A retrospective cross-sectional study on tinnitus prevalence and disease associations in the Dutch population-based cohort Lifelines

Tinnitus is a highly prevalent disorder with heterogenous presentation and limited treatment options. Better understanding of its prevalence and disease and lifestyle risk factor associations in the general population is necessary to identify the underlying mechanisms. To this end, we quantified the preva-lence of tinnitus and identified disease and lifestyle risk factors associated with tinnitus within a gen-eral population cohort. For this study, we used the Lifelines population-based cohort study to perform a retrospective cross-sectional study. Lifelines is a large, multi-generational, prospective cohort study that includes over 167,0 0 0 participants (or 10% of the population) from the northern Netherlands. For this study, conducted between 2018 and 2021, data from the Lifelines population-based cohort study was used to perform a cross-sectional study. Adult participants (age >= 18 years) with data on tinnitus per-ception (collected once between 2011 and 2015) were included in this study. An elastic-net regression analysis was performed with tinnitus as the dependent variable and parameters of diseases and lifestyle risk factors (collected once between 2006 and 2014)-including hearing problems, cardiovascular disease, metabolic disorders, psychiatric disorders, thyroid disease, inflammatory disease, and functional somatic syndromes-as the independent variables. Among 124,609 participants, N = 8,011 (6.4%) reported per-ceiving tinnitus constantly (CT: constant tinnitus) and N = 39,625 (31.8%) reported perceiving tinnitus constantly or occasionally (AT: any tinnitus). Our analysis identified 38 parameters that were associated with AT and 48 parameters that were associated with CT. Our study identified established disease as-sociates with tinnitus, including problems with hearing (OR 8.570 with CT), arrythmia (OR 1.742 with CT), transient ischemic attack (OR 1.284 with AT), diabetes mellitus (OR 1.014 with AT) and psychiatric disorders, including major depressive disorder (OR 1.506 with CT). Factors related to lifestyle associated with tinnitus included waist-hip ratio (OR 1.061 with CT) and smoking (OR 1.028 with AT). Novel disease associates with CT were identified for inflammatory diseases, including rheumatoid arthritis (OR 1.297) and ulcerative colitis (OR 1.588), thyroid disease (as evidenced by the use of thyroid medication) (OR 1.298), and functional somatic syndromes, including chronic fatigue syndrome (OR 1.568). In addition to validating established disease associates in a general population cohort, this study identified novel associ-ations with tinnitus and several disease categories, including functional somatic syndromes, inflammatory diseases, and thyroid disease. Future work will be necessary to identify whether (common) mechanisms underly tinnitus and these associated disorders. Lifelines is an important new resource available for future studies investigating tinnitus in the general population. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/

Longitudinal relations between autistic-like features and functional somatic symptoms in adolescence

Autistic-like features and functional somatic symptoms (FSS) frequently co-occur. It remains unknown how autistic-like features and FSS affect each other and develop throughout adolescence. This study examined reciprocal relations between autistic-like features and FSS in adolescence. Participants were 2772 adolescents (52.5% male) from the Tracking Adolescents’ Individual Lives Survey population and clinical cohort. Data from four waves were included, covering the ages between 11 and 19 years. Autistic-like features were measured using the Children’s Social Behavior Questionnaire. FSS were assessed using the Youth Self Report and Adult Self Report, respectively. Using the random intercept cross-lagged panel model, a stable positive, moderately strong between-persons association was found between autistic-like features and FSS. No within-persons reciprocal effects from wave to wave were observed. Secondary analyses revealed a consistent relation with FSS for three different domains of autistic-like features (social and communication behaviors, repetitive behaviors, and self-regulatory behaviors), and highly similar interrelations in a subsample of adolescents with a clinical autism spectrum disorder diagnosis. In conclusion, the co-occurrence between autistic-like features and FSS is stable throughout adolescence. Clinicians working with adolescents with autistic-like features should be alert to the presence FSS, and vice versa

Discordance between Adolescents and Parents in Functional Somatic Symptom Reports:Sex Differences and Future Symptom Prevalence

