Socio-demographic variation in diagnosis of and prescribing for common mental illnesses among children and young people during the COVID-19 pandemic: time series analysis of primary care electronic health records.

BACKGROUND: The impact of the COVID-19 pandemic on the mental health of children and young people (CYP) has been widely reported. Primary care electronic health records were utilised to examine trends in the diagnosing, recording and treating of these common mental disorders by ethnicity and social deprivation in Greater Manchester, England. METHODS: Time-series analyses conducted using Greater Manchester Care Record (GMCR) data examined all diagnosed episodes of anxiety disorders and depression and prescribing of anxiolytics and antidepressants among patients aged 6-24 years. The 41-month observation period was split into three epochs: Pre-pandemic (1/2019-2/2020); Pandemic Phase 1 (3/2020-6/2021); Pandemic Phase 2 (7/2021-5/2022). Rate ratios for all CYP specific to sex, age, ethnicity, and neighbourhood-level Indices of Multiple Deprivation (IMD) quintile were modelled using negative binomial regression. RESULTS: Depression and anxiety disorder rates were highest in females, CYP aged 19-24, and White and 'Other' ethnic groups. During Pandemic Phase 1, rates for these diagnoses fell in all demographic subgroups and then rose to similar levels as those recorded pre-pandemic. In Pandemic Phase 2, rates in Black and Mixed-ethnicity females rose to a significantly greater degree (by 54% and 62%, respectively) than those in White females. Prescribing rates increased throughout the study period, with significantly greater rises observed in non-White females and males. The temporal trends were mostly homogeneous across deprivation quintiles. CONCLUSION: The observed fluctuations in frequency of recorded common mental illness diagnoses likely reflect service accessibility and patients' differential propensities to consult as well as changing levels of distress and psychopathology in the population. However, psychotropic medication prescribing increased throughout the observation period, possibly indicating a sustained decline in mental health among CYP, and also clinicians' responses to problems presented. The comparatively greater increases in frequencies of diagnosis recording and medication prescribing among ethnic minority groups warrants further investigation.

Bibliometric and trend analysis of the top 100 most-cited articles on lateral interbody fusion (LIF).

PURPOSE: Lateral interbody fusion (LIF) is an increasingly popular minimally-invasive spine procedure. This study identifies notable trends in LIF literature and provides a detailed review of the bibliometric aspects of the top 100 most-cited articles. METHODS: Articles were queried from the Web of Science database. Inclusion criteria consisted of peer-reviewed articles, full-text availability, and LIF focus. Network analysis including co-authorship mapping and bibliographic coupling were complemented by trend analysis to determine prominent contributors and themes. Analyses were conducted using VOSviewer and Bibliometrix (RStudio). RESULTS: There has been a rapid increase in LIF publication and citation count since 1998. Leading journals were Spine (n = 24), Journal of Neurosurgery Spine (n = 22), and European Spine Journal (n = 12). NuVasive funded the most publications (n = 17), followed by DePuy Synthes Spine (n = 4). The United States was the most represented country (n = 81); however, trend analysis suggests a steadily growing international contribution. The most prolific author was J.S. Uribe (n = 16), followed by a tie in second place by E. Dakwar and L. Pimenta (n = 8). The most frequent keywords, "complication" (n = 34), "surgery" (n = 30), and "outcomes" (n = 24), demonstrated a patient-centric theme. CONCLUSIONS: This bibliometric analysis provides in-depth insights into the evolution and trends of LIF over the last two decades. The trends and themes identified demonstrate the innovative, collaborative, and patient-focused characteristics of this subfield. Future researchers can use this as a foundation for understanding the past and present state of LIF research while designing investigations.

Machine learning models on a web application to predict short-term postoperative outcomes following anterior cervical discectomy and fusion.

