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440 Muscle Protein Synthesis and Whole-Body Protein Balance Following Ingestion of Beef or a Soy Protein Based Meat Alternative
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- David D. Church, Katie R. Hirsch, Shiloah A. Kviatkovsky, Arny A. Ferrando, Gohar Azhar, Robert R Wolfe
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- Journal:
- Journal of Clinical and Translational Science / Volume 8 / Issue s1 / April 2024
- Published online by Cambridge University Press:
- 03 April 2024, pp. 130-131
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OBJECTIVES/GOALS: We endeavor to investigated the hypothesis that muscle protein synthesis (MPS) is stimulated more after consumption of a 4-ounce beef patty as compared to 4- and 8-ounces of a soy protein based meat alternative (SPBMA) and if a greater stimulation is related to differences in the responses of plasma essential amino acid (EAA) concentrations. METHODS/STUDY POPULATION: Participants were aged 18 to 40 years of age with a BMI between 20 and 32 kg/m2. Written informed consent was obtained from all participants, and approved by UAMS IRB. Participants were assigned to one of three intervention groups via a single-blinded permuted block randomization, stratified for sex: 4 oz beef patty; 4 oz SPBMA; 2 x 4 oz (8oz) SPBMA. The impossible burgerTM was selected as it is primarily soy protein, a high-quality plant protein, and specifically designed to mimic a beef burger. Stable isotope were infused to assess protein metabolism. Appropriate muscle and blood samples were obtained. Enrichment and plasma EAA concentrations were measured with mass spectrometry. ANOVA’s on the change from basal to postprandial were used to identify group difference, significance was accepted at p < 0.05. RESULTS/ANTICIPATED RESULTS: The MPS increase from basal to postprandial indicated a significant main effect of group (p = 0.026), with the beef group (0.020 ± 0.016%/hour) being significantly greater than the 4oz SPBMA (0.003 ± 0.010%/hour; p = 0.021) but not the 8oz PBMA group (0.013 ± 0.016%/hour; p = 0.454). Similar results were observed for whole-body protein synthesis, where the beef group (p = 0.042) and 8oz SPBMA (p = 0.033) were significantly greater than the 4oz SPBMA (p = 0.021). Whole-body protein balance was significantly greater in the 8oz SPBMA as compared to 4oz of beef and SPBMA. Lastly, we observed a significantly relationship (p = 0.046; r = 0.411) between the maximal plasma EAA concentration and change in MPS, indicating the greater rate of MPS following 4oz of beef is mediated by an higher increase in plasma EAA concentrations. DISCUSSION/SIGNIFICANCE: In conclusion, 4oz of beef stimulates muscle protein FSR more than 4oz of a SPBMA. A common SPBMA can stimulate increase in protein metabolism, however, greater amounts are required as compared to beef protein. Further, the change in the muscle protein FSR response was significantly correlated with the maximal EAA concentration.
To Sleep Perchance to Dream - Not; Nyctophobia From COVID-19 Induced Hyposmia
- S. Kalita, D. Birwatkar, R. Cosme, A. Hirsch
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S807
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Introduction
Fear of sleep (nyctophobia), has been attributed to myriad conditions ranging from benign nocturnal panic attacks and Morvan’s syndrome (Ekambaram, 2021). Positional dependent hyposmia as an origin of nyctophobia has not heretofore been described.
ObjectivesIncrease awareness for correlation between nyctophobia and hyposmia in individuals with COVID-19.
MethodsThis 52-year-old woman presented with sudden onset of loss of smell and taste with COVID-19, which returned to 85% of normal. Five months prior to presentation she was reinfected with COVID-19, and her smell and taste dropped to 20-50% of normal which improved. However, her symptoms worsened when she would lie down, to 30% of normal, but would improve with standing, moving and sitting. Even reclining for a short nap caused her sense of smell to drop, requiring her to stand for hours before her sense of smell would return leading to her nyctophobia that forced her to move around all the time. She altered her lifestyle and assiduously avoided lying down. When so overwhelmed by tiredness she would sleep sitting up. Prior to her chemosensory problems she slept well without any fear of lying down or sleeping.
ResultsPsychiatric exam: speech: coherent, relevant without circumstantiality, normal pace and volume. Mood: normal. Oriented x 3. Able to remember 7 digits forward and 5 backwards. Able to recall 3/4 objects without reinforcement. Interpretation of similarities: normal. Proverbs: normal. Calculation: normal. Neuropsychiatric testing: Clock Drawing Test: 4/4 (normal). Animal Fluency Test: 22 (normal).
ConclusionsNyctophobia, fear of positional dependent loss of smell, highlights the importance of smell to narcissistic perception of self. More than just one of senses, olfaction is important for mood regulation, memories and quality of life. Associated with chemosensory dysfunction, this is associated with 96% incidence of DSM-IIIR Axis I or II diagnoses, with the most common Axis I diagnosis being generalized anxiety disorder and dysthymia (Hirsch, 1996). This can be understood that the olfactory lobe is anatomically part of limbic system (MacLean, 1973). Smell fascilitates socialisation as well as maintaining interelationships; sexual dysfunctioning is seen in 17% of the population with olfactory loss (Hirsch, 1998). Deposition of memory engrams are facilitated as manifest with olfactory evoked nostalgia seen in 84% of the general population (Hirsch, 1992). Quality of life is reduced in 68% of patients who demonstrate smell loss (Deems, 1991). The importance of smell is thus intrinsic to an individual’s wellbeing, and the threat of loss of such sensation with change in position with sleep, was the precipitating event leading to nyctophobia in this subject. Assessing for fear of loss of smell in those with nyctophobia, especially with past COVID-19 infection, allows for increased understanding of etiology and indicates potential treatment approaches.
