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This study aimed to report the pre- and post-operative laryngeal endoscopic findings in patients referred by non-otolaryngologists who are undergoing thyroid and/or parathyroid surgery, and to determine the number and nature of referrals before and after the release of the clinical practice guideline for improving voice outcomes after thyroid surgery.
This retrospective cohort study, conducted at a tertiary care academic hospital, comprised adult patients referred by the endocrine surgery service for laryngoscopy from 2007 to 2018 (n = 166). Data regarding patient demographics, reason for referral and endoscopic findings were recorded.
The number of referrals increased significantly after the release of the practice guideline. The most common indication for referral pre- and post-operatively was voice change. The most common finding during laryngoscopy was normal examination findings (pre-operatively) and unilateral vocal fold immobility (post-operatively).
Peri-operative thyroid and/or parathyroid patients have laryngoscopic findings other than vocal fold immobility. Laryngoscopy to detect structural and functional pathology is warranted.
The ‘16Up’ study conducted at the QIMR Berghofer Medical Research Institute from January 2014 to December 2018 aimed to examine the physical and mental health of young Australian twins aged 16−18 years (N = 876; 371 twin pairs and 18 triplet sets). Measurements included online questionnaires covering physical and mental health as well as information and communication technology (ICT) use, actigraphy, sleep diaries and hair samples to determine cortisol concentrations. Study participants generally rated themselves as being in good physical (79%) and mental (73%) health and reported lower rates of psychological distress and exposure to alcohol, tobacco products or other substances than previously reported for this age group in the Australian population. Daily or near-daily online activity was almost universal among study participants, with no differences noted between males and females in terms of frequency or duration of internet access. Patterns of ICT use in this sample indicated that the respondents were more likely to use online information sources for researching physical health issues than for mental health or substance use issues, and that they generally reported partial levels of satisfaction with the mental health information they found online. This suggests that internet-based mental health resources can be readily accessed by adolescent Australians, and their computer literacy augurs well for future access to online health resources. In combination with other data collected as part of the ongoing Brisbane Longitudinal Twin Study, the 16Up project provides a valuable resource for the longitudinal investigation of genetic and environmental contributions to phenotypic variation in a variety of human traits.
Loneliness is related to mental and somatic health outcomes, including borderline personality disorder. Here, we analyze the sources of variation that are responsible for the relationship between borderline personality features (including four dimensions, affective instability, identity disturbance, negative relationships, self-harm and a total score) and loneliness. Using genetically informative data from two large nonclinical samples of adult twin pairs from Australia and the Netherlands (N = 11,329), we estimate the phenotypic, genetic and environmental correlations between self-reported borderline personality features and loneliness. Individual differences in borderline personality and loneliness were best explained by additive genetic factors with heritability estimates h2 = 41% for the borderline personality total score and h2 = 36% for loneliness, with the remaining variation explained by environmental influences that were not shared by twins from the same pair. Genetic and environmental factors influencing borderline personality (total score and four subscales separately) were also partial causes of loneliness. The correlation between loneliness and the borderline personality total score was rph = .51. The genetic correlation was estimated at rg = .64 and the environmental correlation at re = .40. Our study suggests common etiological factors in loneliness and borderline personality features.
Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series.
This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences.
We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions.
The cases of individuals with DLB took longer to reach a final diagnosis (1.2 v. 0.6 years, P = 0.017), underwent more scans (1.7 v. 1.2, P = 0.002) and had more alternative prior diagnoses (0.8 v. 0.4, P = 0.002), than the cases of those with non-DLB dementia. Individuals diagnosed in one region of the UK had significantly more core features (2.1 v. 1.5, P = 0.007) than those in the other region, and were less likely to have dopamine transporter imaging (P < 0.001). For patients with PDD, more than 1.4 years prior to receiving a dementia diagnosis: 46% (12 of 26) had documented impaired activities of daily living because of cognitive impairment, 57% (16 of 28) had cognitive impairment in multiple domains, with 38% (6 of 16) having both, and 39% (9 of 23) already receiving anti-dementia drugs.
Our results show the pathway to diagnosis of DLB is longer and more complex than for non-DLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. For PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.
Our group has pioneered research indicating that Developmental vitamin D (DVD) deficiency (a candidate risk factor for schizophrenia) alters both brain development and function. We have convergent evidence indicating a disturbance in dopamine signalling in this model. 1stly the superior colliculus (the proto-basal ganglia) is the initial site where the vitamin D receptor is expressed in foetal brain; 2ndly we show a reduction in Catechol-O-methyl transferase (a major metabolic enzyme for dopamine) in these foetal brains; 3rdly dopamine metabolites in the DVD deplete neonatal brain reflect this enzymatic change. When we allow these animals to mature under vitamin D normal conditions we repeatedly observe alterations in both spontaneous and psychomimetic enhanced locomotion. Consistent with the theme of persistent changes in dopamine signalling in this model we now present new data showing that dopamine transporter density and/or affinity are altered in DVD deplete female offspring whilst DA 1 receptor density and dopamine cell number are reduced in DVD deplete male offspring (all P< 0.05 n>8).
