those previously observed for GLP-1RAs (both trials). Conclusion Co-administration with oral semaglutide did not affect the pharmacokinetics of ethinylestradiol or levonorgestrel. There was a small increase in exposure of furosemide and rosuvastatin; however, these increases are not expected to be of clinical relevance. Clinical Trial Registration Numbers NCT02845219 and NCT03010475. Supplementary Information The online version contains supplementary material available at (10.1007/s40262-020-00976-x).

OBJECTIVE This trial compared the efficacy and safety of the first oral glucagon-like peptide 1 (GLP-1) receptor agonist, oral semaglutide, as monotherapy with placebo in patients with type 2 diabetes managed by diet and exercise alone. Two estimands addressed two efficacy-related questions: a treatment policy estimand (regardless of trial product discontinuation or rescue medication use) and a trial product estimand (on trial product without rescue medication use) in all randomized patients. RESEARCH DESIGN AND METHODS This was a 26-week, phase 3a, randomized, double-blind, placebo-controlled, parallel-group trial conducted in 93 sites in nine countries. Adults with type 2 diabetes insufficiently controlled with diet and exercise were randomized (1:1:1:1) to once-daily oral semaglutide 3 mg, 7 mg, 14 mg, or placebo. The primary end point was change from baseline to week 26 in HbA1c. The confirmatory secondary end point was change from baseline to week 26 in body weight. RESULTS In the 703 patients randomized (mean age 55 years, 50.8% male, and mean baseline HbA1c 8.0% [64 mmol/mol]), oral semaglutide reduced HbA1c (placebo-adjusted treatment differences at week 26: treatment policy estimand, −0.6% [3 mg], −0.9% [7 mg], and −1.1% [14 mg]; trial product estimand, −0.7% [3 mg], −1.2% [7 mg], and −1.4% [14 mg]; P < 0.001 for all) and body weight (treatment policy, −0.1 kg [3 mg], −0.9 kg [7 mg], and −2.3 kg [14 mg, P < 0.001]; trial product, −0.2 kg [3 mg], −1.0 kg [7 mg, P = 0.01], and −2.6 kg [14 mg, P < 0.001]). Mild-to-moderate transient gastrointestinal events were the most common adverse events with oral semaglutide. Trial product discontinuations occurred in 2.3–7.4% with oral semaglutide and 2.2% with placebo. CONCLUSIONS In patients with type 2 diabetes, oral semaglutide monotherapy demonstrated superior and clinically relevant improvements in HbA1c (all doses) and body weight loss (14 mg dose) versus placebo, with a safety profile consistent with other GLP-1 receptor agonists.

Purpose: Severe mental illness (SMI) may interfere with parental caregiving practices and offspring development. Adhering to preventive well-child visits and maintaining good oral hygiene during early childhood requires parental involvement. Whether these activities are affected by parental SMI is unclear. The purpose of the present study was to determine whether children exposed to parental SMI are at increased risk of non-attendance to preventive well-child visits and vaccinations at age 0–5 years and of child dental caries experience at age 5 years. Furthermore, interactions between maternal psychiatric and sociodemographic variables in relation to an adverse child outcome were assessed. Methods: Data were obtained from national Danish health registers. All children born in Denmark between January 1997 and December 2010 were followed from birth until their 6th birthday. Results: 679,339 children were included in the study (51% male). Of these, 49,059 children (7.8%) had at least one parent with a lifetime SMI diagnosis. Children of parents with SMI had elevated odds of missing well-child visits and vaccinations (OR 1.41; 95% CI 1.39–1.44, p < 0.0001), and of child dental caries (OR 1.58; 95% CI 1.55–1.62, p < 0.0001). In the presence of maternal SMI, low socioeconomic classification and single-mother status added more to the elevated risk than specific maternal diagnosis or timing of last psychiatric contact. Conclusion: Parents with SMI are less compliant with preventive child healthcare activities than parents without SMI. This indicates a need for practical support to these families in order to prevent inequality in health among their offspring.

Severe mental illness (SMI) may interfere with parental caregiving practices and offspring development. Adhering to preventive well-child visits and maintaining good oral hygiene during early childhood requires parental involvement. Whether these activities are affected by parental SMI is unclear. The purpose of the present study was to determine whether children exposed to parental SMI are at increased risk of non-attendance to preventive well-child visits and vaccinations at age 0-5 years and of child dental caries experience at age 5 years. Furthermore, interactions between maternal psychiatric and sociodemographic variables in relation to an adverse child outcome were assessed.Data were obtained from national Danish health registers. All children born in Denmark between January 1997 and December 2010 were followed from birth until their 6th birthday.679,339 children were included in the study (51% male). Of these, 49,059 children (7.8%) had at least one parent with a lifetime SMI diagnosis. Children of parents with SMI had elevated odds of missing well-child visits and vaccinations (OR 1.41; 95% CI 1.39-1.44, p 0.0001), and of child dental caries (OR 1.58; 95% CI 1.55-1.62, p 0.0001). In the presence of maternal SMI, low socioeconomic classification and single-mother status added more to the elevated risk than specific maternal diagnosis or timing of last psychiatric contact.Parents with SMI are less compliant with preventive child healthcare activities than parents without SMI. This indicates a need for practical support to these families in order to prevent inequality in health among their offspring.

BACKGROUND: Oral semaglutide is the first oral formulation of a glucagon-like peptide-1 (GLP-1) receptor agonist developed for the treatment of type 2 diabetes. We aimed to compare the efficacy and safety of flexible dose adjustments of oral semaglutide with sitagliptin 100 mg. METHODS: In this 52-week, multicentre, randomised, open-label, phase 3a trial, we recruited patients with type 2 diabetes from 81 sites in ten countries. Patients were eligible if they were aged 18 years or older (19 years or older in South Korea), had type 2 diabetes (diagnosed ≥90 days before screening), HbA1c of 7·5-9·5% (58-80 mmol/mol), and were inadequately controlled on stable daily doses of one or two oral glucose-lowering drugs (for 90 days or more before screening). Participants were randomly assigned (1:1) by use of an interactive web-response system, stratified by background glucose-lowering medication at screening, to oral semaglutide with flexible dose adjustments to 3, 7, or 14 mg once daily or sitagliptin 100 mg once daily. To approximate treatment individualisation in clinical practice, oral semaglutide dose could be adjusted on the basis of prespecified HbA1c and tolerability criteria. Two efficacy-related estimands were prespecified: treatment policy (regardless of treatment discontinuation or use of rescue medication) and trial product (on treatment and without use of rescue medication) for participants randomly assigned to treatment. The primary endpoint was achievement of HbA1c of less than 7% (53 mmol/mol) at week 52 and the confirmatory secondary efficacy endpoint was change in bodyweight from baseline to week 52. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02849080, and European Clinical Trials Database, EudraCT number 2015-005593-38, and an open-label extension is ongoing. FINDINGS: Between Sept 20, 2016, and Feb 7, 2017, of 804 patients assessed for eligibility, 504 were eligible and randomly assigned to oral semaglutide (n=253) or sitagliptin (n=251). Most participants were male (285 [57%] of 504) with a mean age of 57·4 years (SD 9·9). All participants were given at least one dose of their allocated study drug except for one participant in the sitagliptin group. From a mean baseline HbA1c of 8·3% (SD 0·6%; 67 mmol/mol [SD 6·4]), a greater proportion of participants achieved an HbA1c of less than 7% with oral semaglutide than did with sitagliptin (treatment policy estimand: 58% [134 of 230] vs 25% [60 of 238]; and trial product estimand: 63% [123 of 196] vs 28% [52 of 184]). The odds of achieving an HbA1c of less than 7% was significantly better with oral semaglutide than sitagliptin (treatment policy estimand: odds ratio [OR] 4·40, 95% CI 2·89-6·70, p

Aim: Few population-based, family studies have examined associations between exposure to one vs. two parent(s) with alcohol use disorder (AUD) and the risk of offspring developing substance use disorder (SUD). Moreover, these studies have focused solely on the development of AUD, and not SUD, in offspring. The purpose of this study was to investigate whether exposure to one vs. two parent(s) with AUD increases the risk of offspring developing SUD. Methods: A population-based, cohort study was conducted in which offspring born in Denmark between 1983 and 1989 were followed through national registries until 2011. Register-based data were obtained from the: Psychiatric Central Research Register, National Patient Registry, Civil Registration System, Fertility Database, and Cause of Death Register. Adjusted hazard ratios were calculated using multivariate Cox-regression models.Findings: A total of 398,881 offspring were included in this study. Of these, 3.9 % had at least one parent with AUD. Parental AUD was significantly associated with the development of SUD in offspring. Having one parent with AUD was linked to a 1.44-fold increased risk (95% CL, 1.29 - 1.61), while having two parents with AUD was linked to a 2.29-fold increased risk (95% CI, 1.64 – 3.20). No significant differences were found in relation to either parental or offspring gender.Conclusions: Exposure to parental AUD is linked to an increased risk of offspring developing SUD. This risk is additive for offspring exposed to double parental AUD. The findings have important implications for clinical assessment and intervention strategies, as well as the management of offspring exposed to parental AUD.