BACKGROUND: The frequency of anterior cervical discectomy and fusion (ACDF) has increased up to 400% since 2011, underscoring the need to preoperatively anticipate adverse postoperative outcomes given the procedure's expanding use. Our study aims to accomplish two goals: firstly, to develop a suite of explainable machine learning (ML) models capable of predicting adverse postoperative outcomes following ACDF surgery, and secondly, to embed these models in a user-friendly web application, demonstrating their potential utility. METHODS: We utilized data from the National Surgical Quality Improvement Program database to identify patients who underwent ACDF surgery. The outcomes of interest were four short-term postoperative adverse outcomes: prolonged length of stay (LOS), non-home discharges, 30-day readmissions, and major complications. We utilized five ML algorithms - TabPFN, TabNET, XGBoost, LightGBM, and Random Forest - coupled with the Optuna optimization library for hyperparameter tuning. To bolster the interpretability of our models, we employed SHapley Additive exPlanations (SHAP) for evaluating predictor variables' relative importance and used partial dependence plots to illustrate the impact of individual variables on the predictions generated by our top-performing models. We visualized model performance using receiver operating characteristic (ROC) curves and precision-recall curves (PRC). Quantitative metrics calculated were the area under the ROC curve (AUROC), balanced accuracy, weighted area under the PRC (AUPRC), weighted precision, and weighted recall. Models with the highest AUROC values were selected for inclusion in a web application. RESULTS: The analysis included 57,760 patients for prolonged LOS [11.1% with prolonged LOS], 57,780 for non-home discharges [3.3% non-home discharges], 57,790 for 30-day readmissions [2.9% readmitted], and 57,800 for major complications [1.4% with major complications]. The top-performing models, which were the ones built with the Random Forest algorithm, yielded mean AUROCs of 0.776, 0.846, 0.775, and 0.747 for predicting prolonged LOS, non-home discharges, readmissions, and complications, respectively. CONCLUSIONS: Our study employs advanced ML methodologies to enhance the prediction of adverse postoperative outcomes following ACDF. We designed an accessible web application to integrate these models into clinical practice. Our findings affirm that ML tools serve as vital supplements in risk stratification, facilitating the prediction of diverse outcomes and enhancing patient counseling for ACDF.

The association of herpes zoster and influenza vaccinations with the risk of developing dementia: a population-based cohort study within the UK Clinical Practice Research Datalink.

BACKGROUND: Dementia affects ability to remember, think, or make decisions that interfere with doing everyday activities. There is no cure, therefore any prevention or delay of the onset is of importance. This study aims to investigate the association between zoster and influenza vaccinations and the risk of developing dementia. METHODS: We conducted a retrospective population-based cohort study using electronic health records from 1469 general practices contributing to the Clinical Practice Research Datalink (CPRD) Aurum database with linked hospital episode statistics (HES) and Office for National Statistics (ONS) mortality records. We built two 'matched cohorts': zoster vaccine (854,745 exposed individuals) matched with 8.8 million comparators without a history of zoster vaccination, and influenza vaccine (742,487 exposed individuals) matched with 7.12 million comparators without a history of vaccination as another comparator group. The cohorts were then followed to assess the association of exposure (vaccine) with outcome (dementia diagnosis). RESULTS: Zoster vaccination was associated with a lower risk of dementia diagnosis (adjusted hazard ratio (HR) 0.78 with 95% CI: 0.77-0.79), Alzheimer's diagnosis (adjusted HR 0.91 with 95% CI: 0.89-0.92 and other types of dementia (adjusted HR 0.71 with 95% CI: 0.69-0.72). Influenza vaccination also was associated with a slightly reduced hazard of dementia risk (adjusted HR 0.96 with 95% CI: 0.94-0.97). CONCLUSION: Both zoster vaccine for prevention of shingles / herpes zoster and influenza vaccine to prevent influenza were associated with diminished risk of dementia, with the zoster association appearing more pronounced.

Incidence of nonvalvular atrial fibrillation and oral anticoagulant prescribing in England, 2009 to 2019: A cohort study.