Disclosure of InterestNone Declared
Trajectories of depression and anxiety symptom severity during psychological therapy for common mental health problems
- Megan Skelton, Ewan Carr, Joshua E. J. Buckman, Molly R. Davies, Kimberley A. Goldsmith, Colette R. Hirsch, Alicia J. Peel, Christopher Rayner, Katharine A. Rimes, Rob Saunders, Janet Wingrove, Gerome Breen, Thalia C. Eley
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- Journal:
- Psychological Medicine / Volume 53 / Issue 13 / October 2023
- Published online by Cambridge University Press:
- 13 December 2022, pp. 6183-6193
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Background
There is substantial variation in patient symptoms following psychological therapy for depression and anxiety. However, reliance on endpoint outcomes ignores additional interindividual variation during therapy. Knowing a patient's likely symptom trajectories could guide clinical decisions. We aimed to identify latent classes of patients with similar symptom trajectories over the course of psychological therapy and explore associations between baseline variables and trajectory class.
MethodsPatients received high-intensity psychological treatment for common mental health problems at National Health Service Improving Access to Psychological Therapies services in South London (N = 16 258). To identify trajectories, we performed growth mixture modelling of depression and anxiety symptoms over 11 sessions. We then ran multinomial regressions to identify baseline variables associated with trajectory class membership.
ResultsTrajectories of depression and anxiety symptoms were highly similar and best modelled by four classes. Three classes started with moderate-severe symptoms and showed (1) no change, (2) gradual improvement, and (3) fast improvement. A final class (4) showed initially mild symptoms and minimal improvement. Within the moderate-severe baseline symptom classes, patients in the two showing improvement as opposed to no change tended not to be prescribed psychotropic medication or report a disability and were in employment. Patients showing fast improvement additionally reported lower baseline functional impairment on average.
ConclusionsMultiple trajectory classes of depression and anxiety symptoms were associated with baseline characteristics. Identifying the most likely trajectory for a patient at the start of treatment could inform decisions about the suitability and continuation of therapy, ultimately improving patient outcomes.
Different trajectories of depression, anxiety and anhedonia symptoms in the first 12 months of the COVID-19 pandemic in a UK longitudinal sample
- Christine E. Parsons, Kirstin L. Purves, Megan Skelton, Alicia J. Peel, Molly R. Davies, Fruhling Rijsdijk, Shannon Bristow, Thalia C. Eley, Gerome Breen, Colette R. Hirsch, Katherine S. Young
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- Psychological Medicine / Volume 53 / Issue 14 / October 2023
- Published online by Cambridge University Press:
- 05 December 2022, pp. 6524-6534
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Background
While studies from the start of the COVID-19 pandemic have described initial negative effects on mental health and exacerbating mental health inequalities, longer-term studies are only now emerging.
MethodIn total, 34 465 individuals in the UK completed online questionnaires and were re-contacted over the first 12 months of the pandemic. We used growth mixture modelling to identify trajectories of depression, anxiety and anhedonia symptoms using the 12-month data. We identified sociodemographic predictors of trajectory class membership using multinomial regression models.
ResultsMost participants had consistently low symptoms of depression or anxiety over the year of assessments (60%, 69% respectively), and a minority had consistently high symptoms (10%, 15%). We also identified participants who appeared to show improvements in symptoms as the pandemic progressed, and others who showed the opposite pattern, marked symptom worsening, until the second national lockdown. Unexpectedly, most participants showed stable low positive affect, indicating anhedonia, throughout the 12-month period. From regression analyses, younger age, reporting a previous mental health diagnosis, non-binary, or self-defined gender, and an unemployed or a student status were significantly associated with membership of the stable high symptom groups for depression and anxiety.
ConclusionsWhile most participants showed little change in their depression and anxiety symptoms across the first year of the pandemic, we highlight the divergent responses of subgroups of participants, who fared both better and worse around national lockdowns. We confirm that previously identified predictors of negative outcomes in the first months of the pandemic also predict negative outcomes over a 12-month period.
Depression, anxiety and PTSD symptoms before and during the COVID-19 pandemic in the UK
- K. S. Young, K. L. Purves, C. Hübel, M. R. Davies, K. N. Thompson, S. Bristow, G. Krebs, A. Danese, C. Hirsch, C. E. Parsons, E. Vassos, B. N. Adey, S. Bright, L. Hegemann, Y. T. Lee, G. Kalsi, D. Monssen, J. Mundy, A. J. Peel, C. Rayner, H. C. Rogers, A. ter Kuile, C. Ward, K. York, Y. Lin, A. B. Palmos, U. Schmidt, D. Veale, T. R. Nicholson, T. A. Pollak, S. A. M. Stevelink, T. Moukhtarian, A. R. Martineau, H. Holt, B. Maughan, A. Al-Chalabi, K. Ray Chaudhuri, M. P. Richardson, J. R. Bradley, P. F. Chinnery, N. Kingston, S. Papadia, K. E. Stirrups, R. Linger, M. Hotopf, T. C. Eley, G. Breen
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- Journal:
- Psychological Medicine / Volume 53 / Issue 12 / September 2023
- Published online by Cambridge University Press:
- 26 July 2022, pp. 5428-5441
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Background
The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors.
MethodOnline questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change.
ResultsProspective symptom analyses showed small decreases in depression (PHQ-9: −0.43 points) and anxiety [generalised anxiety disorder scale – 7 items (GAD)-7: −0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status.
ConclusionsWe highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.
