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Background: The utilisation of laparoscopic fundoplication peaked internationally around 2000. Perioperative morbidity, mortality, and length of stay initially declined as the use of laparoscopic technique increased. Studies indicate that complication rates have increased over time, probably as a consequence of rising age and level of comorbidity. None of these previous studies is nationwide. Therefore, this study aimed to investigate trends in the utilisation of anti-reflux surgery in the entire Danish population from 2000 to 2017., Methods: Nationwide Danish health registries were utilised to include all Danish patients undergoing anti-reflux surgery 2000-2017. The utilisation of anti-reflux surgery in procedures per 100.000 inhabitants was compared to the utilisation of proton-pump inhibitors for each year. Postoperative complications, mortality, and length of stay per year, including yearly changes, were also calculated., Results: The use of anti-reflux surgery peaked in 2001 with 5.9 procedures per 100,000 inhabitants and reached its lowest point in 2008 with 2.8 procedures per 100,000 inhabitants. The use of proton-pump inhibitors increased from 3,370 users per 100,000 inhabitants in 2000 to 10,284 users per 100,000 inhabitants in 2017. The 30-day and 90-day mortality ranged from 0 to 1.2%. The 30-day hospital-registered complications were 1.3-6.1%, and the 90-day hospital-registered complications were 2.4-8.3%. Length of stay was consistently low, with a median of 2 days in 2000 reduced to a median of 1 day by 2017., Conclusion: The utilisation of anti-reflux surgery in Denmark from 2000 to 2017 declined, and the use of PPI increased dramatically. Age, comorbidity, and postoperative complications increased, while the use of laparoscopic technique remained high, and mortality was consistently low.

Bisphosphonates are contraindicated in moderate-to-severe chronic kidney disease patients. However, they are used to prevent fragility fractures in patients with impaired kidney function, despite a lack of evidence on their effects on bone density in these patients. We demonstrated that Alendronate had a positive effect on bone in these patients., Purpose: This study aimed to assess the association between alendronate use and bone mineral density (BMD) change in subjects with moderate-severe chronic kidney disease (CKD)., Methods: We created a cohort of CKD stage 3B-5 patients by linking all DXA-based measurements in the Funen area, Denmark, to biochemistry, national health registries and filled prescriptions. Exposure was dispensation of alendronate and the outcome was annualized percentage change in BMD at the femoral neck, total hip and lumbar spine. Individuals were followed from first BMD to the latest of subsequent DXA measurements. Alendronate non-users were identified using incidence density sampling and matched groups were created using propensity scores. Linear regression was used to estimate average differences in the annualized BMD., Results: Use of alendronate was rare in this group of patients: propensity score matching (PSM) resulted in 71 alendronate users and 142 non-users with stage 3B-5 CKD (as in the 1 year before DXA). Whilst alendronate users gained an average 1.07% femoral neck BMD per year, non-users lost an average of 1.59% per annum. The PSM mean differences in annualized BMD were + 2.65% (1.32%, 3.99%), + 3.01% (1.74%, 4.28%) and + 2.12% (0.98%, 3.25%) at the femoral neck, total hip and spine BMD, respectively, all in favour of alendronate users., Conclusion: In a real-world cohort of women with stage 3B-5 CKD, use of alendronate appears associated with a significant improvement of 2-3% per year in the femoral neck, total hip and spine BMD. More data are needed on the anti-fracture effectiveness and safety of bisphosphonate therapy in moderate-severe CKD.

There is strong evidence that peers are of central importance to children's and adolescents' social and emotional adaptation and success in school. However, it remains an open question as to whether callous-unemotional (CU) traits, or interpersonal and affective deficits that pose risk for antisocial behaviors and psychopathy, are related to social-behavioral outcomes as assessed by those who are believed to have the most accurate perspectives on such outcomes - young adolescents' peers. Using data from a longitudinal and multi-method study of peer relations (N = 379, % female = 51.90, M age  = 10.24 at Time 1), the current study addressed this gap by examining the links between teacher-reports of CU traits and conduct problems (CP) and peer-reports of the extent to which young adolescents are aggressive, victimized, excluded, prosocial, and sociable during the Fall and Spring semesters in Grade 5 (Times 1and 2) and Grade 6 (Times 3 and 4). Results revealed that teacher-rated CP, but not CU traits, was associated positively with peer-reports of aggression. CU traits, but not CP, was associated positively with victimization/exclusion and associated negatively with prosociality. CU traits and CP demonstrated opposite relations with sociability, with CU traits demonstrating a negative association. Findings are discussed in the context of the broader literature examining the social-behavioral correlates of CU traits.