BACKGROUND: Atrial fibrillation (AF) is an important risk factor for ischaemic stroke, and AF incidence is expected to increase. Guidelines recommend using oral anticoagulants (OACs) to prevent the development of stroke. However, studies have reported the frequent underuse of OACs in AF patients. The objective of this study is to describe nonvalvular atrial fibrillation (NVAF) incidence in England and assess the clinical and socioeconomic factors associated with the underprescribing of OACs. METHODS AND FINDINGS: We conducted a population-based retrospective cohort study using the UK Clinical Practice Research Datalink (CPRD) database to identify patients with NVAF aged ≥18 years and registered in English general practices between 2009 and 2019. Annual incidence rate of NVAF by age, deprivation quintile, and region was estimated. OAC prescribing status was explored for patients at risk for stroke and classified into the following: OAC, aspirin only, or no treatment. We used a multivariable multinomial logistic regression model to estimate relative risk ratios (RRRs) and 95% confidence intervals (CIs) of the factors associated with OAC or aspirin-only prescribing compared to no treatment in patients with NVAF who are recommended to take OAC. The multivariable regression was adjusted for age, sex, comorbidities, socioeconomic status, baseline treatment, frailty, bleeding risk factors, and takes into account clustering by general practice. Between 2009 and 2019, 12,517,191 patients met the criteria for being at risk of developing NVAF. After a median follow-up of 4.6 years, 192,265 patients had an incident NVAF contributing a total of 647,876 person-years (PYR) of follow-up. The overall age-adjusted incidence of NVAF per 10,000 PYR increased from 20.8 (95% CI: 20.4; 21.1) in 2009 to 25.5 (25.1; 25.9) in 2019. Higher incidence rates were observed for older ages and males. Among NVAF patients eligible for anticoagulation, OAC prescribing rose from 59.8% (95% CI: 59.0; 60.6) in 2009 to 83.2% (95% CI: 83.0; 83.4) in 2019. Several conditions were associated with lower risk of OAC prescribing: dementia [RRR 0.52 (0.47; 0.59)], liver disease 0.58 (0.50; 0.67), malignancy 0.74 (0.72; 0.77), and history of falls 0.82 (0.78; 0.85). Compared to white ethnicity, patients from black and other ethnic minorities were less likely to receive OAC; 0.78 (0.65; 0.94) and 0.76 (0.64; 0.91), respectively. Patients living in the most deprived areas were less likely to receive OAC 0.85 (0.79; 0.91) than patients living in the least deprived areas. Practices located in the East of England were associated with higher risk of prescribing aspirin only over no treatment than practices in London (RRR 1.22; 95% CI 1.02 to 1.45). The main limitation of this study is that these findings depends on accurate recording of conditions by health professionals and the inevitable residual confounding due to lack of data on certain factors that could be associated with under-prescribing of OACs. CONCLUSIONS: The incidence of NVAF increased between 2009 and 2015, before plateauing. Underprescribing of OACs in NVAF is associated with a range of comorbidities, ethnicity, and socioeconomic factors, demonstrating the need for initiatives to reduce inequalities in the care for AF patients.

Suicide and other causes of death among working-age and older adults in the year after discharge from in-patient mental healthcare in England: matched cohort study.

BACKGROUND: Evidence for risk of dying by suicide and other causes following discharge from in-patient psychiatric care throughout adulthood is sparse. AIMS: To estimate risks of all-cause mortality, natural and external-cause deaths, suicide and accidental, alcohol-specific and drug-related deaths in working-age and older adults within a year post-discharge. METHOD: Using interlinked general practice, hospital, and mortality records in the Clinical Practice Research Datalink we delineated a cohort of discharged adults in England, 2001-2018. Each patient was matched to up to 20 general population comparator patients. Cumulative incidence (absolute risks) and hazard ratios (relative risks) were estimated separately for ages 18-64 and ≥65 years with additional stratification by gender and practice-level deprivation. RESULTS: The 1-year cumulative incidence of dying post-discharge was 2.1% among working-age adults (95% CI 2.0-2.3) and 14.1% (95% CI 13.6-14.5) among older adults. Suicide risk was particularly elevated in the first 3 months, with hazard ratios of 191.1 (95% CI 125.0-292.0) among working-age adults and 125.4 (95% CI 52.6-298.9) in older adults. Older patients were vulnerable to dying by natural causes within 3 months post-discharge. Risk of dying by external causes was greater among discharged working-age adults in the least deprived areas. Relative risk of suicide in discharged working-age women relative to their general population peers was double the equivalent male risk elevation. CONCLUSIONS: Recently discharged adults at any age are at increased risk of dying from external and natural causes, indicating the importance of close monitoring and provision of optimal support to all such patients, particularly during the first 3 months post-discharge.

Risk factors for nonfatal self-harm and suicide among adolescents: two nested case-control studies conducted in the UK Clinical Practice Research Datalink.