P.012 The new-onset refractory status epilepticus (NORSE/FIRES) family registry
- K Kazazian, N Gaspard, LJ Hirsch, M Kellogg, SE Hocker, N Wong, R Farias-Moeller, K Eschbach, TE Gofton
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- Journal:
- Canadian Journal of Neurological Sciences / Volume 49 / Issue s1 / June 2022
- Published online by Cambridge University Press:
- 24 June 2022, p. S10
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Background: New-onset refractory status epilepticus (NORSE) is a rare clinical presentation affecting previously healthy individuals. Febrile infection-related epilepsy syndrome (FIRES) is a subcategory of NORSE and applies when a preceding fever occurs. The NORSE/FIRES Family Registry has been developed to gain insight into risk factors and to assess the spectrum of clinical outcomes amongst survivors. Methods: Survivors, surrogates, and physicians can enter patient data into the REDCap-based registry: https://www.norseinstitute.org/norse-registry-2. Information collected includes medical history, clinical presentation, and quality of life, among others. Participants are invited to complete follow-up surveys for up to two years following presentation of seizures. Enrollment is ongoing in multiple languages. Results: 56 participants are enrolled from 12 countries (2-78 years, median: 12.5, IQR: 20.5, 31 survivors). At ≥6 months after onset, survivors experience a mean of ≥12 seizures per month and remain on a median of 4 (IQR: 3) anti-seizure medications. The median quality of life amongst all survivors was rated 4/10 (IQR: 3.5). Conclusions: Preliminary data suggests that survivors of NORSE/FIRES have a high seizure burden and poor quality of life. This international multi-lingual family registry will help develop hypotheses for future studies and provides an opportunity for families to contribute to the scientific understanding of this disease.
These Are Not the Droids You Are Looking For: Mechanical Variant of Cotard’s Syndrome
- Ahmed A. Chaudhry, Syeda A. Shah, Alan R. Hirsch
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- CNS Spectrums / Volume 27 / Issue 2 / April 2022
- Published online by Cambridge University Press:
- 28 April 2022, p. 228
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Introduction
Cotard’s syndrome is a nihilistic delusion where the individual believes they are dead, partly dead, or replaced by an animal. The delusion that their body has been replaced by a purely inanimate azooic (but physical entity), such as a robot or a droid, has not hitherto been described.
MethodsCase study: This 60-year-old, right-handed, female, with a past history of schizophrenia presented with complaints of depression, irritability, and anger. When confronted with commitment papers signed by her father, she denied their truthfulness, insisting that he had been replaced by an imposter. This belief persisted unabated, despite treatment with 20 mg of haloperidol per day. Over time, she expressed the belief that she had been replaced by another person, whom she refused to identify. The following day she refused all food and water proclaiming that she had died and been replaced by a machine revealing, “I am not her. I am a robot.” Soon thereafter she developed tremulousness, stiffness, and rigidity. After haloperidol was decreased and benztropine started, these parkinsonism symptoms subsided, but her delusions persisted.
ResultsAbnormalities in physical examination: General: decreased blink frequency. Neurologic examination: Mental status examination: bradyphrenia, hypoverbal, blunted affect. Oriented ×2. Motor examination: bradykinetic, cogwheel rigidity in both upper extremities. Gait examination: slow shuffling gait, reduced bilateral arm swing. Cerebellar examination: resting tremor in both upper extremities at 3 cycles per second. Other: EEG: focal sharp transients in the left temporal region. MRI with and without contrast: normal. Toxicological, metabolic, endocrine screening: normal.
ConclusionThis illustrated sequential presentations of three delusions of misidentification. Upon presentation, she exhibited Capgras syndrome, the delusional belief that a familiar person has been replaced by a double. The nidus for this may have been the discovery that her father had signed her commitment papers. This was followed by the belief she was a double of herself, which is the syndrome of Reverse Subjective Doubles. Finally, she manifested Cotard’s syndrome in a previously undescribed manner, believing she had died and become a robot. Cotard’s and Capgras syndromes are known to present sequentially rather than concurrently, whereas the patient presented concurrently with all three syndromes. Drug-induced parkinsonism may have made the patient subjectively feel stiff, which she interpreted as being rigid like a robot. She was bradykinetic, did not eat or drink, and had rigidity, suggesting that these were somatic manifestations of her underlying delusion of being a robot or alternatively, may have been the somatic nidus for the delusion. Those who present with Cotard’s syndrome warrant evaluation for underlying medical conditions, serving as a substrate for this delusion.
FundingNo funding
Alliaceous Axilla as a Manifestation of Olfactory Reference Syndrome
- Anton S. Lima, Jenish V. Patel, Tiffany Chang, Alan R. Hirsch
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- CNS Spectrums / Volume 27 / Issue 2 / April 2022
- Published online by Cambridge University Press:
- 28 April 2022, p. 231
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Introduction
Olfactory reference syndrome (ORS) is a delusion in which a person believes that he or she exudes a displeasing body aroma that others perceive negatively. The axilla has been reported as a single primary source in only one patient. Furthermore, ORS is rarely reported to be associated with food odor. In these instances, the food is not edible. Delusions of ORS presenting as alliaceous edible food aromas have not heretofore been described.