In this introduction to the special issue on Social Withdrawal and Anxiety in Childhood and Adolescence: Interaction Between Individual Tendencies and Interpersonal Learning Mechanisms in Development, we analyze conceptual models guiding the twelve studies featured herein. Findings from multiple investigations support Diathesis - Stress Models which emphasize the role of parent- or peer-related interpersonal stress in strengthening affective-behavioral or biological vulnerabilities (diatheses) to anxious solitude or social anxiety. Other investigations support only child vulnerability effects, consistent with a Diathesis-only Model, but such effects are often framed as potentially part of broader Diathesis-Stress or Child by Environment Transactional Models. Next we discuss novelty in development as defined as directional change in the progression of affective-behavioral patterns over time. Novelty in development is postulated in: 1) a Chronic Stress Model that proposes that interpersonal stress can generate or maintain social withdrawal and anxiety; 2) Stress Generation and Transactional Models that propose that child vulnerability can evoke interpersonal stress; and 3) an Ecological Transition Model that proposes that ecological transitions can serve as turning points prompting reorganization in the child-environment system which can result in the deflection of previous patterns of adjustment onto alternate trajectories. We also highlight additional themes from the set of studies found herein. These themes include the significance of gender and culture vis-à-vis the development of social withdrawal and anxiety. Other themes include motivations for social withdrawal; the influence of peer predictability on social withdrawal and brain function; and how the study of multiple developmental pathways has been supported by contemporary analytic techniques.

Behavioral inhibition (BI), a temperament trait characterized by fear and wariness in novel situations, has been identified as a risk factor for later social reticence and avoidance of peer interactions. However, the ability to regulate fearful responses to novelty may disrupt the link between BI and socially reticent behavior. The present study examined how and whether both behaviorally-manifested and physiological indices of emotion regulation moderate the relation between BI and later social reticence. Participants in this study included 88 children followed longitudinally from ages 2 to 4. At age 2, children completed the BI Paradigm in which children's responses to novel objects and adults were observed. At age 4, children's baseline respiratory sinus arrhythmia (RSA) was assessed and mothers reported on children's negative emotionality and soothability. Social reticence at age 4 was observed during a free play session with 3 unfamiliar peers. Results from saturated path models revealed a significant two-way interaction between BI and baseline RSA and a three-way interaction between BI, negative emotionality, and baseline RSA when predicting socially reticent behavior at age 4. At high levels of baseline RSA and high levels of negative emotionality, the association between BI and social reticence was negative. The relation between BI and later social reticence was only positive and significant at low levels of baseline RSA combined with high levels of negative emotionality. The results suggest that either strong physiological regulation or low negative emotionality seems sufficient to buffer inhibited young children against later social reticence.

Callous-unemotional (CU) traits are one meaningful risk factor which helps to explain heterogeneity in the emergence of externalizing behavior problems. While the extant literature demonstrates links between early CU traits and later externalizing problems, there is a dearth of research examining for whom early CU traits confer risk. Data from a longitudinal study (n = 108) were used to examine the extent to which parasympathetic functioning moderated links between CU traits in toddlerhood (m age  = 24.99 months) and externalizing behavior problems at preschool-age (m age  = 51 months). Neither CU traits nor parasympathetic functioning at age 2 directly predicted later externalizing behaviors. However, results show that high levels of CU traits predict elevated externalizing behavior problems, but only for toddlers exhibiting either high baseline respiratory sinus arrhythmia (RSA) or little to no RSA suppression in response to a fear stimulus.

Unlabelled: To evaluate the case-finding strategy for osteoporosis in Norway, a questionnaire concerning risk factors for osteoporosis and history of osteodensitometry was mailed to a population-based cohort of 6000 men and 6000 women. Suboptimal examination rates among high risk and reallocation of scanning capacity to seemingly low-risk individuals was found., Purpose: In Norway, a case-finding strategy for osteoporosis has been used. No data exist regarding the efficacy of this approach. The aim was to examine the prevalence of risk factors for osteoporosis and factors related to the use of dual X-ray absorptiometry (DXA) in Norway., Methods: Questionnaires regarding previous history of DXA, risk factors for osteoporosis and fracture were sent to an age-stratified, nationwide cross-sectional sample of 6000 men and 6000 women aged 40-90 years, drawn from the Norwegian Civil Registration System., Results: Valid responses (6029) were included. Twenty-two point three percent of women and 3.8 % of men had been examined by DXA. Suboptimal examination rates among high risk (e.g., current/previous glucocorticoid treatment or previous low-energy fracture) and reallocation of scanning capacity to seemingly low-risk individuals was found. Of all DXA, 19.5 % were reported by women without any risk factor for osteoporosis, similarly by 16.2 % of men. Distance to DXA facilities and current smoking were inversely related to probability of reporting a DXA., Conclusions: Suboptimal examination rates among high risk and reallocation of scanning capacity to seemingly low-risk individuals were found. Distance to DXA, current smoking, and male sex constituted possible barriers to the case-finding strategy employed. Cheap and more available diagnostic tools for osteoporosis are needed, and risk stratification tools should be employed more extensively.

