Trends in depressive symptoms, anxiety symptoms and visits to healthcare specialists: a national study among Icelandic adolescents

AIMS: The aim of the study was to examine trends in adolescent depression and anxiety symptoms from 1997 to 2006, using four time-points (1997, 2000, 2003, and 2006), and adolescent mental health service use in the same period, using three time-points (1997, 2000, and 2006). METHODS: Four cross-sectional population-based samples of 14- and 15-year-old students, attending the compulsory 9th and 10th grades of the Icelandic secondary school system, completed questionnaires relating to mental health. In total, 21,245 students participated in the four studies. RESULTS: Anxiety symptoms increased significantly for both boys and girls, throughout the period from 1997 to 2006. Depressive symptoms increased significantly for girls, while there were no significant changes in depression among boys. During the same time period, the proportion of adolescents who visited healthcare specialists, i.e. psychiatrists, psychologists and social workers, increased significantly. The results revealed that regular visits (six times or more during 1 year) to psychiatrists and psychologists increased significantly over the same period among girls but not among boys. CONCLUSIONS: The findings show that symptoms of depression and anxiety have increased among adolescents in Iceland. Future work would benefit from further research into the trends in risk and protective factors associated with these outcomes. The findings call particular attention to the increasing risk for depression and anxiety symptoms among girls.     

Estrogen–progestin use and breast cancer characteristics in lean and overweight postmenopausal women

Purpose

We examined acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) events among 9679 women treated for breast cancer on four adjuvant Alliance for Clinical Trials in Oncology trials with >90 months of follow-up in order to better characterize the risk for AML/MDS in older patients receiving anthracyclines.

Methods

We used multivariable Cox regression to examine factors associated with AML/MDS, adjusting for age (≥65 vs. <65 years; separately for ≥70 vs. <70 years), race/ethnicity, insurance, performance status, and anthracycline receipt. We also examined the effect of cyclophosphamide, the interaction of anthracycline and age, and outcomes for those developing AML/MDS.

Results

On Cancer and Leukemia Group B (CALGB) 40101, 49907, 9344, and 9741, 7290 received anthracyclines; 15% were in the age ≥65 and 7% were ≥70. Overall, 47 patients developed AML/MDS (30 AML [0.3%], 17 MDS [0.2%]); 83% of events occurred within 5 years of study registration. Among those age ≥65 and ≥70, 0.8 and 1.0% developed AML/MDS (vs. 0.4% for age <65), respectively. In adjusted analyses, older age and anthracycline receipt were significantly associated with AML/MDS (adjusted hazard ratio [HR] for age ≥65 [vs. <65] = 3.13, 95% confidence interval [CI] 1.18–8.33; HR for anthracycline receipt [vs. no anthracycline] = 5.16, 95% CI 1.47–18.19). There was no interaction between age and anthracycline use. Deaths occurred in 70% of those developing AML/MDS.

Conclusions

We observed an increased risk for AML/MDS for older patients and those receiving anthracyclines, though these events were rare. Our results help inform discussions surrounding anticipated toxicities of adjuvant chemotherapy in older patients.

     

A multi-level developmental approach towards understanding adolescent mental health and behaviour: rationale,design and methods of the LIFECOURSE study in Iceland

Purpose

Identifying and understanding modifiable risk and protective factors that can inform early detection and intervention to prevent adolescent emotional problems and harmful behaviours is among the most pressing modern-day public health challenges. This paper describes the rationale, objectives, methods, and anticipated outcomes of the LIFECOURSE study, a multi-level, bio-psychosocial prospective study designed to advance our understanding of factors that shape adolescent mental health and behaviour.

Methods

Conducted by the Icelandic Centre for Social Research and Analysis at Reykjavik University, LIFECOURSE is a longitudinal population-based developmental study of Icelandic adolescents born in 2004. The study utilizes a comprehensive multi-informant assessment of individual, societal and biological factors measured across the lifespan. Data assembly and collection were conducted from 2016–2020 and utilize both retrospective and prospective data sources: (a) retrospective registry data assembled from seven national databases, (b) prospectively collected social surveys and (c) biomarker samples.