Case ReportOne week after undergoing catheter ablation for atrial fibrillation, this 42-year-old right-handed male experienced a sudden onset of loss of smell and taste. This has persisted on presentation and he described a complete lack of smell, only being able to smell different spices and herbs. Over time, his sense of smell selectively improved such that he was able to smell alliaceous substances, including onion and garlic, as well as a few other aromas. At the same time his smell returned, he noted that his own body exuded a smell of garlic. This occurred especially while weightlifting at the gym. He noticed that the shirts he had worn working out, in the axillary regions, were encumbered with a garlic/onion miasma. He was fearful that this mephitic aroma was being secreted through his armpits, and that others would recognize his tragomaschalia. As a result, he restricted his activities. Over a few months, his smell ability gradually worsened back to the condition he was in after the ablation. Coincident with this, his perception that he was exuding an alliaceous aroma resolved.
ResultsMotor examination: Drift testing: mild left pronator drift. Left abductor digiti minimal sign. Olfactory testing prior to the development of ORS: Alcohol Sniff Test (AST): 0 (anosmia). Brief Smell Identification Test (B-SIT): 3 (anosmia). Olfactory testing during ORS: AST: 16 (hyposmia). B-SIT: 9 (hyposmia). Olfactory testing after resolution of ORS: AST: 0 (anosmia).
DiscussionThis could be explained by a physiologic axillary odor or malodor, which he could not detect before or after the ORS. During the ORS, the odor may have been misperceived in a dysosmic manner due to his underlying olfactory deficit. Such dysosmia may have then been interpreted as the aroma of an alliaceous vegetable. The intensity of the aroma may have been greatest at the axillary area if compared to the other sources, but due to his underlying hyposmia, he was able to perceive only the axilla as a sole source of the aroma. Besides, psychodynamic preoccupation with bodily physique may have explained his hypersensitivity to minor flaws and his excessive preoccupation with possible harassment from others. He may have consequently misinterpreted individuals’ benign observations and attitudes to presume the presence of aroma. In individuals with olfactory deficit, this investigation for the presence of ORS with traditionally unpleasant food aromas or the presence of ORS in those with chemosensory dysfunction is warranted.
FundingNo funding
The validation of contemporary body composition methods in various races and ethnicities
- Malia N. M. Blue, Katie R. Hirsch, Gabrielle J. Brewer, Hannah E. Cabre, Lacey M. Gould, Grant M. Tinsley, Bennett K. Ng, Eric D. Ryan, Darin Padua, Abbie E. Smith-Ryan
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- Journal:
- British Journal of Nutrition / Volume 128 / Issue 12 / 28 December 2022
- Published online by Cambridge University Press:
- 03 February 2022, pp. 2387-2397
- Print publication:
- 28 December 2022
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Few investigations have evaluated the validity of current body composition technology among racially and ethnically diverse populations. This study assessed the validity of common body composition methods in a multi-ethnic sample stratified by race and ethnicity. One hundred and ten individuals (55 % female, age: 26·5 (sd 6·9) years) identifying as Asian, African American/Black, Caucasian/White, Hispanic, Multi-racial and Native American were enrolled. Seven body composition models (dual-energy X-ray absorptiometry (DXA), air displacement plethysmography (ADP), two bioelectrical impedance devices (BIS, IB) and three multi-compartment models) were evaluated against a four-compartment criterion model by assessing total error (TE) and standard error of the estimate. For the total sample, measures of % fat and fat-free mass (FFM) from multi-compartment models were all excellent to ideal (% fat: TE = 0·94–2·37 %; FFM: TE = 0·72–1·78 kg) compared with the criterion. % fat measures were very good to excellent for DXA, ADP and IB (TE = 2·52–2·89 %) and fairly good for BIS (TE = 4·12 %). For FFM, single device estimates were good (BIS; TE = 3·12 kg) to ideal (DXA, ADP, IB; TE = 1·21–2·15 kg). Results did not vary meaningfully between each race and ethnicity, except BIS was not valid for African American/Black, Caucasian/White and Multi-racial participants for % fat (TE = 4·3–4·9 %). The multi-compartment models evaluated can be utilised in a multi-ethnic sample and in each individual race and ethnicity to obtain highly valid results for % fat and FFM. Estimates from DXA, ADP and IB were also valid. The BIS may demonstrate greater TE for all racial and ethnic cohorts and results should be interpreted cautiously.
Opportunities for antibiotic stewardship in emergency department or hospitalized patients with asymptomatic bacteriuria: identifying risk factors for antibiotic treatment
- Morgan L. Bixby, Brian R. Raux, Aakansha Bhalla, Christopher McCoy, Elizabeth B. Hirsch
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- Journal:
- Antimicrobial Stewardship & Healthcare Epidemiology / Volume 2 / Issue 1 / 2022
- Published online by Cambridge University Press:
- 31 January 2022, e16
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Antibiotic treatment of asymptomatic bacteriuria (ASB) is considered inappropriate and may lead to adverse events. This 2-center, retrospective cohort study including emergency department or inpatient adults identified pyuria (odds ratio, 2.43; 95% confidence interval, 1.17–5.01; P = .02) as the only independent risk factor for antibiotic treatment of ASB.
Fostering Tobacco Regulatory Team Science through a multisite, virtual fellowship program for early-career researchers
- Tinuola B. Ajayi, Ellen Childs, Christy Di Frances Remein, Leigh R. Forbush, Justin B. Ragasa, Jessica L. Fetterman, Glenn A. Hirsch, Emelia J. Benjamin
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- Journal:
- Journal of Clinical and Translational Science / Volume 6 / Issue 1 / 2022
- Published online by Cambridge University Press:
- 04 January 2022, e14
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Introduction:
In an era of complex, multi-institutional, team-based science, there is little guidance for the successful creation of effective, collaborative, multisite training programs.
Objective:We designed, implemented, and evaluated a multi-institutional Tobacco Regulatory Science (TRS) fellowship representing a scalable program that may be customized for other research areas.