Unlabelled: Using a Danish Register cohort of 86,039 adult new allopurinol users and propensity score matched controls, we found that gout requiring allopurinol prescription was associated with an increased fracture risk., Purpose: Gout, an acute inflammatory arthritis, is common and associated with elevated serum urate, obesity and high alcohol consumption. The mainstay of therapy is the urate-lowering agent, allopurinol. Here, we report the relationship between allopurinol prescription and fracture in a large registry population., Methods: We established a Danish Register cohort of 86,039 adult cases (new allopurinol users) and 86,039 age, sex and propensity score matched controls (not exposed to allopurinol or with a gout diagnosis), with no diagnosis of malignancy in the year prior., Results: We found a modest adjusted effect of allopurinol prescription on major osteoporotic fractures (hazard ratio (HR) 1.09, 95 % confidence interval (CI) 1.05-1.14, p = 0.04) and on hip fractures (HR 1.07, 95 % CI 1.11-1.14, p < 0.001), robust to adjustment for confounding factors (age, sex, comorbidity, medication use). Associations were stronger in men than women, and among incident allopurinol users whose gout diagnosis had been confirmed by at least one hospital contact. Prespecified subanalyses by filled dose of allopurinol (mg/day in first year of prescription) showed increased hip and major fracture risk in women in the highest allopurinol dose grouping only, while a less strong dose effect was evident for fracture rates in men., Conclusion: Gouty arthritis requiring allopurinol is associated with an excess risk of major or hip fracture, with an allopurinol dose effect evident in women such that women taking the highest doses of allopurinol--suggestive of more severe disease--were at increased risk relative to women taking lower doses.

Behavioral inhibition (BI) and maternal over-control are early risk factors for later childhood internalizing problems, particularly social anxiety disorder (SAD). Consistently high BI across childhood appears to confer risk for the onset of SAD by adolescence. However, no prior studies have prospectively examined observed maternal over-control as a risk factor for adolescent social anxiety (SA) among children initially selected for BI. The present prospective longitudinal study examines the direct and indirect relations between these early risk factors and adolescent SA symptoms and SAD, using a multi-method approach. The sample consisted of 176 participants initially recruited as infants and assessed for temperamental reactivity to novel stimuli at age 4 months. BI was measured via observations and parent-report across multiple assessments between the ages of 14 months and 7 years. Maternal over-control was assessed observationally during parent-child interaction tasks at 7 years. Adolescents (ages 14-17 years) and parents provided independent reports of adolescent SA symptoms. Results indicated that higher maternal over-control at 7 years predicted higher SA symptoms and lifetime rates of SAD during adolescence. Additionally, there was a significant interaction between consistently high BI and maternal over-control, such that patterns of consistently high BI predicted higher adolescent SA symptoms in the presence of high maternal over-control. High BI across childhood was not significantly associated with adolescent SA symptoms when children experienced low maternal over-control. These findings have the potential to inform prevention and early intervention programs by identifying particularly at-risk youth and specific targets of treatment.

Unlabelled: This prospective study investigates the use of phalangeal bone mineral density (BMD) in predicting fractures in a cohort (15,542) who underwent a BMD scan. In both women and men, a decrease in BMD was associated with an increased risk of fracture when adjusted for age and prevalent fractures., Purpose: The aim of this study was to evaluate the ability of a compact and portable scanner using radiographic absorptiometry (RA) to predict major osteoporotic fractures., Methods: This prospective study included a cohort of 15,542 men and women aged 18–95 years, who underwent a BMD scan in Danish Health Examination Survey 2007–2008. BMD at the middle phalanges of the second, third and fourth digits of the non-dominant hand was measured using RA (Alara MetriScan®). These data were merged with information on incident fractures retrieved from the Danish National Patient Registry comprising the International Classification of Diseases (ICD-10). Follow-up was 27–45 months. Major osteoporotic fractures (vertebral fractures, humerus fractures, forearm fractures and hip fractures) were used in the analyses. Fracture events were calculated as "persons with fracture" and evaluated using survival analysis., Results: A total of 307 (1.98 %) of the participants had experienced a new fracture during follow-up. BMD was significantly lower in subjects with fracture (0.32 vs. 0.34 g/cm(2); p < 0.001 adjusted for age, gender, prevalent fractures, height, weight and smoking). In both women and men, a 1 SD decrease in BMD (T score units) was associated with an increased risk of fracture when adjusted for age and prevalent fractures (women: HR = 1.39, CI 1.24–1.54, p < 0.001; men: HR = 1.47, CI 1.20–1.79, p < 0.001)., Conclusion: Phalangeal BMD as measured using RA predicts the incidence of major osteoporotic fractures.