Background The pharmacokinetic properties of liraglutide, a glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes mellitus (T2D), have been established in healthy individuals and subjects with T2D. Liraglutide has been under investigation as adjunct treatment to insulin in type 1 diabetes mellitus (T1D). This single-center, double-blind, placebo-controlled, crossover, clinical pharmacology trial is the first to analyze the pharmacokinetic properties of liraglutide as add-on to insulin in T1D. Methods Subjects (18–64 years; body mass index 20.0–28.0 kg/m2; glycated hemoglobin ≤9.5 %) were randomized 1:1:1 to 0.6, 1.2, or 1.8 mg liraglutide/placebo. Each group underwent two 4-week treatment periods (liraglutide then placebo or placebo then liraglutide) separated by a 2- to 3-week washout. Both trial drugs were administered subcutaneously, once daily, as adjunct to insulin. A stepwise hypoglycemic clamp was performed at the end of each treatment period (data reported previously). Pharmacokinetic endpoints were derived from liraglutide concentration–time curves after the final dose and exposure was compared with data from previous trials in healthy volunteers and subjects with T2D. Results The pharmacokinetic properties of liraglutide in T1D were comparable with those observed in healthy volunteers and subjects with T2D. Area under the steady-state concentration–time curve (AUC) and maximum plasma concentration data were consistent with dose proportionality of liraglutide. Comparison of dose-normalized liraglutide AUC suggested that exposure in T1D, when administered with insulin, is comparable with that observed in T2D. Conclusions Liraglutide, administered as adjunct to insulin in subjects with T1D, shows comparable pharmacokinetics to those in subjects with T2D. ClinicalTrials.gov Identifier: NCT01536665.

OBJECTIVE In the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) cardiovascular (CV) outcomes trial (NCT01179048), liraglutide significantly reduced the risk of CV events (by 13%) and hypoglycemia versus placebo. This post hoc analysis examines the associations between hypoglycemia and CV outcomes and death. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes and high risk for CV disease (n = 9,340) were randomized 1:1 to liraglutide or placebo, both in addition to standard treatment, and followed for 3.5–5 years. The primary end point was time to first major adverse cardiovascular event (MACE) (1,302 first events recorded), and secondary end points included incidence of hypoglycemia. We used Cox regression to analyze time to first MACE, CV death, non-CV death, or all-cause death with hypoglycemia as a factor or time-dependent covariate. RESULTS A total of 267 patients experienced severe hypoglycemia (liraglutide n = 114, placebo n = 153; rate ratio 0.69; 95% CI 0.51, 0.93). These patients had longer diabetes duration, higher incidence of heart failure and kidney disease, and used insulin more frequently at baseline than those without severe hypoglycemia. In combined analysis (liraglutide and placebo), patients with severe hypoglycemia were more likely to experience MACE, CV death, and all-cause death, with higher risk shortly after hypoglycemia. The impact of liraglutide on risk of MACE was similar in patients with and without severe hypoglycemia (P-interaction = 0.90). CONCLUSIONS Patients experiencing severe hypoglycemia were at greater risk of CV events and death, particularly shortly after the hypoglycemic episode. While causality remains unclear, reducing hypoglycemia remains an important goal in diabetes management.

Eating disorders (EDs) comprise a variety of symptoms and have a profound impact on everyday life. They are associated with high morbidity and mortality. The objective of this study was to analyse published data on health-related quality of life (HRQoL) in EDs so as to compare the results to general population norm data and to investigate potential differences between ED diagnostic groups. A systematic review of the current literature was conducted using a keyword-based search in PubMed and PsychInfo. The search covered anorexia nervosa (AN), bulimia nervosa (BN), eating disorders not otherwise specified (EDNOS) and binge eating disorder (BED) and used the Medical Outcomes Study Short Form-36 Health Survey (SF-36) as a measure of HRQoL. Of the 102 citations identified, 85 abstracts were reviewed and seven studies were included in the meta-analysis. AN patients were included in five studies (n=227), BN in four studies (n=216), EDNOS in two studies (n=166) and BED in four studies (n=148). We tested for between-study variation and significant differences between the diagnostic groups. The results confirmed a significantly lower level of HRQoL in all EDs compared to a population mean. It was not possible to establish any differences between the diagnostic groups.

Exercise addiction is characterized by excessive exercise patterns with potential negative consequences such as overuse injuries. The aim of this study was to compare eating disorder symptoms, quality of life, personality traits and attachments styles in exercisers with and without indications of exercise addiction. A case-control study with 121 exercisers was conducted. The exercisers were categorized into an addiction group (n=41) or a control group (n=80) on the basis of their responses to the Exercise Addiction Inventory. The participants completed the Eating Disorder Inventory 2, the Short-Form 36, the NEO Personality Inventory Revised and the Adult Attachment Scale. The addiction group scored higher on eating disorder symptoms, especially on perfectionism but not as high as eating disorder populations. The characteristic personality traits in the addiction group were high levels of excitement-seeking and achievement striving whereas scores on straightforwardness and compliance were lower than in the exercise control group. The addiction group reported more bodily pain and injuries. This study supports the hypothesis that exercise addiction is separate to an eating disorder, but shares some of the concerns of body and performance. It is driven by a striving for high goals and excitement which results in pain and injuries from overuse.

BACKGROUND: The optimal rehabilitation program after meniscus repair has not been established. Numerous regimens have been suggested as beneficial for meniscus healing, but no controlled trials exist in the literature.HYPOTHESIS: The purpose of this prospective randomized trial was to investigate outcome with a free or a restricted rehabilitation regimen after isolated meniscus repair. The hypothesis was that free rehabilitation would result in increased failure of meniscus healing.STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 1.METHODS: A total of 60 patients were included in this study within 2 to 3 days after meniscus repair. No patients with concomitant ligament reconstruction or cartilage repair surgery were included. Meniscus repair was performed with the all-inside technique; only vertical meniscus lesions close to the capsule were repaired. Patients were randomized to free (n = 32) or restricted (n = 28) rehabilitation. Free rehabilitation consisted of 2 weeks (range of motion [ROM], 0°-90°, no brace) and touch weightbearing, with unrestricted activity and free ROM allowed thereafter. Restricted rehabilitation consisted of 6 weeks of hinged brace use with a gradual increase ROM to 90° and only touch weightbearing during the 6 weeks. Patients were seen for follow-up at 3 months, 1 year, and 2 years. Those patients with joint line pain at the 3-month follow-up underwent MRI scanning to evaluate meniscus healing; a subsequent arthroscopy was performed for final evaluation meniscus healing if the MRI indicated lack of meniscus healing. At follow-up, the Knee Osteoarthritis Outcome Score (KOOS), Tegner function score, pain assessment, and patient satisfaction were used to evaluate outcomes.RESULTS: Eleven patients were lost to follow-up. Repeat arthroscopy in patients with persistent symptoms demonstrated partial healing or lack of healing in 28% and 36% of patients in the free and the restricted rehabilitation groups, respectively (P = .53, nonsignificant). The KOOS and Tegner function scores were similar between groups at all follow-up times, as was patient satisfaction. Patients who underwent subsequent partial meniscectomy because of meniscus repair failure had lower KOOS score and Tegner function score than did patients without repair failure.CONCLUSION: Free rehabilitation after meniscus repair is safe and does not entail increased failure rates compared with restricted rehabilitation. Subjective and functional outcomes at 1- and 2-year follow-up were not affected by rehabilitation regimen. Clinical outcomes in patients with repair failure who underwent subsequent partial meniscectomy were poorer than in those with healed meniscus repairs. A concern is the 30% overall lack of healing for patients with isolated meniscus lesions repaired with the all-inside technique.

Background and aim: The aim of the study was to identify risk factors for significant changes in emotional and behavioural problem load in a community-based cohort of Danish children aged 9-16 years, the risk factors being seven parental and two child-related adverse life events. Methods: Data on emotional and behavioural problems was obtained from parents filling in the Child Behavior Checklist (CBCL) when the child was 8-9 and again when 15 years old. Data on risk factors was drawn from Danish registers. Analysis used was logistic regression for crude and adjusted change. Results: Parental divorce significantly raised the odds ratio of an increase in emotional and behavioural problems; furthermore, the risk of deterioration in problem behaviour rose significantly with increasing number of adverse life events. By dividing the children into four groups based on the pathway in problem load (increasers, decreasers, high persisters and low persisters), we found that children with a consistently high level of behavioural problems also had the highest number of adverse life events compared with any other group. Conclusions: Family break-up was found to be a significant risk factor. This supports findings in previous studies. The fact that no other risk factor proved to be of significance might be due to lack of power in the study. Children experiencing high levels of adverse life events are at high risk of chronic problem behaviour. Thus these risk factors should be assessed in daily clinical practice.