Methods:Using a mixed-methods approach, we analyzed program evaluations from trainees enrolled in the first 7 years of the American Heart Association (AHA) Tobacco Regulation and Addiction Center (A-TRAC) fellowship (2014–2021). We also reported the program outcomes, including published TRS manuscripts, independent grant funding, Food and Drug Administration (FDA) Docket comments submitted on TRS topics, TRS oral and poster presentations, research awards, and promotions in the TRS field.
Results:Thirty-five unique trainees (49% [n = 17] female, 29% [n = 10] Black) from eight institutions within the A-TRAC network participated in the fellowship since its inception. The trainees reported 74 TRS publications, 78 TRS oral or poster presentations, 25 FDA Docket comment submissions, and 13 funded grant awards. Participant evaluations indicated six areas of programmatic strength: 1) blended instruction medium with webinars and in-person meetings, 2) curricular emphasis on theories of experiential learning, 3) focus on career and professional development, 4) integrated mentorship model, 5) culture of feedback and feedforward to foster successful learning, and 6) focus on recruiting diverse participants. The A-TRAC model stresses experiential education, feedback and feedforward, and peer learning.
Conclusions:Our resource-effective, needs-driven program is a reproducible model for institutions interested in developing multisite, virtual research education programs in the era of team science.
Acute feeding has minimal effect on the validity of body composition and metabolic measures: dual-energy X-ray absorptiometry and a multi-compartment model
- Abbie E. Smith-Ryan, Gabrielle Brewer, Lacey M. Gould, Malia N.M. Blue, Katie R. Hirsch, Casey E. Greenwalt, Courtney Harrison, Hannah E. Cabre, Eric D. Ryan
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- Journal:
- British Journal of Nutrition / Volume 128 / Issue 2 / 28 July 2022
- Published online by Cambridge University Press:
- 16 August 2021, pp. 311-323
- Print publication:
- 28 July 2022
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Understanding the effects of acute feeding on body composition and metabolic measures is essential to the translational component and practical application of measurement and clinical use. To investigate the influence of acute feeding on the validity of dual-energy X-ray absorptiometry (DXA), a four-compartment model (4C) and indirect calorimetry metabolic outcomes, thirty-nine healthy young adults (n 19 females; age: 21·8 (sd 3·1) years, weight; 71·5 (sd 10·0) kg) participated in a randomised cross-over study. Subjects were provided one of four randomised meals on separate occasions (high carbohydrate, high protein, ad libitum or fasted baseline) prior to body composition and metabolic assessments. Regardless of macronutrient content, acute feeding increased DXA percent body fat (%fat) for the total sample and females (average constant error (CE):–0·30 %; total error (TE): 2·34 %), although not significant (P = 0·062); the error in males was minimal (CE: 0·11 %; TE: 0·86 %). DXA fat mass (CE: 0·26 kg; TE: 0·75 kg) and lean mass (LM) (CE: 0·83 kg; TE: 1·23 kg) were not altered beyond measurement error for the total sample. 4C %fat was significantly impacted from all acute feedings (avg CE: 0·46 %; TE: 3·7 %). 4C fat mass (CE: 0·71 kg; TE: 3·38 kg) and fat-free mass (CE: 0·55 kg; TE: 3·05 kg) exceeded measurement error for the total sample. RMR was increased for each feeding condition (TE: 1666·9 kJ/d; 398 kcal/d). Standard pre-testing fasting guidelines may be important when evaluating DXA and 4C %fat, whereas additional DXA variables (fat mass and LM) may not be significantly impacted by an acute meal. Measuring body composition via DXA under less stringent pre-testing guidelines may be valid and increase feasibility of testing in clinical settings.
108 Warning: Generic Suboxone Not Equal to Name Brand
- Arvind Datt, Alan R. Hirsch
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- CNS Spectrums / Volume 25 / Issue 2 / April 2020
- Published online by Cambridge University Press:
- 24 April 2020, p. 270
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Introduction:
On June 14, 2018, the FDA approved generic buprenorphine/naloxone, as an alternative to the brand Suboxone (FDA,2018). A patient who developed acute withdrawal symptoms when switched from Suboxone to generic buprenorphine/naloxone at the same dosage, with resolution with replacement with brand name Suboxone, is presented. Induction of withdrawal with generic buprenorphine/naloxone has not heretofore been described.
Methods:Case Study: A 39-year-old right handed single male presented with a past medical history of intravenous heroin dependence. He was relapse free for 5 years and without change on Suboxone film 8mg/2mg twice daily, and was provided with prescriptions for the same, which was substituted to generic brand Dr. Reddy’s Lab SA buprenorphine HCl/naloxone HCl 8mg/2mg film. After two days on this, one hour after taking generic buprenorphine/naloxone film, symptoms of withdrawal began as manifest by hot flashes, diaphoresis, cold chills, leg cramping, and nausea without vomiting. These were the same symptoms he experienced during his past inpatient withdrawal from opioids. These symptoms recurred every day for an entire week until switching back to brand name Suboxone, whereupon his withdrawal symptoms resolved.
