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Despite the advancements in the development of pharmacological interventions for personality disorders (PDs), clinicians should be relatively cautious about the potential benefits of using pharmacological agents for the treatment of PDs when facing therapeutic decisions for individual patients. The pharmacological management of PDs is considerably complex; frequent treatment drop-out, non-compliance, and adverse effects illustrate why having a good therapeutic relationship with patients is a particularly important factor for the success of pharmacological treatment of PDs. Results from clinical trials for PDs may not be generalizable for individual patients in the community. PDs are heterogeneous conditions associated with many psychiatric disorders. Yet, clinical trials frequently include highly selected populations that do not necessarily correspond to typical patients with PDs found in community settings. Considering that PDs frequently co-occur with other psychiatric diagnoses, a promising approach to future research in PDs should consider the development of treatment algorithms based on co-occurring disorders. This approach is likely to resonate with prescribing physicians trained to evaluate patients systematically for the presence or absence of specific disorders. For instance, this approach has been increasingly studied in gambling disorder, with promising findings reported thus far.
Pharmacological management of personality disorders (PD) is controversial and some guidelines state medications are not to be used. Yet prescribing medications is endemic in practice. This chapter reviews recent evidence regarding the use of medication for PD patients; and novel approaches highlighting possible neuropathological mechanisms and a clinical approach to psychopharmacological management.
Current approaches for early identification of individuals at high risk for autism spectrum disorder (ASD) in the general population are limited, and most ASD patients are not identified until after the age of 4. This is despite substantial evidence suggesting that early diagnosis and intervention improves developmental course and outcome. The aim of the current study was to test the ability of machine learning (ML) models applied to electronic medical records (EMRs) to predict ASD early in life, in a general population sample.
We used EMR data from a single Israeli Health Maintenance Organization, including EMR information for parents of 1,397 ASD children (ICD-9/10) and 94,741 non-ASD children born between January 1st, 1997 and December 31st, 2008. Routinely available parental sociodemographic information, parental medical histories, and prescribed medications data were used to generate features to train various ML algorithms, including multivariate logistic regression, artificial neural networks, and random forest. Prediction performance was evaluated with 10-fold cross-validation by computing the area under the receiver operating characteristic curve (AUC; C-statistic), sensitivity, specificity, accuracy, false positive rate, and precision (positive predictive value [PPV]).
All ML models tested had similar performance. The average performance across all models had C-statistic of 0.709, sensitivity of 29.93%, specificity of 98.18%, accuracy of 95.62%, false positive rate of 1.81%, and PPV of 43.35% for predicting ASD in this dataset.
We conclude that ML algorithms combined with EMR capture early life ASD risk as well as reveal previously unknown features to be associated with ASD-risk. Such approaches may be able to enhance the ability for accurate and efficient early detection of ASD in large populations of children.
Our brains are continuously changing and these changes alter brain functions. With maturation, there is growth and unfortunately, even with healthy aging, decline. Aging-related decrements affect neurons and their connectivity, neurotransmitter systems, and even support systems such as glia. Aging affects some brain regions (frontal lobes and hippocampi) more than others. This book reviews and discusses aging-related changes and their influence on the major neurobehavioral domains, beginning with reviews of aging-related changes in anatomy and physiology. Subsequent chapters review cross-sectional and longitudinal studies of aging-related changes in sensory perception (vision, hearing, touch, smell, taste) and cognitive functions (memory, language, motor planning, attention, executive functions, emotions, creativity). In each chapter, mechanisms that may account for these changes are discussed. Declines related to aging per se are distinguished from declines related to aging-associated diseases. Final chapters discuss what can potentially be done to slow or reverse aging-related decline of cognitive functions, including exercise, cognitive rehabilitation, and pharmacological agents. It is hoped this book will help clinicians differentiate between normal aging processes and brain diseases, reduce the adverse effects of brain aging, and stimulate further research on how adverse effects of brain aging can be reversed, stopped, modified, or best managed.
“Cosmetic neurology,” also referred to as “cognitive enhancement,” is the practice of enhancing cognition and behavior in healthy people. Although cosmetic neurology often refers to the enhancement of cognition, it can also refer to the enhancement of mood, movement, creativity, social finesse, and other psychological attributes. Cosmetic neurology carries the promise of an improved quality of life and productivity well into old age, as well as potential medical and social perils. In this chapter, we review our understanding of the efficacy of drugs including stimulants and cholinesterase inhibitors that can be used for enhancement. We review their potential benefits to the individual and society. We also place the practice of cosmetic neurology in the context of current cultural norms and outline ethical concerns that this practice generates.
Although alcohol withdrawal is common, the recognition of benzodiazepine-resistant alcohol withdrawal is a relatively new concept. To provide a framework for both literature review and future research, we assessed clinicians’ personal definition of resistant alcohol withdrawal.