OBJECTIVE To investigate the efficacy and safety of liraglutide added to capped insulin doses in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS A 26-week, placebo-controlled, double-blind, parallel-group trial enrolling 835 subjects randomized 3:1 receiving once-daily subcutaneous liraglutide (1.8, 1.2, and 0.6 mg) or placebo added to an individually capped total daily dose of insulin. RESULTS Mean baseline glycated hemoglobin (HbA1c) (8.1% [65.0 mmol/mol]) was significantly decreased with liraglutide versus placebo at week 26 (1.8 mg: –0.33% [3.6 mmol/mol]; 1.2 mg: –0.22% [2.4 mmol/mol]; 0.6 mg: –0.23% [2.5 mmol/mol]; placebo: 0.01% [0.1 mmol/mol]). Liraglutide significantly reduced mean body weight (–5.1, –4.0, and –2.5 kg for 1.8, 1.2, and 0.6 mg, respectively) versus placebo (–0.2 kg). Significant reductions in daily insulin dose and increases in quality of life were seen with liraglutide versus placebo. There were higher rates of symptomatic hypoglycemia (21.3 vs. 16.6 events/patient/year; P = 0.03) with liraglutide 1.2 mg vs. placebo and of hyperglycemia with ketosis >1.5 mmol/L with liraglutide 1.8 mg vs. placebo (0.5 vs. 0.1 events/patient/year; P = 0.01). CONCLUSIONS In a broad population of subjects with long-standing type 1 diabetes, liraglutide added to capped insulin reduced HbA1c, body weight, and insulin requirements but with higher rates of hypoglycemia for liraglutide 1.2 mg and hyperglycemia with ketosis for liraglutide 1.8 mg.

OBJECTIVETo investigate whether liraglutide added to treat-to-target insulin improves glycemic control and reduces insulin requirements and body weight in subjects with type 1 diabetes.RESEARCH DESIGN AND METHODSA 52-week, double-blind, treat-to-target trial involving 1,398 adults randomized 3:1 to receive once-daily subcutaneous injections of liraglutide (1.8, 1.2, or 0.6 mg) or placebo added to insulin.RESULTSHbA1c level was reduced 0.34–0.54% (3.7–5.9 mmol/mol) from a mean baseline of 8.2% (66 mmol/mol), and significantly more for liraglutide 1.8 and 1.2 mg compared with placebo (estimated treatment differences [ETDs]: 1.8 mg liraglutide −0.20% [95% CI −0.32; −0.07]; 1.2 mg liraglutide −0.15% [95% CI −0.27; −0.03]; 0.6 mg liraglutide −0.09% [95% CI −0.21; 0.03]). Insulin doses were reduced by the addition of liraglutide 1.8 and 1.2 mg versus placebo (estimated treatment ratios: 1.8 mg liraglutide 0.92 [95% CI 0.88; 0.96]; 1.2 mg liraglutide 0.95 [95% CI 0.91; 0.99]; 0.6 mg liraglutide 1.00 [95% CI 0.96; 1.04]). Mean body weight was significantly reduced in all liraglutide groups compared with placebo ETDs (1.8 mg liraglutide −4.9 kg [95% CI −5.7; −4.2]; 1.2 mg liraglutide −3.6 kg [95% CI −4.3; −2.8]; 0.6 mg liraglutide −2.2 kg [95% CI −2.9; −1.5]). The rate of symptomatic hypoglycemia increased in all liraglutide groups (estimated rate ratios: 1.8 mg liraglutide 1.31 [95% CI 1.07; 1.59]; 1.2 mg liraglutide 1.27 [95% CI 1.03; 1.55]; 0.6 mg liraglutide 1.17 [95% CI 0.97; 1.43]), and hyperglycemia with ketosis increased significantly for liraglutide 1.8 mg only (event rate ratio 2.22 [95% CI 1.13; 4.34]).CONCLUSIONSLiraglutide added to insulin therapy reduced HbA1c levels, total insulin dose, and body weight in a population that was generally representative of subjects with type 1 diabetes, accompanied by increased rates of symptomatic hypoglycemia and hyperglycemia with ketosis, thereby limiting clinical use in this group.

Background: Many patients with psychiatric illnesses have difficulty maintaining medication over time. Many take their medicine irregularly and studies show that it is the most vulnerable patients who have the greatest problems adhering to treatment. Often only 50% are still under medical treatment after 6 months. Aim: In this study we investigated whether text message reminders could improve medicine compliance amongst vulnerable young people with psychiatric disorders who were being treated in the outpatient department for child and adolescent psychiatry and who either are under or were to commence medicinal treatment. Methods: This study was conducted as a randomized controlled trial including all non-acute referrals to an outpatient department for adolescent psychiatry within a group aged 15-20 years starting medical treatment. The patients were followed until the end of their treatment, for a minimum of 3 months. To enhance medicine compliance, text messages were sent daily to one group. No message was sent to the other group. Results: Compliance was not associated with text message intervention in any of the drug interventions. The effect size was calculated to 0.3013, which is low and therefore indicates a weak association between text message and compliance. The power in this study was calculated to 0.3539, which is also low and therefore the likelihood of finding significant association is low. Conclusion: This study does not show increased medicine compliance from the text message intervention group. The conclusion of this study is that it is essential that significant resources are spent preparing and testing a text message strategy. © 2015 Taylor & Francis.

The objective of this study was to determine predictors of repeated suicide attempts in young people, focusing on psychiatric illness. A longitudinal population-based register study of all adolescents born in Denmark between 1984 and 2006 was conducted. Greater numbers of hospitalizations, psychiatric diagnoses, and psychopharmacological medications prescribed to youth before and after the index attempt were risk factors for repeated suicide attempts. Parental diagnoses and drug prescriptions following a child's first suicide attempt moderated the risk of repeated attempts. Psychiatric illness is a strong predictor of repeated suicide attempts in young people, and those with co-morbid diagnoses are at increased risk of repeated suicide attempts. Treatment of psychiatric illness in the parents after their child's first suicide attempt is a potential protective factor.

Purpose This study presents clinical results of a case series of isolated reconstruction of the posterolateral corner (PLC) with a new technique that aims to reconstruct the lateral collateral ligament (LCL), popliteus tendon, and popliteofibular ligament. Methods From 1997 to 2005, 27 patients available for follow-up with isolated posterolateral instability were treated with primary reconstruction of the LCL and PLC. The median age was 28 years, and there were 16 male patients. Of the patients, 26% had remaining instability after anterior or posterior cruciate ligament reconstruction. All underwent reconstruction with a novel technique addressing both the LCL and the PLC by use of hamstring autografts. Follow-up was more than 24 months, and patients were examined by an independent observer using the International Knee Documentation Committee objective measures and subjective Knee Injury and Osteoarthritis Outcome Scores. Results In our series 95% of patients with isolated lateral rotatory instability had rotatory stability after PLC reconstruction. On the basis of International Knee Documentation Committee scoring, 71% were normal or nearly normal. Subjective Knee Injury and Osteoarthritis Outcome Scores were comparable to scores in patients after meniscectomy. One patient had a deep infection, but none had any peroneal nerve injury. Conclusions This case series presents a new method for combined reconstruction of the LCL and the PLC. Despite the extensiveness of procedure, complications were low. The technique restores lateral stability clinically at 2 years' follow-up. Level of Evidence Level IV, therapeutic case series.

Antibodies against double-stranded (ds) DNA were demonstrated by an immunofluorescence technique using Crithidia luciliae kinetoplast as antigen, and by means of the Farr technique. Both techniques were used simultaneously in 172 sera from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), temporal arteritis (TA) and from healthy controls. Comparable results were obtained with the two techniques. SLE patients with active disease had higher titres of IgA antibodies than patients with inactive disease. Of the patients with RA and JRA, 10% had significant titres of dsDNA antibodies. Patients with TA and normal controls had either no dsDNA antibodies in their sera or very low titres without complement-fixing properties.

Background In cases of multiple ligament injury or severe medial collateral ligament (MCL) lesion, nonoperative treatment of the MCL lesion may lead to chronic valgus instability or rotatory instability. Hypothesis In a retrospective case series after isolated and combined MCL reconstructions using a novel MCL reconstruction technique that addresses both the MCL and the posteromedial corner, an acceptable clinical outcome is expected 2 years after MCL reconstruction. Study Design Case series; Level of evidence, 4. Methods From July 2002 to December 2005, 61 patients with grade 3 or 4 medial instability were treated with MCL reconstruction. Median age was 33 years (range, 14–62). Thirteen underwent isolated MCL reconstructions, 34 had combined MCL and anterior cruciate ligament (ACL) reconstruction, and 14 had multiple ligament reconstructions. All patients had reconstruction of the medial collateral and the posteromedial complex using ipsilateral semitendinosus autografts. Fifty patients were available for follow-up more than 24 months postoperatively and were examined by an independent observer using objective International Knee Documentation Committee (IKDC) measures and subjective Knee Injury and Osteoarthritis Outcome Score (KOOS). Results At follow-up, medial stability according to the IKDC score showed 98% normal or nearly normal (grade A or B), and for overall IKDC score, patients improved from 5% with grade A or B preoperatively to 74% with grade A or B at follow-up. There were 91% who were satisfied or very satisfied with the result; 88% would go through surgery again. The KOOS improved primarily for sports and quality of life subscales with approximately 10-point improvements. Conclusion Acceptable clinical results with the MCL reconstruction technique were achieved in patients suffering from chronic valgus instability.