Discussion:The mechanism whereby the generic buprenorphine/naloxone combination induced withdrawal symptoms is unclear. It appears that this generic version was either not effectively blocking the mu receptors or the naloxone was inducing a withdrawal state. Possibly the porous nature of the film was such that less of the buprenorphine was absorbed through the mucosa. As a result, less was transferred into the bloodstream, across the blood brain barrier, to the nucleus accumbens, and ultimately on kappa opioid/mu receptor (Centerwatch, 2002). Alternatively, a greater amount of naloxone may have been absorbed transmucosally, thus inducing withdrawal. The absorption may have been normal, but the exact milligram dosage may not be accurate with either too little buprenorphine or too much naloxone. On the other hand, this buprenorphine compound may have been pH sensitive, such that it became inactivated upon exposure to the mildly acidic salivary pH. He could have been malingering this response. Again this is unlikely since he was not given a higher dose of buprenorphine/naloxone, rather the same dose of Suboxone as previously prescribed. It is important that physicians be aware of the possibility for acute withdrawal and increased cravings, which can lead to relapse while using this agent. Further investigation of the efficacy of the generic variant and Suboxone as replacement therapy is warranted.
101 Amyotrophic Lateral Sclerosis (ALS) - Not Just a Motor Disease? Isolated Bitter and Sweet Taste Loss in ALS
- Ahmed A Ashary, Dev N Patel, Alan R Hirsch
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- CNS Spectrums / Volume 25 / Issue 2 / April 2020
- Published online by Cambridge University Press:
- 24 April 2020, p. 266
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Study Objective:
Specific taste quality deficits in ALS has not heretofore been described.
METHOD:Case Study: A 71 year old right handed female presented with a two year course of progressive reduction in strength in her hands, arms and legs with difficulty tying shoe laces, opening jars, writing and walking. She described nocturnal muscle spasms involving all extremities. Gradually, over eight months prior to presentation, all food began to taste bad and horribly bitter. Associated with no appetite and a seven pounds weight loss.
RESULTS:Abnormalities in Neurological examination: Cranial Nerve (CN) examination: CN IX and X: Gag absent bilaterally. Motor examination: Bulk: atrophy in thenar and hypothenar eminences and intrinsics in both upper extremities. Percussion induced fasciculation and myotonia in both shoulders and arms. Fasciculation of tongue with percussion myotonia of tongue. Strength: Intrinsic 4/5 in both upper extremities, 3/5 in abductor policis brevis bilaterally, 3/5 right gastrocnemius soleus, 4/5 bilateral anterior tibialis. Drift testing: left abductor digiti minimi sign. Gait: Heel and toe walking unstable with circumduction of left leg. Tandem gait unstable. Cerebellar: Holmes rebound phenomena positive in the left upper extremity. Deep tendon reflexes: 1+ left brachioradialis. 1+ left triceps. 3+ right ankle jerks. 0 left ankle jerk. Positive jaw jerk. Chemosensory Testing: Normosmia to: Alcohol Sniff Test (46), Pocket Smell Test (3/3) and Retronasal Smell Index (9). Taste Quadrant Testing: ageusia in the palate to sodium chloride and citric acid. Ageusia throughout the palate, tongue and whole mouth to sucrose and quinine hydrochloride. Fungiform papillae count: left 18, right 20 (normal). Lip biopsy (normal). MRI: T2 flair in bilateral corticospinal tracts, left greater than right in the spinal cord and the brain. EMG: fibrillation, positive waves with fasciculation in all four extremities. Voluntary contraction with polyphasic unstable motor unit action potentials.
CONCLUSION:While Lang found no taste loss in ALS (Lang, 2011), Pelletier found reduction in intensity of taste to all modalities in different sectors of the tongue, but paradoxically demonstrated normogeusia in whole mouth taste perception (Pelletier, 2013). Pathological specimens of those with ALS revealed degeneration in the nucleus parabrachialis medialis and tractus trigeminothalamicus dorsalis (Oyanagi, 2015), suggesting that taste deficit may be due to central white matter abnormalities. Sweet taste is localized in the most posterior and rostral aspect of the right insular cortex, immediately adjacent to bitter (Prinster, 2017), suggesting a neighborhood effect phenomena. Weight loss in ALS may be due to sensory distortion and secondary impairment of appetite. It would be worthwhile to investigate those with ALS for evidence of otherwise overlooked gustatory deficits, correction of which may improve appetite and nutritional state.
131 A Marionettist Pulling My Strings: A Case of Buprenorphine-induced Chorea
- Dev Patel, Ishandeep Gandhi, Faisal Malek, Camille Olechowski, Alan R. Hirsch
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- Journal:
- CNS Spectrums / Volume 25 / Issue 2 / April 2020
- Published online by Cambridge University Press:
- 24 April 2020, pp. 282-283
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Introduction:
Choreaform movements provoked by opiates is an infrequent adverse event. Buprenorphine induction of chorea has not heretofore been described. Such a case is presented.
METHOD:Case Study: A 38-year-old female presented with a decade long history of alcohol, cocaine, benzodiazepine, and heroin abuse. The patient was insufflating 1.5 grams of heroin daily. On presentation, she was actively withdrawing, scoring 17 on the Clinical Opioid Withdrawal Scale. Urine toxicology screening was positive for opiates, cocaine, and cannabinoids. Buprenorphine 4 mg sublingual was initiated. Within one hour, she observed, “My legs were moving uncontrollably as if I was a marionette.” These dance-like movements were isolated to both legs and gradually resolved after discontinuation of buprenorphine: most of the movements manifested in the first 8 hours, and dissipated over the next 2 days. She did have similar movements after treatment with quetiapine during a previous hospitalization, years earlier.
RESULTS:Abnormalities in physical examination: General: goiter, bilateral palmar erythema. Neurological examination: Cranial Nerve (CN) Examination: CN I: Alcohol Sniff Test: 2 (anosmia). Motor Examination: Drift testing: mild right pronator drift. Reflexes: 3+ bilateral lower extremities. Neuropsychiatric Examination: Clock Drawing Test: 3 (abnormal). Animal Fluency Test: 18 (normal). Go-No-Go Test 6/6 (normal).