Behavioral inhibition (BI) is characterized by a pattern of extreme social reticence, risk for internalizing behavior problems, and possible protection against externalizing behavior problems. Parenting style may also contribute to these associations between BI and behavior problems (BP). A sample of 113 children was assessed for BI in the laboratory at 14 and 24 months of age, self-report of maternal parenting style at 7 years of age, and maternal report of child internalizing and externalizing BP at 4, 7, and 15 years. Internalizing problems at age 4 were greatest among behaviorally inhibited children who also were exposed to permissive parenting. Furthermore, greater authoritative parenting was associated with less of an increase in internalizing behavior problems over time and greater authoritarian parenting was associated with a steeper decline in externalizing problems. Results highlight the importance of considering child and environmental factors in longitudinal patterns of BP across childhood and adolescence.

Heterogeneity and individual differences in the developmental course of social withdrawal were examined longitudinally in a community sample (N = 392). General Growth Mixture Modeling (GGMM) was used to identify distinct pathways of social withdrawal, differentiate valid subgroup trajectories, and examine factors that predicted change in trajectories within subgroups. Assessments of individual (social withdrawal), interactive (prosocial behavior), relationship (friendship involvement, stability and quality, best friend's withdrawal and exclusion/victimization) and group- (exclusion/victimization) level characteristics were used to define growth trajectories from the final year of elementary school, across the transition to middle school, and then to the final year of middle school (fifth-to-eighth grades). Three distinct trajectory classes were identified: low stable, increasing, and decreasing. Peer exclusion, prosocial behavior, and mutual friendship involvement differentiated class membership. Friendlessness, friendship instability, and exclusion were significant predictors of social withdrawal for the increasing class, whereas lower levels of peer exclusion predicted a decrease in social withdrawal for the decreasing class.

The mutual best friendships of shy/withdrawn and control children were examined for prevalence, stability, best friend's characteristics, and friendship quality. Using peer nominations of shy/socially withdrawn and aggressive behaviors, two groups of children were identified from a normative sample of fifth-grade children: shy/withdrawn (n = 169) and control (nonaggressive/nonwithdrawn; n = 163). Friendship nominations, teacher reports, and friendship quality data were gathered. Results revealed that shy/withdrawn children were as likely as control children to have mutual stable best friendships. Withdrawn children's friends were more withdrawn and victimized than were the control children's best friends; further, similarities in social withdrawal and peer victimization were revealed for withdrawn children and their friends. Withdrawn children and their friends reported lower friendship quality than did control children. Results highlight the importance of both quantitative and qualitative measures of friendship when considering relationships as risk and/or protective factors.

The purpose of this study was to compare mothers of normal, aggressive, and anxious-withdrawn preschoolers with regard to their beliefs about how socially competent behaviors are learned and their beliefs concerning the origins of two types of maladaptive behaviors--aggression and withdrawal. 121 mothers of 4-year olds were questioned about how they think social skills are acquired. They were also presented with descriptions of hypothetical incidents of peer-directed aggression and social withdrawal and asked what they would do about these behaviors, how they would feel about them, and how they would explain them. Children's social behaviors were observed during free play and rated by their teachers. A norm-based multitargeting procedure was used that resulted in the identification of 10 highly aggressive children, 6 highly withdrawn children, and 60 children who were average in social adaptation. Results indicated that mothers of withdrawn children were more likely than mothers of average children to believe that social skills should best be taught in a directive manner and that maladaptive behaviors should be responded to in a high-powered, coercive fashion. These mothers were also more likely than mothers of average children to indicate that they would feel guilty and embarrassed by displays of maladaptive behavior, and they attributed these behaviors to dispositional factors. Mothers of aggressive children suggested highly directive strategies to teach social skills, but were more laissez-faire than mothers of average and withdrawn children in their reactions to maladaptive behaviors.

Behar and Stringfield (1974) have suggested that the Preschool Behavior Questionnaire (PBQ) is a reliable index of young children's social competence. However, there are few extant data in which teacher ratings of children on the PBQ have been correlated with independent assessments of social competence. In this study PBQ ratings of 123 preschoolers were correlated with observations of in-class social and cognitive play behaviors, sociometric status, and social problem-solving skills. Analyses indicated that children rated highly on the PBQ's Anxious-Fearful, Hostile-Aggressive, and Hyperactive-Distractible factors (a) displayed less mature and more aggressive in-class behaviors, (b) were less popular among their peers, and (c) were more likely to suggest negative affect strategies on the social problem-solving measure. Thus, the PBQ appears to be a useful instrument for identifying children with social problems.