BACKGROUND: The characteristics of adolescents who die by suicide have hitherto been examined in uncontrolled study designs, thereby precluding examination of risk factors. The degree to which antecedents of nonfatal self-harm and suicide at young age differ remains unknown. METHOD: We delineated two nested case-control studies of patients aged 10-19 years using the Clinical Practice Research Datalink with interlinked hospital and national mortality records. Cases were adolescents who between 1st January 2003 and 31st December 2018 had died from suicide (N = 324) - study 1; experienced their first self-harm episode (N = 56,008) - study 2. In both studies, cases were matched on sex, age and practice-level deprivation quintile to 25 controls. By fitting conditional logistic regression, we examined how risks varied according to psychiatric diagnoses, prescribed psychotropic medication, patterns of clinical contact and area-level deprivation. RESULTS: Suicides occurred more often among boys (66%), but self-harm was more common in girls (68%). Most individuals who self-harmed or died from suicide presented to their GP at least once in the preceding year (85% and 75% respectively). Only a third of cases had one of the examined diagnostic categories recorded. Depression was most strongly associated with elevated risks for both outcomes (self-harm: OR 7.9; 95% CI 7.8-8.2; suicide: OR 7.4; 95% CI 5.5-9.9). Except for autism spectrum disorder, all other diagnostic categories were linked with similar risk elevations for self-harm as for suicide. Whilst self-harm risk rose incrementally with increasing levels of area-level deprivation, suicide risks did not. CONCLUSIONS: We observed few marked differences in risk factor profiles for nonfatal self-harm versus suicide. As most adolescents who had harmed themselves or died by suicide were known to services in the preceding year, their underlying pathology may not be adequately identified and treated. Our findings highlight the need for a multiagency approach to treatment and prevention.

The Macrotextured Implant Recall: Breast Implant-Associated-Anaplastic Large Cell Lymphoma Risk Aversion in Cosmetic and Reconstructive Plastic Surgery Practices.

BACKGROUND: The recall of Allergan Biocell (Irvine, CA) devices due to the association between anaplastic large cell lymphoma (ALCL) and macrotextured breast implants means that plastic surgeons are faced with the challenge of caring for patients with these implants in situ. Cosmetic and reconstructive surgeons have been contacting affected patients to encourage them to follow up and discuss the most appropriate risk-reduction strategies. OBJECTIVES: The aim of this study was to evaluate patient concerns about the risk of breast implant-associated ALCL (BIA-ALCL) and to compare management differences between cosmetic and reconstructive patients. METHODS: A retrospective review was performed of 432 patients with macrotextured implants who presented to clinic after being contacted (121 reconstructive and 311 cosmetic). These records were analyzed for their presenting concerns, surgery wait times, and management plans. Statistical analysis was performed to compare the cohorts, and odds ratios (ORs) were computed to determine the association between patient concerns and their choice of management. RESULTS: After consultation, 59.5% of the reconstructive cohort and 49.5% of the cosmetic cohort scheduled implant removal or exchange. The reconstructive population had a higher rate of ALCL concern (62.7%); however, both cohorts had a significant OR, demonstrating an expressed fear of ALCL likely contributed to their subsequent clinical management (OR cosmetic, 1.66; OR reconstructive, 2.17). CONCLUSIONS: Although the risk of ALCL appears to be more concerning to the reconstructive population, both cohorts were equally motivated to have their implants removed. Informing patients about their ALCL risk is crucial to ensure a patient-supported risk reduction plan.

Thromboembolic Events in Users of Warfarin Treated with Different Skeletal Muscle Relaxants.

Background and Objectives: Warfarin and a skeletal muscle relaxant are co-treatments in nearly a quarter-million annual United States (US) office visits. Despite international calls to minimize patient harm arising from anticoagulant drug interactions, scant data exist on clinical outcomes in real-world populations. We examined effects of concomitant use of warfarin and individual muscle relaxants on rates of hospitalization for thromboembolism among economically disadvantaged persons. Materials and Methods: Using 1999−2012 administrative data of four US state Medicaid programs, we conducted 16 retrospective self-controlled case series studies: half included concomitant users of warfarin + one of eight muscle relaxants; half included concomitant users of an inhaled corticosteroid (ICS) + one of eight muscle relaxants. The ICS analyses served as negative control comparisons. In each study, we calculated incidence rate ratios (IRRs) comparing thromboembolism rates in the co-exposed versus warfarin/ICS-only exposed person-time, adjusting for time-varying confounders. Results: Among ~70 million persons, we identified 8693 warfarin-treated subjects who concomitantly used a muscle relaxant, were hospitalized for thromboembolism, and met all other inclusion criteria. Time-varying confounder-adjusted IRRs ranged from 0.31 (95% confidence interval: 0.13−0.77) for metaxalone to 3.44 (95% confidence interval: 1.53−7.78) for tizanidine. The tizanidine finding was robust after quantitatively adjusting for negative control ICS findings, and in numerous prespecified secondary analyses. Conclusions: We identified a potential >3-fold increase in the rate of hospitalized thromboembolism in concomitant users of warfarin + tizanidine vs. warfarin alone. Alternative explanations for this finding include confounding by indication, a native effect of tizanidine, or chance.