DISCUSSION:Buprenorphine induced chorea could be a result of partial mu-opioid agonism, or kappa and delta receptor antagonism (Burke, 2018; Cowan, 1977). Mu-opioid receptor activation causes increased dopamine turnover in the nigrostriatum, which is responsible for locomotor sensitization (Campos-Jurado, 2017). With the addition of mu-opioid receptor modulation of dopamine release, kappa-opioid receptor alters various neurotransmitters in the basal ganglia, potentiating hyperkinetic movements. Buprenorphine’s choreiformogenic action may be due to kappa-opioid receptors ability to augment neurotransmission in the striatum (Escobar, 2017; Bonnet, 1998). The combination of simultaneous activity of these three opioid receptors may cause chorea, since they act to modulate dopamine, glutamate, and GABA in the direct and indirect pathways within the basal ganglia (Abin, 1989; Cui, 2013; Allouche, 2014; Trifilieff, 2013). This patient’s history of heroin and cocaine use may have caused supersensitization of dopamine receptors (Memo, 1981), provoking hyperkinesia. Involvement of substance-induced sensitization with concurrent kappa-opioid receptor neurotransmitter augmentation in direct and indirect pathways in the basal ganglia may have primed our patient to the development of chorea after buprenorphine administration. Further investigation for the presence of extrapyramidal movements in those undergoing buprenorphine treatment is warranted.
A preliminary investigation of schematic beliefs and unusual experiences in children
- D. Noone, C. Ames, N. Hassanali, S. Browning, K. Bracegirdle, R. Corrigall, K.R. Laurens, C.R. Hirsch, E. Kuipers, L. Maddox, D. Fowler, S. Jolley
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- Journal:
- European Psychiatry / Volume 30 / Issue 5 / July 2015
- Published online by Cambridge University Press:
- 15 April 2020, pp. 569-575
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Background
In cognitive models of adult psychosis, schematic beliefs about the self and others are important vulnerability and maintaining factors, and are therefore targets for psychological interventions. Schematic beliefs have not previously been investigated in children with distressing unusual, or psychotic-like, experiences (UEDs). The aim of this study was firstly to investigate whether a measure of schematic beliefs, originally designed for adults with psychosis, was suitable for children; and secondly, to examine the association of childhood schematic beliefs with internalising and externalising problems and with UEDs.
MethodSixty-seven children aged 8–14 years, with emotional and behavioural difficulties, completed measures of UEDs, internalising (depression and anxiety), and externalising (conduct and hyperactivity-inattention) problems, together with the Brief Core Schema Scales (BCSS).
ResultsThe BCSS was readily completed by participants, and scale psychometric properties were good. Children tended to view themselves and others positively. Internalising and externalising problems and UEDs were all associated with negative schematic beliefs; effect sizes were small to medium.
ConclusionsSchematic beliefs in young people can be measured using the BCSS, and negative schematic beliefs are associated with childhood psychopathology and with UEDs. Schematic beliefs may therefore form a useful target in psychological interventions for young people with UEDs.
Trainee self-assessment of cognitive behaviour therapy competence during and after training
- Sarah Beale, Sheena Liness, Colette R. Hirsch
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- Journal:
- The Cognitive Behaviour Therapist / Volume 13 / 2020
- Published online by Cambridge University Press:
- 22 January 2020, e1
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Large-scale cognitive behavioural therapy (CBT) training and implementation programmes, such as the pioneering Improving Access to Psychological Therapies (IAPT) initiative in the UK, aim to develop a workforce of competent therapists who can deliver evidence-based interventions skilfully. Self-awareness of competence enables CBT therapists to accurately evaluate their clinical practice and determine professional development needs. The accuracy of self-assessed competence, however, remains unclear when compared with assessments conducted by markers with expertise in CBT practice and evaluation. This study investigated the relationship between self- and expert-rated competence – assessed via therapy recordings rated on the Cognitive Therapy Scale Revised (CTS-R) scale – for a large sample of IAPT CBT trainees during training and, for the first time, at post-training follow-up. CBT trainees (n = 150) submitted therapy recordings at baseline, mid-training and end-of-training. At 12+ month follow-up, a subset of former trainees (n = 30) submitted recordings from clinical practice. There were positive relationships (r = .27 to .56) between self and expert CTS-R scores at all time points. The proportion of tapes demonstrating significant agreement between self and expert ratings (CTS-R difference <5 points) increased significantly across training and remained stable at follow-up. Findings indicate that accurate self-awareness of competence can be developed during structured CBT training and retained in the workplace. These outcomes are encouraging given the importance of self-awareness to CBT practice and accreditation. Future investigation into the development and maintenance of accurate self-awareness of competence is warranted.
Key learning aims(1) What is the relationship between self-ratings and expert ratings of CBT competence during training and at post-training follow-up?
(2) Does agreement between self and expert competence ratings improve with CBT training?
(3) How does agreement between self and expert ratings change across training for more- and less-competent trainees?
(4) Can accurate self-awareness of competence be retained post-training in the workplace?
Multi-professional IAPT CBT training: clinical competence and patient outcomes
- Sheena Liness, Sarah Beale, Susan Lea, Suzanne Byrne, Colette R. Hirsch, David M. Clark
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- Journal:
- Behavioural and Cognitive Psychotherapy / Volume 47 / Issue 6 / November 2019
- Published online by Cambridge University Press:
- 28 March 2019, pp. 672-685
- Print publication:
- November 2019
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Background:
There is international interest in the training of psychological therapists to deliver evidence-based treatment for common mental health problems. The UK Improving Access to Psychological Therapies (IAPT) programme, one of the largest training initiatives, relies on competent therapists to successfully deliver cognitive behaviour therapy (CBT) and promote good patient outcome.