Our most recent studies indicate that Nurr-1, a nuclear transcription regulator important in both bone and dopamine neuron development and survival may be a molecular mediator of these processes. Nurr-1 is upregulated by parathyroid hormone (PTH). PTH levels are 2-3 fold greater in vitamin D deficient Dams across gestation. Most importantly we have just shown that Nurr-1 is dose-dependently upregulated by parathyroid hormone (PTH) in a neuroblastoma cell line.
Our findings strongly suggest that vitamin D directly (or indirectly via PTH) mediates dopamine neuron development.
We investigate generalized Navier–Stokes (GNS) equations that couple nonlinear advection with a generic linear instability. This analytically tractable minimal model for fluid flows driven by internal active stresses has recently been shown to permit exact solutions on a stationary two-dimensional sphere. Here, we extend the analysis to linearly driven flows on rotating spheres. We derive exact solutions of the GNS equations corresponding to time-independent zonal jets and superposed westward-propagating Rossby waves, qualitatively similar to those seen in planetary atmospheres. Direct numerical simulations with large rotation rates obtain statistically stationary states close to these exact solutions. The measured phase speeds of waves in the GNS simulations agree with analytical predictions for Rossby waves.
It is easy to find texts, in scientific literature, studying the adaptation of immigrants from developing countries in western countries. However, in these globalization times that we are living, few are the studies performed on members from developed countries emigrating to the third world.
To evaluate the factors predisposing to the onset of anxiety or depression symptoms in Spanish immigrants living in South Africa.
This is an exploratory study with a sample of 51 Spanish residents in South Africa between 24 and 57 years (44% male, 56% female), 44% of which were living there for more than two years. An online survey was administered, collecting data related to reasons and conditions for their moving to the country and traumatic events living during the stay. For the screening of depression and anxiety symptoms Hopkins Symptom Scale (HSCL-25) was used. Finally, we carried about several analysis using Chi2 test. For statistical analysis SPSS was utilized.
Thirty percent of the sample showed positive scores on anxiety symptoms scale, and 24% scored positive for depression. Job related items as being unemployed (P < 0.001) was associated to symptoms of depression. Insecurity/violence (P < 0.021) and race discrimination (P < 0.009) were the main factors related to anxiety symptoms.
Factor related to employment, security and discrimination, has been significantly associated to the onset of anxiety and depression symptoms. Other factors related to the moving to the country or social relationships have shown no relations. More studies are needed to provide information about adaptation and factors related to mental health in Occidental immigrants in developing countries.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Patients diagnosed with glioblastoma (GBM) are treated with surgery followed by fractionated radiotherapy with concurrent and adjuvant temozolomide. Patients are monitored with serial magnetic resonance imaging (MRI). However, treatment-related changes frequently mimic disease progression. We reviewed a series of patients undergoing surgery for presumed first-recurrence GBM, where pathology reports were available for tissue diagnosis, in order to better understand factors associated with a diagnosis of treatment-related changes on final pathology.
Patient records at a single institution between 2005 and 2015 were retrospectively reviewed. Pathology reports were reviewed to determine diagnosis of recurrent GBM or treatment effect. Survival analysis was performed interrogating overall survival (OS) and progression-free survival (PFS). Correlation with radiation treatment plans was also examined.
One-hundred-twenty-three patients were identified. One-hundred-sixteen patients (94%) underwent resection and seven underwent biopsy. Treatment-related changes were reported in 20 cases (16%). These patients had longer median OS and PFS from the time of recurrence than patients with true disease progression. However, there was no significant difference in OS from the time of initial diagnosis. Treatment effect was associated with surgery within 90 days of completing radiation. In patients receiving radiation at our institution (n = 53), larger radiation target volume and a higher maximum dose were associated with treatment effect.
Treatment effect was associated with surgery nearer to completion of radiation, a larger radiation target volume, and a higher maximum point dose. Treatment effect was associated with longer PFS and OS from the time of recurrence, but not from the time of initial diagnosis.