Isolated Intracranial Hemorrhage in Elderly Patients With Pre-Injury Anticoagulation: Is Full Trauma Team Activation Necessary?

BACKGROUND: Traumatic intracranial hemorrhage (ICH) is a highly morbid injury, particularly among elderly patients on preinjury anticoagulants (AC). Many trauma centers initiate full trauma team activation (FTTA) for these high-risk patients. We sought to determine if FTTA was superior compared with those who were evaluated as a trauma consultation (CON). METHODS: Patients aged ≥55 on preinjury AC who presented from January 2015 to December 2019 with blunt isolated head injury (non-head AIS ≤2) and confirmed ICH were identified. CON patients and FTTA patients were matched by age and head AIS. Cox proportional hazard model was used to assess patient and injury characteristics with mortality and survivor discharge disposition. REASULTS: There were 45 CON patients and 45 FTTA patients. Mean age was 80 years in both groups. Fall was the most common mechanism (98% CON vs. 92% FTTA). Glasgow Coma Score (GCS) was lower in FTTA (14 vs. 15, p<0.01). CON had a significantly longer time from arrival to CT scan (1.3 vs. 0.4 hrs, p<0.01). Hospital days were similar (CON: 3.9 vs. FTTA: 3.7 days). However, CON had increased ventilator use (p=0.03). Lower admission GCS was the only factor associated with increased risk of death. Among survivors, only head AIS increased the risk of discharge to a level of care higher than that of preinjury (p=0.01). CONCLUSION: There was no difference in mortality or adverse discharge disposition between FTTA and CON, although FTTA was associated with a more rapid evaluation and diagnosis. Any alteration in GCS was strongly associated with mortality and should prompt evaluation by FTTA.

Temporal trends in annual incidence rates for psychiatric disorders and self-harm among children and adolescents in the UK, 2003-2018.

BACKGROUND: There has been growing concern in the UK over recent years that a perceived mental health crisis is affecting children and adolescents, although published epidemiological evidence is limited. METHODS: Two population-based UK primary care cohorts were delineated in the Aurum and GOLD datasets of the Clinical Practice Research Datalink (CPRD). We included data from 9,133,246 individuals aged 1-20 who contributed 117,682,651 person-years of observation time. Sex- and age-stratified annual incidence rates were estimated for attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) (age groups: 1-5, 6-9, 10-12, 13-16, 17-19), depression, anxiety disorders (6-9, 10-12, 13-16, 17-19), eating disorders and self-harm (10-12, 13-16, 17-19) during 2003-2018. We fitted negative binomial regressions to estimate incidence rate ratios (IRRs) to examine change in incidence between the first (2003) and final year (2018) year of observation and to examine sex-specific incidence. RESULTS: The results indicated that the overall incidence has increased substantially in both boys and girls in between 2003 and 2018 for anxiety disorders (IRR 3.51 95% CI 3.18-3.89), depression (2.37; 2.03-2.77), ASD (2.36; 1.72-3.26), ADHD (2.3; 1.73-3.25), and self-harm (2.25; 1.82-2.79). The incidence for eating disorders also increased (IRR 1.3 95% CI 1.06-1.61), but less sharply. The incidence of anxiety disorders, depression, self-harm and eating disorders was in absolute terms higher in girls, whereas the opposite was true for the incidence of ADHD and ASD, which were higher among boys. The largest relative increases in incidence were observed for neurodevelopmental disorders, particularly among girls diagnosed with ADHD or ASD. However, in absolute terms, the incidence was much higher for depression and anxiety disorders. CONCLUSION: The number of young people seeking help for psychological distress appears to have increased in recent years. Changes to diagnostic criteria, reduced stigma, and increased awareness may partly explain our results, but we cannot rule out true increases in incidence occurring in the population. Whatever the explanation, the marked rise in demand for healthcare services means that it may be more challenging for affected young people to promptly access the care and support that they need.