Results

Of the 3914 eligible adolescents, 60.8% (n = 2378) provided informed parental consent and student assent to participate in the study, with approximately half of the participants being female (n = 1175, 49.4%) and the majority being born in the capital area (n = 1455; 61.2%). The coverage of available data from the national databases and participation in the social surveys ranged from 81.7 to 100%.

Conclusions

Major gaps remain in our knowledge of how individual, societal and biological factors across the lifespan—from early life to adolescence—interact and shape the risk for emotional problems and harmful behaviours during adolescence. The LIFECOURSE study was designed to address this knowledge gap.

     

New 3-alkylamino-4H-thieno-1,2,4-thiadiazine 1,1-dioxide derivatives activate ATP-sensitive potassium channels of pancreatic beta cells

Compound 1a (NN414) is a potent opener of Kir6.2/SUR1 K(ATP) channels. Compound 1a inhibits insulin release in vitro and in vivo and preserves beta cell function in preclinical animal models suggesting that such a compound could find use in treatment or prevention of type 1 and type 2 diabetes. The crystal structure and a convergent synthesis of 1a are presented together with a range of new analogues of 1a. Several compounds, e.g., 6-chloro-3-(1-methyl-1-phenylethyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (1h), were found to be potent openers of Kir6.2/SUR1 K(ATP) channels and were able to suppress glucose-stimulated insulin release from rat islets in vitro (EC(50) = 0.04 +/- 0.01 muM) and in vivo after intravenous or peroral administration to hyperinsulinemic obese Zucker rats (ED(50) = 4.0 mg/kg). Structural modifications of this series of K(ATP) channel openers have provided compounds with promising pharmacokinetic properties indicating that brief periods of beta cell rest can be achieved.     

Midlife metabolic factors and prostate cancer risk in later life

Metabolic syndrome is associated with several cancers, but evidence for aggressive prostate cancer is sparse. We prospectively investigated the influence of metabolic syndrome and its components on risk of total prostate cancer and measures of aggressive disease in a cohort of Icelandic men. Men in the Reykjavik Study (n = 9,097, enrolled 1967–1987) were followed for incident (n = 1,084 total; n = 378 advanced; n = 148 high‐grade) and fatal (n = 340) prostate cancer until 2014. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for (1) measured metabolic factors at cohort entry (body mass index (BMI), blood pressure, triglycerides, fasting blood glucose) and (2) a metabolic syndrome score (range 0–4) combining the risk factors: BMI ≥30 kg/m²; systolic blood pressure (SBP) ≥130 or diastolic blood pressure (DBP) ≥85 mm Hg or taking antihypertensives; triglycerides ≥150 mg/dl; fasting blood glucose ≥100 mg/dl or self‐reported type 2 diabetes. Hypertension and type 2 diabetes were associated with a higher risk of total, advanced, high‐grade, and fatal prostate cancer, independent of BMI. Neither BMI nor triglycerides were associated with prostate cancer risk. Higher metabolic syndrome score (3–4 vs 0) was associated with a higher risk of fatal prostate cancer (HR 1.55; 95% CI: 0.89, 2.69; p trend = 0.08), although this finding was not statistically significant. Our findings suggest a positive association between midlife hypertension and diabetes and risk of total and aggressive prostate cancer. Further, metabolic syndrome as a combination of factors was associated with an increased risk of fatal prostate cancer.     

Effect of enalapril therapy on ventilatory pulmonary function tests in hypertensive patients

Fifty newly diagnosed nonsmoker patients suffering from mild to moderate hypertension (diastolic BP 90 to 114 mmHg), randomly selected and not having respiratory or other systemic diseases which may affect pulmonary functions were subjected to thorough interrogation and clinical examination. Twenty five normal age and sex matched healthy volunteers served as control. All patients and controls were subjected to ventilatory pulmonary function tests (VPFT), done by computerized spirometer. Hypertensive patients were put on oral enalapril, doses were titrated and maintained on 2.5 to 10 mg once daily. Twenty percent of the total hypertensive patients reported mild to moderate dry cough and was more frequently observed among females (27%). Significant decline was observed in MEF 50% and MEF 25% of vital capacity values (p 0.0204 and 0.0001) after 10 days of enalapril therapy. These two VPFT parameters showed significantly higher decline among patients who developed cough as compared to patients who did not develop cough. Decline in VPFT parameters were directly related to doses of enalapril.     