Historically, Parkinson's disease was viewed as a motor disorder and it is only in recent years that the spectrum of non-motor disorders associated with the condition has been fully recognised. There is a broad scope of neuropsychiatric manifestations, including depression, anxiety, apathy, psychosis and cognitive impairment. Patients are more predisposed to delirium, and Parkinson's disease treatments give rise to specific syndromes, including impulse control disorders, dopamine agonist withdrawal syndrome and dopamine dysregulation syndrome. This article gives a broad overview of the spectrum of these conditions, describes the association with severity of Parkinson's disease and the degree to which dopaminergic degeneration and/or treatment influence symptoms. We highlight useful assessment scales that inform diagnosis and current treatment strategies to ameliorate these troublesome symptoms, which frequently negatively affect quality of life.
Thank you so much, Catherine, and to Sean and to Mark and all of you who have put this together. The annual ASIL event is something all of us lawyers look forward to every year, where we have an opportunity to hear some of the remarkable things that people are doing and thinking about and moving the conversation forward, and I agree it is a critical moment.
The goals of the present study were to examine the associations between depressive symptoms, sleep problems and the risk of developing heart disease in a Canadian community sample.
Baseline data were from the CARTaGENE study, a community health survey of adults aged 40–69 years in Quebec, Canada. Incidence of heart disease was examined in N = 33 455 participants by linking survey data with administrative health insurance data. Incident heart disease was identified using the World Health Organization's International Classification of Diseases, 9th or 10th edition (ICD-9 and ICD-10) diagnostic codes for heart disease. Sleep problems were assessed with diagnostic codes for sleep disorders within the 2 years preceding the baseline assessment. Average sleep duration was assessed by self-report. Depressive symptoms were assessed with the nine-item Patient Health Questionnaire.
In total, 2448 (7.3%) participants developed heart disease over an average follow-up period of 4.6 years. Compared to those without depressive symptoms and with no sleep disorders, those with elevated depressive symptoms and a sleep disorder (HR = 2.60, 95% CI 1.83–3.69), those with depressive symptoms alone (HR = 1.40, 95% CI 1.25–1.57) and those with sleep disorders alone (HR = 1.33, 95% CI 1.03–1.73) were more likely to develop heart disease. Test of additive interaction suggested a synergistic interaction between depressive symptoms and sleep disorders (synergy index = 2.17 [95% CI 1.01–4.64]). When sleep duration was considered, those with long sleep duration and elevated depressive symptoms were more likely to develop heart disease than those with long sleep alone (HR = 1.77, 95% CI 1.37–2.28; and HR = 1.16, 95% CI 0.99–1.36, respectively).
Depression and diagnosed sleep disorders or long sleep duration are independent risk factors for heart disease and are associated with a stronger risk of heart disease when occurring together.
Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.
1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.
At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.
Funding Acknowledgements: This study was supported by Assurex Health, Inc.
I. De Pater, University of California, Berkeley Berkeley, California, USA,
D. P. Hamilton, University of Maryland College Park, Maryland, USA,
M. R. Showalter, SETI Institute Mountain View, California, USA,
H. B. Throop, Planetary Science Institute Tucson, Arizona, USA,
J. A. Burns, Cornell University Ithaca, New York, USA
Previous studies have examined associations of cardiometabolic factors with depression and cognition separately.
To determine if depressive symptoms mediate the association between cardiometabolic factors and cognitive decline in two community studies.
Data for the analyses were drawn from the Rotterdam Study, the Netherlands (n = 2940) and the Whitehall II study, UK (n = 4469).
Mediation analyses suggested a direct association between cardiometabolic factors and cognitive decline and an indirect association through depression: poorer cardiometabolic status at time 1 was associated with a higher level of depressive symptoms at time 2 (standardised regression coefficient 0.07 and 0.06, respectively), which, in turn, was associated with greater cognitive decline between time 2 and time 3 (standardised regression coefficient of −0.15 and −0.41, respectively).
Evidence from two independent cohort studies suggest an association between cardiometabolic dysregulation and cognitive decline and that depressive symptoms tend to precede this decline.
There is growing interest in linking vitamin D deficiency with autism spectrum disorders (ASDs). The association between vitamin D deficiency during gestation, a critical period in neurodevelopment, and ASD is not well understood.
To determine the association between gestational vitamin D status and ASD.
Based on a birth cohort (n=4334), we examined the association between 25-hydroxyvitamin D (25OHD), assessed from both maternal mid-gestation sera and neonatal sera, and ASD (defined by clinical records; n=68 cases).
Individuals in the 25OHD-deficient group at mid-gestation had more than twofold increased risk of ASD (odds ratio (OR)=2.42, 95% confidence interval (CI) 1.09 to 5.07, P=0.03) compared with the sufficient group. The findings persisted in analyses including children of European ethnicity only.
Mid-gestational vitamin D deficiency was associated with an increased risk of ASD. Because gestational vitamin D deficiency is readily preventable with safe, inexpensive and readily available supplementation, this risk factor warrants closer scrutiny.