Objective: This study was undertaken in order to estimate the incidence of repetition of suicide attempt, suicide and all deaths, and to analyse the influence of psychiatric illness and socio-demographic factors on these. Method: The study is a Danish register-based survival analysis that retrieved personal data on socio-economic, psychiatric and mortality conditions from various registers. Hazards were estimated using Cox regression with a time-dependence covariate. Suicide-attempters (2.614) and non-attempters (39.210)were analysed being matched by gender, age and place of residence. Results: The average follow-up period for suicide-attempters was 3.88 years, during which 271 (10.37%) of them died. By comparison, death occurred four times more often among suicide-attempters than among non-attempters. Suicide was far more common among attempters (61, 2.33%) than among non-attempters (16, 0.04%). A proportion of the attempters (31.33%) repeated their attempt within the follow-up period. The most reliable predictors for suicide and death were repetition, suicide attempt method and treatment for mental illness. The most reliable predictors for repetition were age, gender and mental illness. Discussion: Individuals with a history of suicide attempts form a well-defined high-risk group for suicide, and are in need of treatment immediately after the episode. Somatic and psychiatric staff must be informed about the risk factors for subsequent suicidal behaviour after an episode of attempted suicide. Furthermore, departments that are in contact with suicidal individuals need action plans to ensure that all such individuals are discharged to proper treatment immediately after the suicide attempt.

Background: SSRIs are widely used in the treatment of mental illness for both children and adults. Studies have found a slightly increased risk of suicidal thoughts and suicide attempts in young people using SSRIs but SSRIs’ impact on risk for suicides in youth is not well-established. Aim: Is there indication that SSRIs might raise risk for suicide attempts in young people? Methods: We used an observational register-based historical cohort design, a large cohort of all Danish individuals born in 1983–1989 (n = 392,458) and a propensity score approach to analyse the impact from SSRIs on risk for suicide attempts. Every suicide attempt and redeemed prescription of SSRIs was analysed by Cox regression. Results: We found a significant overlap between redeeming a prescription on SSRIs and subsequent suicide attempt. The risk for suicide attempt was highest in the first 3 months after redeeming the first prescription. The hazard ratio for suicide attempts after redeeming a prescription was estimated to 5.23, 95% CI 4.82–5.68. Conclusion: We conclude that the risk of suicide attempt is higher for young people in the first months after redeeming their first prescription for SSRIs, compared to non-users. For SSRI users with lower propensity score (fewer risk factors for SSRIs) the risk of suicide attempt is estimated to be highest. Although the design may miss some explicit reason for prescription of SSRIs and SSRIs might be a marker for those in high risk rather than a causal risk factor, we would recommend systematic risk assessment in the period after redeeming the first prescription.

Aims To investigate the effect of glucagon-like peptide 1 receptor agonist liraglutide on the counter-regulatory hormone response to hypoglycaemia in type 1 diabetes. Methods We conducted a randomized, double-blind, placebo-controlled, single-centre trial, in which a total of 45 adults with type 1 diabetes [mean ± standard deviation age 34.5 ± 11.2 years, BMI 23.9 ± 2.4 kg/m2, glycated haemoglobin (HbA1c) 7.6 ± 0.8%, diabetes duration 16.6 ± 9.4 years] underwent a hypoglycaemic clamp after 4 weeks' crossover treatment with once-daily liraglutide/placebo added to insulin in one of three liraglutide dose groups: 0.6 mg (n = 15); 1.2 mg (n = 14); and 1.8 mg (n = 16). The main outcome measure was glucagon concentration at nadir plasma glucose (2.5 mmol/l). Clinical outcomes were also evaluated. Five participants were withdrawn from the trial; three because of adverse events. All participants were included in the analysis. Results Glucagon concentration at nadir plasma glucose was modest, trending towards lower concentrations at increasing liraglutide dose versus placebo: 34.7 versus 38.1 pg/ml, p = 0.555 (0.6 mg); 28.8 versus 37.2 pg/ml, p = 0.126 (1.2 mg); and 28.4 versus 37.5 pg/ml, p = 0.092 (1.8 mg). There was no difference, however, between liraglutide and placebo in incremental change in glucagon during hypoglycaemia. Other counter-regulatory hormone levels increased during hypoglycaemia with no systematic differences between groups. Glucose infusion rates were significantly lower with liraglutide versus placebo during the clamp. After 4 weeks' treatment, HbA1c remained unchanged in the liraglutide and placebo groups. Greater reductions in insulin dose and body weight were seen with liraglutide versus placebo. Conclusions Liraglutide did not compromise hypoglycaemic responses in type 1 diabetes after 4 weeks' treatment.

Medial patellofemoral ligament (MPFL) reconstruction has recently been broadly accepted as primary surgical treatment in adults. Reconstruction techniques with osseous fixation in femur cannot be used for patients with open growth plates. Operative treatment of patella instability in children therefore is a challenge and requires alternative MPFL reconstruction techniques. Limited knowledge exists concerning outcome after MPFL reconstruction in children and adolescents. This study present clinical outcome in a consecutive single clinic series of children treated with paediatric MPFL reconstruction using a soft tissue femoral fixation technique. Twenty-four MPFL reconstructions in 20 operated children aged 8–16 were included in the study. Indication for surgery was two or more patella dislocations. MPFL reconstruction was performed by looping the released gracilis tendon around the adductor magnus tendon insertion and through drill holes in the proximal medial patella edge. Clinical outcome was evaluated by Kujala score and NRS pain score preoperatively, at 1-year follow-up and final follow-up at 39 months. Outcome was compared with a cohort of 179 adult patients with recurrent patella instability operated with an adult MPFL reconstruction technique. Kujala score improved from 61 (13) to 81 (16). NRS pain score improved from 3.0 (3.1) to 1.5 (1.3) in activity. Four patients (20 %) experienced redislocation within the first postoperative year compared with 5 % in an adult patient population. Five patients (25 %) experienced subluxations. One patient with a redislocation was re-operated with adult MPFL reconstruction technique. Cartilage injury was seen in six patients. There are clinical relevant improvements in knee function and pain after MPFL reconstruction in paediatric patients. Patella stability after MPFL reconstruction using femoral soft tissue graft fixation in paediatric patients was inferior to MPFL reconstruction using bony femoral fixation in adult patients. Case–Control study, Level III.

Insulin resistance and increased demand for insulin secretion occur after successful pancreas transplantation. To investigate the potential effects of immunosuppression and pancreas transplantation on fasting beta-cell function, we studied fasting proinsulin and 32,33 split proinsulin secretion cross-sectionally and longitudinally in segmental pancreatic graft recipients (SPx, n = 18); in whole-pancreas graft recipients (WPx, n = 13); in nondiabetic kidney transplant recipients (Kx, n = 14) and in normal subjects (Ns, n = 14). Basal insulin secretion rates were significantly increased in SPx 15.8 (1.7), WPx 24.4 (4.5) and Kx 22.1 (2.1) vs Ns 9.7 (1.6) pmol min(-1) l(-1), p < 0.05, mean (SEM). Total proinsulin, intact proinsulin and 32,33 split proinsulin concentrations were significantly higher in all the transplanted groups than in normal subjects (p < 0.05), whereas the total proinsulin to C-peptide ratio and the 32,33 split proinsulin ratio were higher in SPx than in WPx, Kx and Ns (< 0.05). In the longitudinal study, beta-cell function in terms of proinsulin secretion remained stable for 1 year. In conclusion, fasting glucose homeostasis in pancreas-kidney transplant recipients is obtained at the expense of increased proinsulin secretion and increased insulin secretion rates, primarily induced by immunosuppression. In segmental pancreas graft recipients, increased fasting proinsulin and 32,33 split proinsulin relative to the number of beta-cells transplanted indicate more stress on the residual beta-cell and therefore higher secretory demand than in whole pancreas transplant recipients.