Functional somatic symptoms, i.e., physical complaints that cannot be sufficiently explained by an objectifiable biomedical abnormality, become increasingly more prevalent in girls than in boys during adolescence. Both parents and adolescents report more functional somatic symptoms in girls, but their reports correspond only limitedly. It remains unknown whether parent-adolescent discordance contributes to the higher symptom prevalence in girls. This study investigated parent-adolescent discordance in reported functional somatic symptoms throughout adolescence, examined the longitudinal association of parent-adolescent discordance with symptom prevalence in early adulthood and focused on sex differences in these processes. Participants included 2229 adolescents (50.7% female) from four assessments (age 11 to 22 years) of the TRAILS population cohort. Parents and adolescents reported significantly more symptoms in girls than in boys during adolescence. Variance analyses showed that throughout adolescence, parents reported fewer symptoms than girls self-reported and more than boys self-reported. Regression analyses using standardized difference scores showed that lower parent-report than self-report was positively associated with symptom prevalence in early adulthood. Polynomial regression analyses revealed no significant interaction between parent-reported and adolescent self-reported symptoms. Associations did not differ between boys and girls. The findings show that lower parent-reported than self-reported symptoms predict future symptom prevalence in both sexes, but this discordance was more observed in girls. The higher functional somatic symptom prevalence in girls might be partly explained by parental underestimation of symptoms.</p

How does the general public balance convenience and cognitive pharmaceutical services in community pharmacy practice

Background: Community pharmacy is shifting its focus from traditional, product-focused roles to the provision of cognitive pharmaceutical services (CPS). Previous research has indicated that community pharmacists predominantly want to devote their capacity to CPS. Ideally, services provided also address users' needs. The general public's preferences regarding the services provided by community pharmacists are currently less understood. Aim: This study investigates the general public's preferences and perceived importance of CPS versus convenience in community pharmacy practice. Method: An online survey of 1.500 members of the Dutch Health Care Consumer Panel containing questions regarding preferences for CPS and convenience was distributed. Descriptive statistics and linear regression analysis were performed to investigate the relationship between preferences and participant characteristics. Results: 516 panel members completed all questions regarding preferences and importance of the availability of services. The majority preferred convenience (68.2%) and a smaller proportion preferred CPS (27.7%). However, participants considered it important from a societal viewpoint that CPS is provided (45.0%). Participants who preferred CPS over convenience were generally older (p < 0.001) and used more medicines (p < 0.001). Conclusion: Convenience of community pharmacy services is most preferred by the general public. However, CPS is perceived as important, especially for elderly who use more medicines. Elderly patients who use more medicines more often rate CPS as more important than convenience. These findings suggest that community pharmacists should ensure that pharmacy logistics are organized efficiently before focusing on the provision of CPS

Two-year effectiveness of a stepped-care depression prevention intervention and predictors of incident depression in primary care patients with diabetes type 2 and/or coronary heart disease and subthreshold depression; data from the Step-Dep cluster randomized controlled trial

Introduction Major depressive disorders (MDD), diabetes mellitus type 2 (DM2) and coronary heart disease (CHD) are leading contributors to the global burden of disease and often co-occur. Objectives To evaluate the two-year effectiveness of a stepped-care intervention to prevent MDD compared to usual care and to develop a prediction model for incident depression in DM2 and/or CHD patients with subthreshold depression. Methods Data of 236 Dutch primary care DM2/CHD patients with subthreshold depression (Patient Health Questionnaire 9 (PHQ-9) score ≥6, no current MDD according to the Mini International Neuropsychiatric Interview (DSM-IV criteria)), who participated in the Step-Dep trial were used. A PHQ-9 score of ≥10 at minimally one measurement during follow-up (at 3, 6, 9, 12 and 24 months) was used to determine the cumulative incidence of MDD. Potential demographic and psychological predictors were measured at baseline via web-based self-reported questionnaires and evaluated using a multivariable logistic regression model. Model performance was assessed with the Hosmer–Lemeshow test, Nagelkerke’s R2 explained variance and Area Under the Receiver Operating Characteristic curve (AUC). Bootstrapping techniques were used to internally validate our model. Results 192 patients (81%) were available at two-year follow-up. The cumulative incidence of MDD was 97/192 (51%). There was no statistically significant overall treatment effect over 24 months of the intervention (OR 1.37; 95% CI 0.52; 3.55). Baseline levels of anxiety, depression, the presence of >3 chronic diseases and stressful life-events predicted the incidence of MDD (AUC 0.80 interquartile range (IQR) 0.79-0.80; Nagelkerke’s R2 0.34 IQR 0.33-0.36). Conclusion A model with four factors predicted depression incidence during two-year follow-up in patients with DM2/CHD accurately, based on the AUC. The Step-Dep intervention did not influence the incidence of MDD. Future depression prevention programs should target patients with these four predictors present, and aim to reduce both anxiety and depressive symptoms

Quality improvement intervention to stimulate early mobilization of critically ill children