We developed a cross-sectional web-based survey. Administrators from collaborating toxicology and emergency medicine associations deployed the survey directly to their respective memberships. Only physicians, pharmacists, and other clinicians routinely treating alcohol withdrawal were eligible to participate. Respondents selected their preferred definition among the three most common author sources – JB Hack, NJ Benedict, D Hughes – or provided their own. Additional criteria to define resistant alcohol withdrawal were explored.
384 individuals answered the survey. Respondents were mostly attending physicians (79%), in full-time practice (90%), in emergency medicine (70%), and from North America (90%). The majority (64%) described resistant alcohol withdrawal as a high benzodiazepine dosage. Seizures (26%) and persistent tachycardia (16%) were also main characteristics. The median dose to describe high benzodiazepine dose (n = 146) was 40 mg per hour of diazepam equivalents (IQR 20–50). Available definitions were ranked equally as the preferred one: Hack (27%); Benedict (28%); Hughes (28%).
Our results did not identify one single preferred definition for resistant alcohol withdrawal even though a high total dose of benzodiazepine is a major component. Hourly requirements of 40 mg of diazepam equivalents or more emerged as a possible threshold. These findings serve as a base to explore consensus guidelines or future research.
Fe deficiency (ID) defined as plasma ferritin <12 µg/l is associated with delayed cognitive development in early childhood and increased incidence of infections; however, the longitudinal association between early-life factors and ID in 18-month-old children in Denmark is unknown. The present study aimed to determine the prevalence of ID and to describe risk factors associated with ID in healthy 18-month-old Danish children. Blood samples, anthropometric measurements and self-reported questionnaire data had been obtained in the birth cohort, Odense Child Cohort. The questionnaires were modified from those used in the Danish National Birth Cohort. Plasma ferritin and C-reactive protein in venous, non-fasting samples were analysed in the final sample size of 370 children after exclusion of seventy-nine children due to chronic disease, acute infection, C-reactive protein >10 mg/l, twin birth or prematurity. Associations with ID were analysed by logistic regression, adjusting for sex, maternal education, duration of partial breast-feeding and current intake of milk, fish and meat. Overall, fifty-six children had ID (15·1 %). Factors associated with increased risk were exclusive breast-feeding beyond 4 months (OR 5·97; 95 % CI 1·63, 21·86) and no intake of oral Fe supplements from 6 to 12 months (OR 3·99, 95 % CI 1·33, 11·97. Duration of partial breast-feeding and current diet was not associated with ID. In conclusion, the ID prevalence was 15·1 %, and both exclusive breast-feeding beyond 4 months and no intake of oral Fe supplements from 6 to 12 months were associated with increased risk of ID in 18-month-old children.
Sarcosine, which is freely sold as a dietary supplement, has pharmacological activity to boost functioning of the glutamatergic N-methyl-d-aspartate receptor (NMDAR) and hence it is a biologically rational treatment for schizophrenia. The small number of studies carried out to date provide some evidence for its efficacy and psychiatrists could consider suggesting its use to their patients.
In major depression, remission rate in response to monoaminergic antidepressant is around 50%. The lack of strong synergies between classical antidepressants and psychotherapy may be due to the molecular effects of classical antidepressants. They modulate synapses but they do not substantially influence synaptogenesis. They also increase brain-derived neurotrophic factor (BDNF). However, for activity-dependent plasticity, BDNF release has to work in concert with activation of synaptogenesis. There has been considerable excitement about ketamine’s antidepressant effect. Ketamine leads to fast changes in synaptic function and plasticity that go well beyond effects of classical antidepressants. As a result, ketamine may turn out to have the capacity to considerably enhance the effects of psychotherapy. Such enhancing effects may become an important clinical indication for ketamine since its purely pharmacological effect is transient. This editorial outlines some mechanistic hypotheses, how Behavioral Activation, Trauma-Focused Psychotherapies and Humanistic Psychotherapy may specifically prolong ketamine’s antidepressant effects.
The ventricular assist device is being increasingly used as a “bridge-to-transplant” option in children with heart failure who have failed medical management. Care for this medically complex population must be optimised, including through concomitant pharmacotherapy. Pharmacokinetic/pharmacodynamic alterations affecting pharmacotherapy are increasingly discovered in children supported with extracorporeal membrane oxygenation, another form of mechanical circulatory support. Similarities between extracorporeal membrane oxygenation and ventricular assist devices support the hypothesis that similar alterations may exist in ventricular assist device-supported patients. We conducted a literature review to assess the current data available on pharmacokinetics/pharmacodynamics in children with ventricular assist devices. We found two adult and no paediatric pharmacokinetic/pharmacodynamic studies in ventricular assist device-supported patients. While mechanisms may be partially extrapolated from children supported with extracorporeal membrane oxygenation, dedicated investigation of the paediatric ventricular assist device population is crucial given the inherent differences between the two forms of mechanical circulatory support, and pathophysiology that is unique to these patients. Commonly used drugs such as anticoagulants and antibiotics have narrow therapeutic windows with devastating consequences if under-dosed or over-dosed. Clinical studies are urgently needed to improve outcomes and maximise the potential of ventricular assist devices in this vulnerable population.