A potential impact of DNA repair on ageing and lifespan in the ageing model organism Podospora anserina: Decrease in mitochondrial DNA repair activity during ageing

The free radical theory of ageing states that ROS play a key role in age-related decrease in mitochondrial function via the damage of mitochondrial DNA (mtDNA), proteins and lipids. In the sexually reproducing ascomycete Podospora anserina ageing is, as in other eukaryotes, associated with mtDNA instability and mitochondrial dysfunction. Part of the mtDNA instabilities may arise due to accumulation of ROS induced mtDNA lesions, which, as previously suggested for mammals, may be caused by an age-related decrease in base excision repair (BER).Alignments of known BER protein sequences with the P. anserina genome revealed high homology. We report for the first time the presence of BER activities in P. anserina mitochondrial extracts. DNA glycosylase activities decrease with age, suggesting that the increased mtDNA instability with age may be caused by decreased ability to repair mtDNA damage and hence contribute to ageing and lifespan control in this ageing model.Additionally, we find low DNA glycosylase activities in the long-lived mutants grisea and ΔPaCox17::ble, which are characterized by low mitochondrial ROS generation.Overall, our data identify a potential role of mtDNA repair in controlling ageing and life span in P. anserina, a mechanism possibly regulated in response to ROS levels.     

Regional displacement by sulpiride of [3H]spiperone binding in vivo. Biochemical and behavioural evidence for a preferential action of limbic and nigral dopamine receptors

The regional displacement by sulpiride of [3H]spiperone binding in vivo was studied in the rat. A low dose of sulpiride (20 mg/kg) displaced [3H]spiperone binding in certain limbic regions (olfactory tubercle, septum) and the substantia nigra but not in the nucleus accumbens or striatum. At this does sulpiride preferentially blocked apomorphine induced apomorphine Higher doses of sulpiride (150 and 250 mg/kg), which blocked apomorphine induced stereotypes and induced catalepsy were found to displace [3H]spiperone binding in all regions studied including the striatum and the nucleus accumbens. Haloperidol (0.1 and 1.0 mg/kg) displaced [3H]spiperone to approximately the same extent in all regions studied.     

Role of Gum Chewing on the Duration of Postoperative Ileus Following Ileostomy Closure Done for Typhoid Ileal Perforation: A Prospective Randomized Trial

Background/Aim:

There is ample evidence in the recent literature that gum chewing after elective colonic anastomosis decreases postoperative ileus (POI). But there are very few studies on small bowel anastomosis done in relaparotomy cases. This study aimed to evaluate the effect of gum chewing on the duration of POI following small bowel anastomosis performed for the closure of intestinal stoma, made as temporary diversion in the selected cases of typhoid perforation peritonitis.

Patients and Methods:

Hundred patients undergoing elective small bowel anastomosis for the closure of stoma were randomly assigned to the study group (n=50) and the control group (n=50). The study group patients chewed gum thrice a day for 1 h each time starting 6 h after the surgery until the passage of first flatus. The control group patients had standard postoperative treatment.

Results:

Study and control group patients were comparable at inclusion. The mean time for the appearance of bowel sounds as well as the passage of first flatus was significantly shorter in the study group (P=0.040, P=0.006). The feeling of hunger was also experienced earlier in study group cases (P=0.004). The postoperative hospital stay was shorter in the study group, but the difference was not significant (P=0.059).

Conclusions:

The cases of relaparotomy requiring additional adhesiolysis and small bowel anastomosis for stoma closure are benefited by postoperative gum chewing.