After pancreas-kidney transplantation, it is difficult to obtain an accurate estimate of the insulin secretion of the pancreas graft, since several pitfalls are involved using peripheral C-peptide and/or insulin measurements in this determination. In this study, the individual kinetic parameters of C-peptide and then the rates of insulin secretion were estimated by two mathematical methods, the deconvolution method and the “combined model” during slow (oral glucose) and fast (intravenous glucagon) changes in insulin secretion in six successful pancreas-kidney transplant recipients with systemic delivery of insulin (Px), six nondiabetic kidney-transplant recipients with portal insulin secretion (Kx), six nondiabetic controls (NS), and six C-peptide-negative insulin-dependent diabetes mellitus patients (IDDM). Decreased C-peptide clearance and basal and poststimulatory hyperinsulinemia were found in both Px and Kx compared with NS ( P < 0.05). Similar glucose responses were observed after intravenous glucagon in all groups, whereas the responses after oral glucose were 30% higher in Px and Kx than in NS ( P < 0.05). During oral glucose and after intravenous glucagon, both mathematical methods resulted in significantly lower maximal and incremental insulin secretion rates (ISR) in Px than in Kx ( P < 0.05). In contrast, calculations of incremental ISR in NS and Px induced by the two β-cell stimuli were about the same but significantly higher in Kx than in NS ( P < 0.05). These results differed markedly from those obtained using peripheral measurements of insulin and C-peptide alone. In conclusion, when C-peptide clearance and insulin metabolism change, such as in pancreas-kidney transplant recipients, accurate evaluation of insulin secretion from the graft can be obtained only by using individual kinetics of the peptides before calculating the ISR. This study also clearly demonstrates that insulin secretion after pancreas transplantation is still defective.

Insulin resistance has been demonstrated in patients with angina pectoris irrespective of detectable atherosclerosis at coronary angiograms. We compared insulin sensitivity, lipid profiles, and exercise capacity in 20 patients with syndrome X, 15 patients with variant angina, and 20 healthy controls to investigate whether the presentation of the insulin resistance syndrome differs between the two patient groups with disparate vascular abnormalities. All patients had angiographically normal coronary arteries. Maximal oxygen uptake (Vo2 (max)) WaS determined at bicycle exercise testing. Insulin sensitivity (S(l)) was assessed by the minimal model analysis of the intravenous glucose tolerance test. Patients with variant angina had significantly lower Vo2(max) than controls (mean ± SE, 25.6 ± 1.5 vs 30.6 ± 1.4 ml x kg-1 x min-1, p < 0.05), whereas VO2 (max) in patients with syndrome X was intermediate (27.1 ± 1.3 ml x kg-1 x min- 1). Compared with controls, patients with syndrome X and variant angina had reduced insulin sensitivity [controls, 1.47 ± 0.16 10-4 x min-1/per pmol/L vs syndrome X 0.86 ± 0.11 10-4 x min-1 per pmol/L and variant angina, 0.96 ± 0.15 x 10-4 x min-1 per pmol/l; analysis of variance, p < 0.05]. Only patients with syndrome X eXhiBited fasting hyperinsulinemia. Patients with syndrome X also had higher fasting concentrations of triglycerides and total cholesterol and lower concentrations of high-density lipoprotein cholesterol than controls. When adjusting S(l) for variances of Vo2(max), differences in S(l) vanished between controls and patients with variant angina but not between controls and patients with syndrome X. Thus syndrome X and variant angina are both associated with insulin resistance, but lipid abnormalities are only prominent in patients with syndrome X. A variable expression in terms of concomitant disturbances of lipid profiles and disparate influences of physical capacity suggests different underlying mechanisms.

A comparison of four different commercial immunometric thyrotropin (TSH) assays (Amerlite R TSH-30 Ultrasensitive assay from Kodak, BeriLux R hTSH from Behring Werke, Delfia R hTSH Ultra from Wallac and IMX R Ultrasensitive hTSH from Abbott) was made by measuring serum TSH in 81 consecutive patients referred to hospital for various reasons with a serum TSH less than 0.8 mIU/I in the IMX assay. The analytical and functional assay sensitivities of each of the assays were analysed. Even though three of the methods had a sensitivity corresponding to third generation assays, we could only demonstrate an overall agreement of serum TSH when comparing two of the kits. The measurements in Delfia Ultra and Berilux showed good agreement ( P = 0.7, paired t -test and bias = 0.003 mIU/1), while the comparisons between the other assays showed different measurements ( P t -test and bias more than 0.07 mIU/1). Differences in the calibrators used in the assays might explain some of the discrepancy, although all methods were calibrated according to the same international standard. Also, differences in the specificity of the TSH monoclonal antibodies used in the assays might be an evident explanation and further studies of the specificity of the monoclonal antibodies are needed. An international collaborative study to clarify reasons for the differences between the TSH assays and to standardize the measurements is recommended.

PURPOSE: The purpose of this randomized controlled study was to compare knee stability, kneeling pain, harvest site pain, sensitivity loss, and subjective clinical outcome after primary anterior cruciate ligament (ACL) reconstruction with either bone-patellar tendon-bone (BPTB) or quadriceps tendon-bone (QTB) autografts in a noninferiority study design.METHODS: From 2005 to 2009, a total of 51 patients were included in the present study. Inclusion criteria were isolated ACL injuries in adults. Twenty-five patients were randomized to BPTB grafts and 26 to QTB grafts. An independent examiner performed follow-up evaluations 1 and 2 years postoperatively. Anteroposterior knee laxity was measured with a KT-1000 arthrometer (MEDmetric, San Diego, CA). Anterior knee pain was assessed clinically and by knee-walking ability. Knee Injury and Osteoarthritis Outcome Score (KOOS) and subjective International Knee Documentation Committee (IKDC) score were used for patient-evaluated outcome.RESULTS: Anterior knee laxity was equal between the 2 groups with KT-1000 values of 1.1 ± 1.4 mm and 0.8 ± 1.7 mm standard deviation (SD) at follow-up in QTB and BPTB groups, respectively (P = .65), whereas positive pivot shift test results were seen less frequently (14% compared with 38%, respectively; P = .03). Anterior kneeling pain, evaluated by the knee walking ability test, was significantly less in the QTB group, with only 7% of patients grading knee walking as difficult or impossible compared with 34% in the BPTB group. At 1 and 2 years' follow-up, there was no difference between the 2 groups in subjective patient-evaluated outcome. The IKDC score was 75 ± 13 patients and 76 ± 16 SD at 1-year follow-up in QTB and BPTB groups, respectively (P = .78). At 2 years, 12 patients were lost to follow-up, resulting in 18 in the BPTB group and 21 in the QTB group.CONCLUSIONS: The use of the QTB graft results in less kneeling pain, graft site pain, and sensitivity loss than seen with BPTB grafts; however, similar anterior knee stability and subjective outcomes are seen. The results of this study show that QTB is a viable option for ACL reconstruction.LEVEL OF EVIDENCE: Level II, randomized controlled clinical trial.

Objective: To estimate the Danish epidemiological long-term incidence rates for suicide attempts in the general population of children and adolescents, and to analyze the impact from single and multiple risk factors on the risk of suicide attempts. Method: We used longitudinal register data from a total cohort of all individuals born between 1983 and 1989 and living in Denmark to calculate incidence rates. From the cohort, we identified all who have attempted suicide, and matched 50 controls to each case. A nested case–control design was used to estimate the impact from risk factors on the risk for index suicide attempts. We established a link to the biological parents and identified risk factors for two generations. Risk factors were analyzed in a conditional logistic regression model. Results: We identified 3718 suicide attempters and 185,900 controls (189,618 individuals, aged 10–21 years). We found increasing incidence rates during the period 1994–2005, and higher incidence rates for girls and the oldest adolescents. Mental illness was the strongest independent risk factor (IRR = 4.77, CI = (4.35–5.23), p < 0.0001), but parental mental illness (psychopharmacological drugs: IRR = 1.27, CI = (1.18–1.37), p < 0.0001) and socio-demographic factors (parents not living together: IRR = 1.38, CI = (1.28–1.48), p < 0.0001) were also significant independent risk factors. Exposure to multiple risk factors increased the risk significantly. Conclusions: Suicide attempt is a multi-factorial problem, and a problem on the increase in the period studied. Individuals exposed to multiple risk factors are at the highest risk for suicide attempts, and when spotted or in contact with authorities they should be given proper care and treatment to prevent suicide attempts and death.

The effect of sham feeding on glucose metabolism was studied in eleven normal subjects. At random, one intravenous glucose tolerance test (25 g glucose/4 min) was preceded by 15 minutes of pure sham feeding (the sight and smell of a meal but not the taste) which continued for the first 15 minutes after the intravenous glucose load. Pancreatic polypeptide increased significantly during sham feeding and decreased significantly in response to the glucose injection. The glucose disappearance rate was significantly improved from 1.56 +/- 0.22 to 2.07 +/- 0.33 min-1 when the glucose tolerance test was preceded by sham feeding (p = 0.02). Incremental areas of plasma insulin, plasma C-peptide, and insulin secretion rates were not significantly influenced by sham feeding. We conclude that sham feeding by the sight and smell of food improves glucose tolerance in normal subjects without alteration in insulin secretion.