Introduction: NSAIDS offer more effective analgesia than opioids, require less rescue medication, and decrease the incidence of nausea and vomiting in renal colic patients. Alpha blockers and Opioids are also prescribed frequently, but doses used and treatment durations are not well described. Our objective was to investigate ED prescribing decisions and medication compliance by patients with acute renal colic. Methods: In this prospective two-city cohort study, we invited patients with a first ED visit for image-confirmed 2-10 mm ureteric stones to consent to a telephone survey 10 days after their ED visit. During follow-up interviews, patients were asked what drugs they were prescribed and how many doses they required. This study was REB approved. Results: A convenience sample of 224 patients, including 152 males (67.9%) and 72 females (median age= 52.4 years) completed 10-day surveys. NSAIDS were prescribed for 48.7%, tamsulosin for 65.2% and opioids for 81.7%. One-third received a tamsulosin-NSAID combination, 40% an opioid-NSAID combination and 28% a tamsulosin-NSAID-opioid combination. Of 109 patients prescribed an NSAID, only 70 (64.2%) took 1 dose/day; however an additional 28 who were not prescribed NSAIDs took 1 NSAID dose/day. Mean (sd) NSAID intake in the overall study group was 1.1 (1.5) doses/day from day 1-5 and 0.6 (1.1) doses/day on days 6-10, with 90%ile values of 3.0 and 2.0 doses/day. NSAID compliance was more common in patients who stated they received high quality discharge instructions (63.8% vs. 32.6%; RR=1.95; 95% CI 1.47-2.60). Mean opioid intake in the overall study group was 1.2 (1.7) doses/day from day 1-5 and 0.5 (1.3) doses/day on days 6-10, with 90%ile values of 4.0 and 2.0 doses/day. Among patients prescribed tamsulosin, the average was 4.0 days of compliance (sd=4.3), with a 90%ile value of 10 days. Conclusion: This study provides estimates for the amount of drug actually used by renal colic patients during the 10-days after their ED visit. Patients used fewer opioid doses than expected, and NSAID and tamsulosin compliance appears relatively poor. NSAID compliance was better in patients who perceived high quality discharge instructions. This study suggests there is room for improvement in medication prescribing and discharge instructions for ED patients with an acute episode of ureteral colic.
Introduction: Emergency department (ED) physicians strive to provide analgesia, amnesia and sedation for patients when performing painful procedures through the use of procedural sedation (PS). Examination of the literature suggests that the application of PS appears to be variable with institutional influences and clinician disagreement on pharmacology, airway management, and monitoring. The primary goal of this research project was to describe the variability of practice with respect to pharmacologic choices and clinical applications of PS among Canadian ED physicians. Methods: An electronic survey was distributed through the Canadian Association of Emergency Physicians (CAEP). Practicing physician members of CAEP were invited to complete the survey. The 20 question survey encompassed various aspects of PS including physician choices regarding PS indications and pharmacology. The primary outcome was the quantification of practice variability among ED physicians with respect to the above listed aspects of PS. The data was presented with simple descriptive statistics. Results: To date, 278 ED physicians responded to our survey (response rate 20.3%). Respondents were primarily academic hospital (53.2%) or community hospital based (38.2%). With emergency medicine training as: CCFP-EM (55.2%), FRCPC (30.1%), and CCFP (9.0%). There was relative agreement on the following interventions requiring PS: 98.4% applied PS for electrical cardioversion and 98.1% for brief (<10 mins) orthopedic manipulations. However, only 36.3% utilized PS for burn debridement in the ED. PS was utilized less frequently (78.1%) for prolonged (>10mins) orthopedic manipulations than brief manipulations. For all procedures aggregated, in hemodynamically stable patients with an American Society of Anesthesiology (ASA) score of 1, ED physicians utilized propofol 76.3% of the time. Additional agents were utilized at the following rates: fentanyl-propofol (7.6%), ketamine (7.6%), and fentanyl (4%). This inclination towards propofol alone appears to be consistent across modality of ER training, type of ER setting (rural vs academic), and volume of PS performed. Conclusion: This study demonstrates that Canadian ED physicians have a clear preference for propofol as a first line pharmacologic agent when administering PS in hemodynamically stable, ASA1 patients. Conversely, there appears to be more variation amongst ED physicians with respect to second line pharmaceutical choices for PS.
Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.
Discovered by farmers from an unmarked tomb in 1972 in Gansu, the Wuwei strips and tablets set forth a wealth of information about ancient Chinese drug formulary and acupuncture. The present article supplies the first English-language translation of its contents along with a brief introduction.
Our knowledge and understanding of the underlying neurobiology and symptomatic expression of ADHD has advanced dramatically over the past decade. Associated with these advances has been a similar explosion of new treatment options to individualize treatment for our patients.
This article will:
∙review strategies to measure ADHD symptoms and functional difficulties while seeking to achieve full symptomatic remission throughout the day
∙summarize recent findings regarding the management and prioritization of ADHD and comorbid conditions and
∙discuss the various pharmacologic treatment options with a focus on recently developed molecules and novel delivery systems