IKKε and TBK1 in diffuse large B-cell lymphoma: A possible mechanism of action of an IKKε/TBK1 inhibitor to repress NF-κB and IL-10 signalling.

The IKK-related kinases, IKKε and TBK1, have essential roles in innate immunity in part through modifying MYD88 signalling from the Toll-like receptors to regulate NF-κB signalling. We investigated the expression and function of IKKε and TBK1, in diffuse large B-cell lymphoma (DLBCL). DLBCL cell lines and patient-derived xenografts were used to determine their sensitivity to IKKε and TBK1 inhibitors. To understand the function of IKKε and TBK1 secreted factors were determined following administration of inhibitors. Gene expression microarrays were used to determine the transcriptional effects of inhibitors. Higher TBK1 mRNA levels associated with poorer clinical outcome but IKKε and TBK1 were expressed in both germinal centre and non-germinal centre types of DLBCL. Survival of cell lines Ly10, Ly03 and Pfeiffer, and of some primary human lymphoma cells, was suppressed by a small molecule IKKε/TBK1 inhibitor, DMX3433. DMX3433 reduced IL-10 production from Ly10 and repressed NF-κB mediated transcription. Inhibition of IKKε and TBK1 warrants further investigation as a potential therapeutic route to suppress NF-κB signalling in lymphoma.

Prevalence of comorbid mental and physical illnesses and risks for self-harm and premature death among primary care patients diagnosed with fatigue syndromes.

BACKGROUND: Fatigue syndromes (FSs) affect large numbers of individuals, yet evidence from epidemiological studies on adverse outcomes, such as premature death, is limited. METHODS: Cohort study involving 385 general practices in England that contributed to the Clinical Practice Research Datalink (CPRD) with linked inpatient Hospital Episode Statistics (HES) and Office for National Statistics (ONS) cause of death information. A total of 10 477 patients aged 15 years and above, diagnosed with a FS during 2000-2014, were individually matched with up to 20 comparator patients without a history of having a FS. Prevalence ratios (PRs) were estimated to compare the FS and comparison cohorts on clinical characteristics. Adjusted hazard ratios (HRs) for subsequent adverse outcomes were estimated from stratified Cox regression models. RESULTS: Among patients diagnosed with FSs, we found elevated baseline prevalence of: any psychiatric illness (PR 1.77; 95% CI 1.72-1.82), anxiety disorders (PR 1.92; 1.85-1.99), depression (PR 1.89; 1.83-1.96), psychotropic prescriptions (PR 1.68; 1.64-1.72) and comorbid physical illness (PR 1.28; 1.23-1.32). We found no significant differences in risks for: all-cause mortality (HR 0.99; 0.91-1.09), natural death (HR 0.99; 0.90-1.09), unnatural death (HR 1.00; 0.59-1.72) or suicide (HR 1.68; 0.78-3.63). We did, however, observe a significantly elevated non-fatal self-harm risk: HR 1.83; 1.56-2.15. CONCLUSIONS: The absence of elevated premature mortality risk is reassuring. The raised prevalence of mental illness and increased non-fatal self-harm risk indicate a need for enhanced assessment and management of psychopathology associated with fatigue syndromes.

Temporal trends in incidence of hospital-treated self-harm among adolescents in Denmark: national register-based study.