To assess individual factors responsible of overall glucose tolerance after successful pancreas transplantation, an i.v. glucose tolerance test, with frequent blood sampling and tolbutamide administration to elicit a second insulin response was used to estimate insulin sensitivity (SI) and glucose effectiveness (SG) with Bergman's minimal model. Insulin secretion was calculated from the combined insulin-C-peptide kinetics method. These parameters were quantified in identically immunosupressed transplants: ISPx, four segmental pancreas recipients with impaired glucose tolerance; TSPx, five segmental pancrease recipients with normal glucose tolerance; WPx, five whole pancreas recipients with normal glucose tolerance; and in two controls groups, Kx, eight nondiabetic kidney recipients, and Ns, eight normal subjects. All participants had normal fasting plasma glucose and normal glycosylated hemoglobin A1C levels. The glucose tolerance KG value was significantly reduced only in ISPx compared with Ns (P0.05). SI was reduced by 60% in ISPx, WPx, and Kx compared with normal subjects (P0.05), whereas SI was reduced by 30% in TSPx compared with normal controls (P = NS). The reduction in SG was the same in all pancreas transplanted groups, as compared to Kx and Ns (by 33% and 40%, respectively, P0.05). The first-phase insulin secretion (0-5 min) was markedly reduced in ISPx and TSPx compared with Ns (by 76% and 50%), to Kx (by 84% and 66%) and to WPx (by 73% and 45%), respectively (P0.05), but similar to Ns in WPx. The overall incremental insulin secretion was reduced in ISPx compared with Ns, WPx, and Kx (by 38%, 62%, and 73%, respectively, P0.05) and reduced in TSPx compared to WPx and Kx (by 47% and 67%, respectively, P0.05) Ns secreted 43% of the total amount of insulin during the first phase the corresponding value was only 13% in ISPx vs. 24% in TSPx, 24% in Kx, and 25% in WPx, respectively (P0.05). In conclusion, after pancreas transplantation, the overall glucose tolerance is determined by the net effect of reductions in insulin sensitivity and glucose effectiveness and in the adaptability of the beta-cells to ensure sufficient insulin secretion. beta-cell function was impaired in both the whole pancreas and segmental transplant recipients, and the failure to increase insulin secretion sufficiently leads to glucose intolerance.

There seems to be an increased risk of children and adolescents committing or attempting suicide after contact with a psychiatric department. Children and adolescents living in families with low socio-economic status (SES) might have an especially increased suicide attempt risk.A complete extraction of Danish register data for every individual born in the period 1983-1989 was made. Of these 403,431 individuals, 3,465 had attempted suicide. In order to control for confounder effects from gender, age and calendar-time, a nested case-control study was designed. A total population of 72,765 individuals was used to analyze the risk of suicide attempts after contact with a psychiatric department. The case-control data were analyzed using conditional logistic regression.This study shows that a child/adolescent's risk of suicide attempt peaks immediately after discharge from last contact with a psychiatric department. The risk of suicide attempt is highest for children and adolescents suffering from personality disorders, depression and substance use disorders. Children and adolescents with previous contact with a psychiatric department and parental income in the lowest third have a significantly higher risk of suicide attempt. Suicide attempters were more likely to have been given several different diagnoses and several different psychopharmacological drugs prior to their attempted suicide.The findings in this study highlight the need for psychopathology assessment in every case of attempted suicide. This study also shows that well-known risk factors such as contact with a psychiatric department do not affect all individuals in the same way. Individuals from families with low SES had the highest risk. This suggests that the presence of factors influencing both vulnerability and resiliency, e.g., family level of SES, needs to be included in the assessment.

The aim of the present study is to present epidemiology and clinical outcome after revision anterior cruciate ligament (ACL) reconstruction with an intermediate follow-up time of up to 9 years. A retrospective study of patients treated with ACL revision from 2001 to 2007 at a university referral clinic was conducted. Study follow-up was performed in 2010; this follow-up included objective IKDC scores, KOOS, Tegner and SANE subjective scores, KT-1000 knee laxity measurements and registration of reoperations and complications. One hundred and twenty-eight patients were available for follow-up. Median follow-up time was 6 (2–9) years. Mean age was 32 years, 50% were men. Eleven percent required staged procedures, 30% were reconstructed with allograft tendons and 23% had collateral ligament reconstruction in combination with the ACL revision. SANE knee global score (0–100) was 74 at follow-up, KOOS sub-scores were preoperatively 66, 69, 77, 42 and 39 for pain, symptoms, activity of daily living, sports and quality of life, respectively. At follow-up, scores were 70, 76, 81, 50 and 50, respectively. Sport and quality of life scores increased significantly. KT-1000 was 6.2 mm preoperatively and 2.5 at follow-up (P

This study tested the hypothesis that serial dilation of the tibial tunnel could provide a stronger anchorage of the graft-fixation-device complex compared to traditional extraction drilling. Forty patients (22 men and 18 women) undergoing ACL reconstruction were randomized to either extraction drilling (group ED) or compaction by serial dilation (group SD) of the tibial tunnel. Tantalum beads were placed in the tibia, femur, and in the hamstring graft. Radiostereometric analysis (RSA) was performed postoperatively and again after 6, 12, and 24 weeks. Migration of graft in the bone tunnels as well as knee laxity was assessed using RSA and a TELOS stress device. Six patients (three men and three women) were excluded during follow-up, which resulted in 17 patients in group ED [median age 30 years (range 20–50)] and 17 patients in group SD [median age 32 years (range 20–49)]. The mean migration of the graft in the tibial bone canal after 3 months was 1.3 (SD 0.6) mm in group ED and 0.8 (SD 0.5) mm in group SD (P = 0.02). The overall knee laxity after 3 months was 13.0 (SD 4.0) mm in group ED and 10.9 (SD 3.1) mm in group SD. This study found less slippage of the hamstring graft in the tibial bone canal in the serial dilated group compared to the extraction drilling group. The clinical relevance of the difference is unknown. No difference in stress radiographic knee laxity was found between the two groups.

BackgroundThere is a lack of specific knowledge about the dose–response effect of multiple parental risk factors for suicide attempts among children and adolescents. The aim of this study was to determine the dose–response effect of multiple parental risk factors on an offspring's risk for suicide attempt.MethodWe designed a population-based two-generation nested case–control study and used Danish register data. A population of 403 431 individuals born between 1983 and 1989 was sampled. Among these, 3465 (0.8%) were registered as having had a suicide attempt. Twenty controls were matched to each case and a link to the offspring's biological parents was established.ResultsThere was a dose–response relationship between the number of exposures and the risk of suicide attempts, with the increased risk seeming to be a multiplicative effect. Parental suicide, suicide attempt, psychiatric illness and low level of income were all significant independent risk factors for offspring's suicide attempts.ConclusionsKnowledge of the effect of multiple risk factors on the likelihood of suicide attempts in children and adolescents is important for risk assessment. Dose–response effects of multiple parental risk factors are multiplicative, but it is rare for children and adolescents to be exposed to multiple parental risk factors simultaneously. Nevertheless, they should be considered along with the offspring's own multiple risk factors in determining the overall risk of a suicide attempt. Further research incorporating both parental and offspring's risk factors is indicated to determine the overall dose–response effect of multiple risk factors.

The purpose was to expand the understanding of schizophrenia development in children and adolescents. An age- and gender-specific analysis of children and adolescents diagnosed with schizophrenia (F20.xx) was performed. The analysis included calculation of incidence rates of schizophrenia, schizophrenia subtypes, and an account of occurrence of any registered psychiatric diagnoses prior to first schizophrenia diagnosis.Patients aged 0-21 years diagnosed with schizophrenia (F20.xx) and registered in the Danish Psychiatric Central Research Register in 1994-2007 were included.The cohort consisted of 3,065 patients aged 6-21 years. Incidence rates vary with age and gender, and have been increasing in recent years. Boys have earlier onset and higher incidence rates than girls. The most common schizophrenia subtypes were paranoid (F20.0; 44.0%) and unspecified (F20.9; 28.7%). Three in every four patients had contact with the psychiatric hospital system prior to first schizophrenia diagnosis.Schizophreniform symptomatology tends to overlap with other psychiatric disorders, and diagnostic stability is low. The diagnosis schizophrenia should be systematically included in diagnostic deliberations. Qualitative studies describing and analysing early psychopathology in children and adolescents with schizophrenia will improve the present knowledge.

Udgivelsesdato: 2008-Nov-20 The literature suggests that the risk of suicide is high within the first weeks after discharge from psychiatric care, but practically no studies have estimated the risk of suicide attempt after discharge from psychiatric care. The aim of this study was to examine the risk level for suicide attempt after discharge from psychiatric care, and to control for effects from psychiatric diagnoses, number and length of previous admission. An analysis of the role of co-morbid substance use disorder in suicide attempts risk was completed. The study is a Danish register-based nested case-control study; 3037 cases were identified from Register for Suicide Attempts, and 60,295 individuals, matched by gender and age, were identified for comparison. Retrospective personal data on psychiatric care was obtained from the Danish Psychiatric Central Register. Risk of suicide attempts was estimated by the use of conditional logistic regression. We found a significant high peak in risk of suicide attempts in the first weeks after discharge from psychiatric care. The risk was lowered as time passed by. Suicide attempt risk was not equally distributed across various psychiatric diagnoses, and co-morbidity of substance abuse with mental illness raised risk in an additive way. We found only small gender differences in risk. In order to lower the risk of suicide attempts, we need to improve after-care when discharging from psychiatric care. A differentiation between the possibilities of after-care for different mental illnesses is needed.