Background: Immobility during hospital stay is associated with muscle weakness, delirium, and delayed neurocognitive recovery. Early mobilization of critically ill adults improves their physical functioning and shortens the duration of mechanical ventilation. However, comparable research in children is lacking. Aims: To determine the effects of the implementation of an early mobilization (EM) program on mobility activities for critically ill children and to explore barriers and facilitators and clinical outcomes before and after implementation. Study design: A prospective single-centre before-and-after study. Methods: This study was conducted in a PICU of a large tertiary hospital. Children aged from 3 months to 18 years, with an expected stay of ≥3 days were eligible to participate. In the “before” phase, participants received usual care; in the “after” phase we implemented a multicomponent, multidisciplinary EM protocol. The primary outcome was a change in the process outcome “mobilization activities”. Secondary outcomes were PICU staff opinions on mobilization (survey), safety, process measures, involvement of parents and physical therapist, and clinical outcomes (sedative use and prevalence of delirium). Results: A total of 113 children were included; 55 before and 58 after, with a median age of 31 months (IQR: 10–103) and 35 months (IQR: 7–152), respectively. The number of mobilization activities (per patient per day) had significantly increased from 5 (IQR: 2–7) to 6 (IQR: 4–8) (U = 272185.0; p &lt;.001). PT consultations for mobilization had significantly increased from 23.6% (13/55) to 46.5% (27/58) (X2 = 6.48; p =.011). In both phases, no mobilization-related adverse events were documented. The survey showed that PICU staff found EM of critically ill children useful and feasible. In the after phase, PICU staff rated the perceived benefit of the support of the physical therapist during mobilization activities significantly higher than in the before phase (X2 = 34.80; p &lt;.001). Conclusions: Implementation of a structured EM program for critically ill children is feasible and safe. Relevance to clinical practice: It is suggested to start the implementation of a structed EM program with the idendentification of local barriers and facilitators by an interdisciplinary PICU team. Further, an increased presence of physiotherapists on the PICU would improve mobilisation levels, and facilitate mobilisation in critically ill children. Also, they can support and advice PICU nurses and parents in mobilising children.</p

Pre- and post-Golgi translocation of glucosylceramide in glycosphingolipid synthesis

Glycosphingolipids are controlled by the spatial organization of their metabolism and by transport specificity. Using immunoelectron microscopy, we localize to the Golgi stack the glycosyltransferases that produce glucosylceramide (GlcCer), lactosylceramide (LacCer), and GM3. GlcCer is synthesized on the cytosolic side and must translocate across to the Golgi lumen for LacCer synthesis. However, only very little natural GlcCer translocates across the Golgi in vitro. As GlcCer reaches the cell surface when Golgi vesicular trafficking is inhibited, it must translocate across a post-Golgi membrane. Concanamycin, a vacuolar proton pump inhibitor, blocks translocation independently of multidrug transporters that are known to translocate short-chain GlcCer. Concanamycin did not reduce LacCer and GM3 synthesis. Thus, GlcCer destined for glycolipid synthesis follows a different pathway and transports back into the endoplasmic reticulum (ER) via the late Golgi protein FAPP2. FAPP2 knockdown strongly reduces GM3 synthesis. Overall, we show that newly synthesized GlcCer enters two pathways: one toward the noncytosolic surface of a post-Golgi membrane and one via the ER toward the Golgi lumen LacCer synthase

The influence of intensive care treatment in infancy on cortisol levels in childhood and adolescence

Background: Infants admitted to the intensive care unit experience numerous early-life stressors, which may have long-term effects on hypothalamic-pituitary-adrenal axis functioning. Aims: To determine the effects of intensive care treatment and related exposure to stress, pain, and opioids in infancy on cortisol levels in childhood and adolescence. Study design: Cross-sectional study. Subjects: Children and adolescents aged 8 to 18 years with a history of intensive care treatment in infancy and healthy controls. The intensive care treatment cohort consisted of four subgroups with varying levels of exposure to stress, pain, and opioids in infancy. They received either mechanical ventilation, extracorporeal membrane oxygenation, major surgery, or excochleation of a giant congenital melanocytic nevus. Outcome measures: Between-group differences in stress reactivity to a study visit consisting of pain threshold testing and an MRI examination and diurnal cortisol levels, as measured in saliva. Results: After adjustment for age, sex, and gestational age, the diurnal cortisol output (AUCg) in the overall intensive care group (N = 76) was 18 % (approximately 1000 nmol/L) (95 % CI [−31 %, −3 %], P = 0.022) lower than that in the control group (N = 67). Cortisol awakening response, diurnal decline, and stress reactivity neither differed significantly between the overall intensive care group and control group, nor between the intensive care subgroups and control group. Conclusion: Children and adolescents with a history of intensive care treatment in infancy have similar cortisol profiles to those of healthy controls, except for an 18 % lower diurnal cortisol output. The clinical relevance of this reduction is yet to be determined.</p