BACKGROUND: Studies conducted in the UK and in Ireland have reported increased rates of self-harm in adolescent females from around the time of the 2008 economic recession and through periods of subsequent national austerity programme implementation. It is not known if incidence rates have increased similarly in other Western European countries during this period. METHODS: Data from interlinked national administrative registers were extracted for individuals born in Denmark during 1981-2006. We estimated gender- and age-specific incidence rates (IRs) per 10,000 person-years at risk for hospital-treated non-fatal self-harm during 2000-2016 at ages 10-19 years. RESULTS: Incidence of self-harm peaked in 2007 (IR 25.1) and then decreased consistently year on year to 13.8 in 2016. This pattern was found in all age groups, in both males and females and in each parental income tertile. During the last 6 years of the observation period, 2011-2016, girls aged 13-16 had the highest incidence rates whereas, among boys, incidence was highest among 17-19 year olds throughout. CONCLUSIONS: The temporal increases in incidence rates of self-harm among adolescents observed in some Western European countries experiencing major economic recession were not observed in Denmark. Restrictions to sales of analgesics, access to dedicated suicide prevention clinics, higher levels of social spending and a stronger welfare system may have protected potentially vulnerable adolescents from the increases seen in other countries. A better understanding of the specific mechanisms behind the temporal patterns in self-harm incidence in Denmark is needed to help inform suicide prevention in other nations.

Outcomes after craniotomy for resection of craniopharyngiomas in adults: analysis of the National Surgical Quality Improvement Program (NSQIP).

PURPOSE: Craniopharyngiomas occur in suprasellar locations that pose challenges for surgical management. This study evaluates the incidence of complications following craniotomy for craniopharyngioma in adults and investigates risk factors for these complications. METHODS: Patients who underwent craniotomy for excision of craniopharyngioma were identified from the 2005-2016 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Incidence of 30-day postoperative complications was determined. Multivariable logistic regression identified demographic, comorbid and perioperative characteristics associated with any complication and major (Clavien IV) complications.  RESULTS: There were 143 cases identified. Fifty-one (35.7%) had a complication, twenty (14.0%) experienced a major complication and there were four (2.8%) deaths. The most common complications were: unplanned readmission (13.3%), prolonged ventilation > 48 h (9.8%), and unplanned reoperation (9.3%). In multivariable analysis, variables significantly associated with any complication were: black race (OR 0.16; 95% CI 0.03-0.84; p = 0.03), hypertension (OR 5.04; 95% CI 1.79-14.17; p = 0.002) and longer duration of surgery (OR 1.27; 95% CI 1.01-1.58; p = 0.04). Hypertension (OR 9.33; 95% CI 1.61-54.21; p = 0.01) and longer duration of surgery (OR 1.51; 95% CI 1.05-2.17; p = 0.03) were also significant predictors for major complications. CONCLUSION: One-third of patients undergoing craniotomy for craniopharyngioma resection experienced a postoperative complication. While high, this contrasts previously reported rates of two-thirds. Prolonged operative time and hypertension are positive predictors of major complications. This information can assist in counseling patients and decision-making for management. We note that other treatment approaches, such as endoscopic surgical techniques, radiosurgery and radiation therapy likely have different profiles and predictors of complications.

Comparison of ABC/2 estimation and a volumetric computerized method for measurement of meningiomas using magnetic resonance imaging.

INTRODUCTION: Measurement of tumor growth rates over time for patients with meningiomas has important prognostic and therapeutic implications. Our objective was to compare two methods of measuring meningioma volume: (1) the simplified ellipsoid (ABC/2) method; and (2) perimetric volume measurements using imaging software modules. METHODS: Patients with conservatively managed meningiomas for at least 1.5 years were retrospectively identified from the VCU Brain and Spine Tumor Registry over a 10-year period (2005-2015). Tumor volumes were independently measured using the simplified ellipsoid and computerized perimetric methods. Intra class correlations (CC) and Bland-Altman analyses were performed. RESULTS: A total of 26 patients representing 29 tumors were identified. Across 146 images, there were 24 (16%) images that were non-measurable using standard application commands with the computerized perimetric method. The mean volume obtained using the ABC/2 and computerized perimetric methods were 3.2 ± 3.4 cm3 and 3.4 ± 3.5 cm3, respectively. The mean volume difference was 0.2 cm3 (SE = 0.12; p = 0.10) across measurement methods. The concordance correlation coefficient (CCC) between methods was 0.95 (95% CI 0.91, 0.98). CONCLUSIONS: There is excellent correlation between the simplified ellipsoid and computerized perimetric methods of volumetric analysis for conservatively managed meningiomas. The simplified ellipsoid method remains an excellent method for meningioma volume assessment and had an advantage over the perimetric method which failed to allow measurement of roughly one in six tumors on imaging.

Enhanced plasmid-mediated bioaugmentation of RDX-contaminated matrices in column studies using donor strain Gordonia sp. KTR9.