Insulinomas are rare neuroendocrine tumors with an incidence of 4 per 1,000,000 person-years, being even rarer during pregnancy. During pregnancy most cases are recognized or become symptomatic during the first trimester. A 29-year-old woman, primigravida, was hospitalized in the 38th gestational week due to slurred speech, weakness and slow reaction patterns. An electroencephalogram and computed tomography scan of the brain and blood samples were normal. Blood pressure was 170-145/110-95 mmHg, albuminuria was moderate and there was moderate edema of the ankles. Labor started spontaneously the third day, 62 h after of hospitalization, and the patient gave birth to a healthy girl with no neonatal problems. Fourteen hours after delivery, the patient became comatose and developed universal clonic seizures. At the same time plasma glucose was

Udgivelsesdato: 2008-Aug PURPOSE: The purpose of this study was to evaluate the effect of surgical reinsertion of the medial patellofemoral ligament (MPFL) to the adductor tubercle compared with conservative treatment in patients with primary dislocation of the patella. METHODS: Eighty patients with primary patella dislocation were included in the study. Delayed arthroscopy (mean, 50 days after injury) was performed to assess cartilage injury and status. During arthroscopy, patients were randomized to surgical reinsertion of the MPFL or to conservative treatment. Conservative treatment was use of a brace with 0 degrees to 20 degrees motion for the first 2 weeks after dislocation. Patients were followed up for 2 years. The incidence of recurrent patella dislocation was recorded along with the clinical Kujala scores and Knee Injury and Osteoarthritis Outcome Scores. RESULTS: The redislocation rates were 17% and 20% in the operative and conservative treatment groups, respectively (P = not significant). Kujala scores were 85 and 78 in the operative and conservative treatment groups, respectively (P = .07). The patella stability subscore was significantly higher in the operative group. No difference in Knee Injury and Osteoarthritis Outcome Scores was found. CONCLUSIONS: Delayed primary repair of the MPFL by use of an anchor-based reattachment to the adductor tubercle without vastus medialis obliquus repair after primary patella dislocation does not reduce the risk of redislocation nor does it produce any significantly better subjective functional outcome based on the Kujala knee score. Only the specific subjective patella stability score was improved by MPFL repair compared with conservative treatment. LEVEL OF EVIDENCE: Level I, therapeutic randomized controlled trial.

Udgivelsesdato: 2008-Jan PURPOSE: We present clinical results in a case series of 44 patients with medial patellofemoral ligament (MPFL) reconstruction with 12 to 32 months' follow-up. METHODS: Reconstruction was performed via gracilis tendon autograft looped through 2 transverse 4.5-mm drill holes in the patella and fixed at the natural MPFL insertion site on the medial femoral condyle with an interference screw. At follow-up, Kujala scores, Knee Injury and Osteoarthritis Outcome Scores, objective knee function, complications, and reoperations were assessed. RESULTS: Only 1 patella redislocation was observed. Subluxation occurred in 3 patients, whereas 4 patients had chronic pain at follow-up, all of whom had cartilage injury at surgery. The Kujala knee function score improved overall from 46 points (range, 12 to 67 points) to 84 points (range, 62 to 100 points) at follow-up. CONCLUSIONS: MPFL reconstruction with double transverse patella drill holes and a gracilis tendon graft provides good postoperative patellar stability. Postoperative pain seems to be related to the degree of patellofemoral injury found at surgery. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

We examined suicide attempters' use of health insurance services as part of an effort to prevent suicidal behaviour.The research project was a register-based case control study, where cases were persons residing in the County of Funen, Denmark, who made a suicide attempt resulting in contact with a hospital. Controls were matched with respect to gender, age and county of residence on the date of the first registered suicide attempt (index attempt). Data about services paid for by the public health insurance program were collected from the Prevention Register. The data were analyzed using conditional logistic regression.In the calendar year prior to an index attempt, suicide attempters consulted health professionals, i.e., general practitioners, psychologists or psychiatrists, more often. Gender and age differences were small.Suicide attempters consult health insurance professionals, especially GPs, more often, and GPs' specific role in the prevention of attempted suicide is discussed.

Blunted insulin-stimulated endothelial function may be a mechanism for the development of atherothrombotic disease in type 2 diabetes, but it is unknown whether hypoglycemic drug therapy can modulate this abnormality. We studied patients with type 2 diabetes and stable ischemic heart disease (n = 28) and lean, healthy control subjects (n = 31). Forearm blood flow was measured by venous occlusion plethysmography during dose-response studies of acetylcholine (ACh) and sodium nitroprusside (SNP) infused into the brachial artery. In the patients and 10 healthy control subjects, ACh was repeated after intrabrachial infusion of insulin. Patients were restudied after 2 months of insulin therapy with four daily subcutaneous injections (treatment group, n = 19) or without hypoglycemic drug therapy (time control group, n = 9). Insulin infusion raised venous serum insulin in the forearm to high physiological levels (133 +/- 14.6 mU/l in patients) with a minor increase in systemic venous serum insulin. This increased the ACh response by 149 +/- 47, 110 +/- 33, 100 +/- 45, and 106 +/- 44% during the four ACh doses in healthy control subjects (P < 0.0001) but had no effect in patients (P = 0.3). After 2 months, HbA(1c) in the treatment group had decreased from 10.0 +/- 0.4 to 7.5 +/- 0.2%. Although neither the ACh response (P = 0.09) nor the SNP response (P = 0.4) had changed significantly, insulin stimulation had a significant effect, as the ACh response increased by 58 +/- 25, 84 +/- 66, 120 +/- 93, and 69 +/- 36% (P = 0.0002). In the time control group, insulin stimulation remained without effect after 8 weeks (P = 0.7). In conclusion, insulin therapy partly restores insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease.

To detect and understand the changes in beta-cell function in the pathogenesis of type 2 diabetes, an accurate and precise estimation of prehepatic insulin secretion rate (ISR) is essential. There are two common methods to assess ISR, the deconvolution method (by Eaton and Polonsky)-considered the "gold standard"-and the combined model (by Vølund et al.). The deconvolution method is a 2-day method, which generally requires separate assessment of C-peptide kinetics, whereas the combined model is a single-day method that uses insulin and C-peptide data from a single test of interest. The validity of these mathematical techniques for quantification of insulin secretion have been tested in dogs, but not in humans. In the present studies, we examined the validity of both methods to recover the known infusion rates of insulin and C-peptide mimicking ISR during an oral glucose tolerance test. ISR from both the combined model and the deconvolution method were accurate, i.e., recovery of true ISR was not significantly different from 100%. Furthermore, both maximal and total ISRs from the combined model were strongly correlated to those obtained by the deconvolution method (r = 0.89 and r = 0.82, respectively). These results indicate that both approaches provide accurate assessment of prehepatic ISRs in type 2 diabetic patients and control subjects. A simplified version of the deconvolution method based on standard kinetic parameters for C-peptide (Van Cauter et al.) was compared with the 2-day deconvolution method, and a close agreement was found for the results of an oral glucose tolerance test. We also studied whether C-peptide kinetics are influenced by somatostatin infusion. The decay curves after bolus injection of exogenous biosynthetic human C-peptide, the kinetic parameters, and the metabolic clearance rate were similar whether measured during constant peripheral somatostatin infusion or without somatostatin infusion. Assessment of C-peptide kinetics can be performed without infusion of somatostatin, because the endogenous insulin concentration remains constant. Assessment of C-peptide kinetics with and without infusion of somatostatin results in nearly identical secretion rates for insulin during an oral glucose tolerance test.

Objective: The most accurate way to measure urinary iodine excretion in epidemiological surveys is still debated. We propose a new principle of estimating iodine excretion based on casual urine samples. Material and methods: A total of 123 24 h urine samples and corresponding casual urine samples were collected from 31 subjects. Iodine excretion was expressed as 24 h iodine excretion and three different estimates: iodine concentration in the casual sample, iodine=gram creatinine in the casual sample, and the new principle — iodine=creatinine ratio in the casual sample, adjusted for expected creatinine excretion of the individual. Results: All three estimates based on casual urine samples correlated significantly to 24 h values with a r (Pearson) of 0.37 for iodine concentration, 0.61 for iodine=creatinine ratio and 0.62 for the age- and sex-adjusted iodine=creatinine ratio. The median iodine excretion in the entire group was 143mg=day in 24 h samples, 87mg=l as iodine concentration, 77mg=g creatinine as iodine=creatinine ratio and 126mg=day as age- and sex-adjusted iodine=creatinine ratio. Conclusion: Age- and sex-adjusted iodine=creatinine ratio is a more accurate and unbiased estimate of iodine excretion in epidemiological surveys of adults than the two most frequently used estimated: iodine concentration and iodine=gram creatinine, as these two estimates may introduce a bias depending on the composition of the investigated group. The adjusted iodine=creatinine ratio is superior to the other estimates, especially when individual estimates of 24 h iodine excretion is required or cohorts of selected groups are investigated. Sponsorship: This work was supported by grants from the Medical Research Foundation Region Greater Copenhagen, Faroe Islands and Greenland; the Wedell-Wedellsborg Foundation; Musikforlaeggerne Agnes and Knut Morks Foundation. Descriptors: iodine; urine; methods; epidemiology; evaluation studies European Journal of Clinical Nutrition (2000) 54, 361‐363

OBJECTIVE To examine glucose metabolism, blood pressure, physical fitness, and lipid metabolism in adult untreated women with Turner's syndrome compared with a group of normal women and to examine the effects of female sex hormone substitution on these factors. RESEARCH DESIGN AND METHODS A total of 26 patients with Turner's syndrome were examined before and during sex hormone replacement with 17β-estradiol and norethisterone, and an age-matched control group (n = 24) was examined once. A frequently sampled intravenous glucose tolerance test was applied with minimal model assessment. We also performed an oral glucose tolerance test, measurement of 24-h ambulatory blood pressure, and assessment of physical fitness and lipid metabolism. RESULTS Insulin sensitivity (SI) and glucose effectiveness (SG) were similar in Turner's syndrome patients and control subjects, whereas the acute insulin response (P = 0.03) was lower in Turner's syndrome patients, and no change was seen during sex hormone treatment. Abnormal glucose tolerance was found in 50% of Turner's syndrome patients before and 78% during treatment with sex hormones. Fat-free mass (FFM; P = 0.0005) and physical fitness (P = 0.002) were lower in Turner=s syndrome subjects compared with control subjects. During treatment, an increase in FFM (P = 0.001) and physical fitness (P = 0.02) was seen in Turner's syndrome patients. Blood pressure was increased in Turner's syndrome, and a decrease was seen in diastolic blood pressure during treatment with sex hormones. CONCLUSIONS Turner's syndrome is associated with glucose intolerance, diminished first-phase insulin response, elevated blood pressure, reduced FFM, and physical fitness. Sex hormone administration causes a deterioration in glucose tolerance, increases FFM and physical fitness, and has beneficial effects on blood pressure. The deleterious effect on glucose tolerance may be mediated by norethisterone, a gestagen known to have androgenic effects.

OBJECTIVE High intake of trans fatty acids and saturated fatty acids (SFAs) is known to increase the risk of coronary heart disease. We studied the effects of diets enriched in various fatty acids on postprandial insulinemia and fasting serum levels of lipids and lipoproteins in obese patients with NIDDM. RESEARCH DESIGN AND METHODS Sixteen obese NIDDM patients were studied in a free-living outpatient regimen. After a run-in period, the patients received three different isocaloric diets for 6 weeks using a randomized crossover design. The patients were instructed to keep the energy intake from carbohydrate and protein constant at 50 and 20 E% (percent of energy intake), respectively, on all three diets. The fat composition of the diets differed: saturated fat (SAT) diet (20 E% SFAs, 5 E% polyunsaturated fatty acids [PUFAs], and 5 E% monounsaturated fatty acids [MUFAs]) versus cis monounsaturated fatty acid (CMUFA) diet (20 E% cis-MUFAs, 5 E% PUFAs, and 5 E% SFAs) versus trans monounsaturated fatty acid (TMUFA) diet (20 E% trans-MUFAs, 5 E% PUFAs, and 5 E% SFAs). Fasting serum levels of lipids and lipoproteins were measured at baseline and in the fasting state before meal tolerance tests at the end of each study period. Insulin secretion was assessed from incremental serum insulin and C-peptide responses during the meal tests. RESULTS BMI, waist-to-hip ratio, and glycemic control remained stable throughout the study. After meal stimulation, postprandial glycemic responses were similar on all diets; however, serum insulin and C-peptide responses were greater following the TMUFA and SAT diets than following the baseline or CMUFA diets (P < 0.05). No statistical difference was found in fasting levels of serum lipids (total cholesterol, triglyceride, phospholipid, and nonesterified fatty acids) or lipoproteins of HDL cholesterol, VLDL cholesterol, LDL cholesterol, and apolipoprotein B between diets. CONCLUSIONS In the presence of unchanged glycemia, both dietary trans fatty acids and SFAs induce an increase in postprandial insulinemia in obese patients with NIDDM.

To determine potential abnormalities in beta-cell function after pancreas transplantation, the secretory capacity of the pancreatic grafts was assessed by measuring the glucose-potentiating effect on arginine-induced insulin secretion in recipients of cadaveric segmental (SPx; n = 8) and whole organ pancreas grafts (WPx; n = 6) and compared to that in nondiabetic kidney transplant recipients (Kx; n = 6) and normal controls (Ns; n = 7). alpha-Cell adaptation to increasing hyperglycemia and the glucagon response to arginine stimulation were also studied. The secretory capacity of the beta-cell to arginine-induced (5 g L-arginine) insulin secretion was measured at fasting plasma glucose and 15 and 30 mmol/L glucose. Insulin secretion was evaluated by the calculation of insulin secretion rates. Insulin sensitivity was markedly reduced in all three transplanted groups compared to that in normal subjects (P < 0.05). The prestimulation insulin secretion rate and maximal insulin secretion rate in response to hyperglycemia and arginine were significantly lower in SPx than in WPx, Kx, or Ns (P < 0.05). The incremental amount of insulin secreted in response to arginine was reduced by 40-70% in SPx depending on glycemia compared to that in all other groups (P < 0.05), among which there were no statistical differences. Both SPx and WPx demonstrated suppression of glucagon release in response to graded hyperglycemia, but failure to adequately suppress arginine-induced glucagon release. In conclusion, recipients of cadaveric segmental pancreas grafts display a markedly reduced maximal insulin secretory reserve capacity. This impairment was primarily due to an insufficient beta-cell mass. Taking the concomitant insulin resistance into account, recipients of a cadaver whole organ pancreas graft had an impaired insulin secretory reserve capacity as well.

Survival in congestive heart failure is related to plasma catecholamines and atrial natriuretic peptide at rest, but the prognostic importance of changes during exercise is unknown. The aim of this study was to evaluate the prognostic value of catecholamines and atrial natriuretic peptide at rest and during maximal exercise in congestive heart failure, and to compare it to clinical and exercise test variables and left ventricular ejection fraction. One hundred ninety consecutive patients (136 men and 54 women; median age, 66 years; range, 42-75 years) with clinically stable congestive heart failure were included. Sixteen patients were in New York Heart Association class I, 87 in class II, 83 in class III, and 4 in class IV. Left ventricular ejection fraction was 0.30 (range, 0.06-0.74). Total survival after 1 year was 79%, after 2 years, it was 68%. Prognostic variables at univariate analysis were: plasma noradrenaline at rest (P.0001), plasma adrenaline at rest (P = .049), and atrial natriuretic peptide at rest (P = .016). During exercise, plasma catecholamines and plasma atrial natriuretic peptide increased significantly; the change, however, was not related to survival. Six variables carried significant, independent prognostic information in a multivariate analysis: left ventricular ejection fraction (P = .03), plasma noradrenaline at rest (P = .009), New York Heart Association class III + IV (P = .005), increase in heart rate during exerciseor = 35 min-1 (P.0001), serum creatinine121 mumol/L (P = .004), and serum urea7.6 mmol/L (P = .007). Patients with congestive heart failure have a poor survival despite intensive medical treatment. Plasma catecholamines and plasma atrial natriuretic peptide are elevated at rest and rises further during exercise; the increase, however, is not related to mortality. Plasma noradrenaline at rest contributes with further prognostic information despite knowledge of clinical and exercise variables and was the only neurohormonal variable with independent, significant prognostic information on survival.

Nocturnal fluctuations in subcutaneous blood flow in the lower leg and foot were measured during sleep in Type 1 diabetic patients without autonomic neuropathy. Subcutaneous blood flow was measured, simultaneously, 100 mm above the malleolus on the medial aspect of the right lower leg and at the dorsum of the left foot in 10 diabetic patients, and on the right lower leg only in 10 normal human subjects over 12-20 h. The 133Xe wash-out technique, portable CdTe (Cl) detectors and a portable data storage unit were used. The tracer depots were applied by means of the epicutaneous, atraumatic labelling technique. In diabetic patients, subcutaneous blood flow increased 102 +/- 68% in the lower leg and 111 +/- 98% in the foot at 113 +/- 32 min and 107 +/- 37 min, after going to sleep. The hyperaemic phase lasted 128 +/- 43 min and 150 +/- 42 min, respectively. The hyperaemic response was not different from that in the control subjects (89 +/- 61%). There was no significant correlation between the absolute hyperaemia in the leg and that in the foot. In conclusion, Type 1 diabetic patients without autonomic neuropathy have normal nocturnal hyperaemia during sleep.