Horizontal gene transfer (HGT) is the lateral movement of genetic material between organisms. The RDX explosive-degrading bacterium Gordonia sp. KTR9 has been shown previously to transfer the pGKT2 plasmid containing the RDX degradative genes (xplAB) by HGT. Overall, fitness costs to the transconjugants to maintain pGKT2 was determined through growth and survivability assessments. Rhodococcus jostii RHA1 transconjugants demonstrated a fitness cost while other strains showed minimal cost. Biogeochemical parameters that stimulate HGT of pGKT2 were evaluated in soil slurry mating experiments and the absence of nitrogen was found to increase HGT events three orders of magnitude. Experiments evaluating RDX degradation in flow-through soil columns containing mating pairs showed 20% greater degradation than columns with only the donor KTR9 strain. Understanding the factors governing HGT will benefit bioaugmentation efforts where beneficial bacteria with transferrable traits could be used to more efficiently degrade contaminants through gene transfer to native populations.

Effects of chitin and temperature on sub-Arctic soil microbial and fungal communities and biodegradation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and 2,4-dinitrotoluene (DNT).

Climate warming in the Arctic and the thawing of frozen carbon stocks are leading to uncertainty as to how bacterial communities will respond, including pollutant degrading bacteria. This study investigated the effects of carbon stimulation and temperature on soil microbial community diversity and explosive biodegradation in two sub-Arctic soils. Chitin as a labile carbon source stimulated overall microbial activities as reflected by increases in basal respiration (three to tenfold) and potential nitrification activity (two to fourfold) compared to unamended soil. This stimulation extended to 2,4-dinitroluene- (DNT) and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX)-degrading microorganisms either directly or via co-metabolic reaction mechanisms. A stimulatory effect of the incubation temperature (2, 12, or 22 °C) on these microbial activities was also observed, but the chitin stimulation caused greater shifts in the structure of the bacterial and fungal communities. The first reported occurrence of an associated role of chitinolytic bacteria belonging to Cellulomonadaceae and chitinolytic fungi belonging to Mortierellaceae in explosive biodegradation is described. This study found that sub-Arctic soil microbial communities were adapted to respond quickly to an increase in labile carbon sources over the range of temperatures used in this study. The warming climate in the Arctic could benefit explosive contaminated soil clean-up by providing non-recalcitrant carbon sources that stimulate overall microbial activity and correspondingly explosive biodegradation.

Keratinocyte-Releasable Factors Stimulate the Expression of Granulocyte Colony-Stimulating Factor in Human Dermal Fibroblasts.

Interaction between keratinocytes and fibroblasts plays a critical role in maintaining skin integrity under both normal and pathological conditions. We have previously demonstrated that keratinocyte-releasable factors influence the expression of key extracellular matrix components, such as collagen and matrix metalloproteinases in dermal fibroblasts. In this study, we utilized DNA microarray analysis to examine the effects of keratinocyte-releasable factors on the expression of several cytokines in human dermal fibroblasts. The results revealed significantly higher granulocyte colony-stimulating factor (G-CSF) expression in fibroblasts co-cultured with keratinocytes relative to mono-cultured cells, which was verified by RT-PCR and western blot. G-CSF is an important hematopoietic factor also thought to play a beneficial role in wound healing through stimulating keratinocyte proliferation. To partially characterize the keratinocyte-releasable factors responsible for stimulating G-CSF production, keratinocyte-conditioned medium (KCM) was subjected to thermal treatment and ammonium sulfate precipitation before treating fibroblasts. The results showed that keratinocyte-releasable G-CSF-stimulating factors remain stable at 56°C and upon 50% ammonium sulfate precipitation. Knowing that keratinocytes release IL-1, which stimulates G-CSF expression in various immune cells, several experiments were conducted to ask whether this might also be the case for fibroblasts. The results showed that the addition of recombinant IL-1 markedly increased G-CSF expression in fibroblasts; however, IL-1 receptor antagonist only partially abrogated KCM-stimulated G-CSF expression, indicating the role of additional keratinocyte-releasable factors. These findings underline the importance of cross-talk between keratinocytes and fibroblasts, suggesting that communication between these cells in vivo modulates the production of cytokines required for cutaneous wound healing and maintenance. J. Cell. Biochem. 118: 308-317, 2017. © 2016 Wiley Periodicals, Inc.