Aims:To evaluate an IAPT CBT training course by assessing if trainees’ clinical skills improve during training and reach competency standards, and to report patient outcome for submitted training cases. To investigate a possible relationship between trainee competence and patient outcome. To explore professional differences during training.
Method:CBT trainee (n = 252) competence was assessed via audio recordings of therapy sessions at the beginning, middle and end of training. Patient pre- to post-treatment outcomes were extracted from submitted training cases (n = 1927). Differences in professional background were examined across competence, academic final grade and tutorial support.
Results:CBT trainees attained competence by the end of the course with 77% (anxiety recordings) and 72% (depression recordings) improving reliably. Training cases reported pre- to post-treatment effect sizes of 1.08–2.26 across disorders. CBT competence predicted a small variance in clinical outcome for depression cases. Differences in professional background emerged, with clinical psychologists demonstrating greater competence and higher academic grades. Trainees without a core professional background required more additional support to achieve competence.
Conclusions:Part of a new CBT therapist workforce was successfully trained to deliver relatively brief treatment effectively. Trainees without a core profession can be successfully trained to competence, but may need additional support. This has implications for workforce training.
2 What’s Bugging You? Alliaceous Therapy for Ekbom Syndrome
- Fizah S. Chaudhary, Jasir T. Nayati, Ather M. Ali, Alan R. Hirsch
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- Journal:
- CNS Spectrums / Volume 24 / Issue 1 / February 2019
- Published online by Cambridge University Press:
- 12 March 2019, pp. 175-176
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Study Objective
Delusional parasitosis, or Ekbom syndrome, is a fixed false belief of being infested by parasites [Bellanger 2009]. With easy accessibility of the internet, serving as a vital tool in acquiring myriad information, these delusions typically arise and can be fueled by external sources as self-research [Bell2005]. For instance, garlic (allium sativum) has been reported to exhibit anthelmintic activity against cestodes (tapeworms), proving to be a natural treatmentoption [Abdel-Ghaffar 2010]. Without proper instructions, guidelines, or control of such information, psychopathological manifestations may be derived.
MethodsA young adult male presented with severe psychosis. He reports responding to an internal stimuli, non-command auditory hallucinations, and paranoid ideations specifically in regards to his body and health for several weeks. Prior to presentation, he experienced abdominal pain and constipation for five days, but attributed it to the belief of having tapeworms. He stated that he researched cures for several days using the internet and found garlic as a treatment option. He attempted to alleviate his symptoms by ingested 197 pills of 1,000 milligram (mg) garlic supplements, two 100mg bisacodyl laxatives, and five 100mg docusate stool softeners in one day. He denies any suicidal/homicidal ideations, illicit substance abuse, deja-vu, and jamais-vu.
ResultsPsychiatric examination is as follows: Mental Status Examination: awake, alert, and oriented x3. General Appearance: disheveled. Speech: soft, mumbling, and minimally non-responsive. Psychomotor Activity: moderately sedated. Eye Contact: poor. Mood: dysphoric. Affect: flat. Thought Process: flight of ideas. Thought Content: preoccupied. Judgement/Insight: poor. Immediate/Recent Recall: poor. Remote Memory: poor.
ConclusionDelusional parasitosis and somatic parasitic infestation has dire consequences in which one's health can become compromised. For those suffering from parasitosis, addition of garlic in food as well as garlic supplements of 50mg/kg body weight has been reported as a possible naturopathic treatment option in Cryptosporidiosis and Schistosoma mansoni [Gaafar 2012; Nahed 2009]. In addition, it was found that a dose of 1.2mg for three days was efficient, safe, and shortens the duration of treatment for parasites [Soffar 1991]. However, this patient ingested 197,000mg of garlic supplements without experiencing symptoms of overdose. This may include burning sensation of the mouth or stomach, flatulence, nausea/vomiting, diarrhea, thrombocytopenia, and anaphylaxis [Bayan 2014]. The efficacy of garlic for treatment of true parasitosis is unknown, but can be found in common practice especially those who practice naturopathic medicine. In this case, it is unlikely to have a positive effect, especially when delusional in nature. The use of homeopathic medication in those with true parasitosis and delusional parasitosis should be queried.
Funding Acknowledgements: Smell & Taste Treatment and Research Foundation
61 Heroin Dependence as an Enantiopathy to Quetiapine-Induced Restless Leg Syndrome
- Emma Moghaddam, Edward Lichtenshtein, Sima Patel, Nikhil Rana, Rohan Rana, Alan R. Hirsch
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- Journal:
- CNS Spectrums / Volume 24 / Issue 1 / February 2019
- Published online by Cambridge University Press:
- 12 March 2019, p. 207
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Introduction
Use of heroin in self-management of Restless Leg Syndrome (RLS) has not heretofore been described. Such a case is presented.
MethodsCase study: This 29 years old right handed male presented with a long history of major depressive disorder, generalized anxiety disorder and opioid dependence. The Patient felt compelled to take quetiapine since was the only drug found to be effective in controlling racing thoughts, Major Depressive Disorder with psychotic features. Prior to use of quetiapine the patient never experienced RLS. Quetiapine in doses ranging from 25mg to 300mg a day precipitated severe RLS whereby he was forced to move his leg all night long leading to poor sleep quality. The RLS was unresponsive to Gabapentin and Benztropine, however it was eliminated with a variety of opioids including hydrocodone, buprenorphine, buprenorphine/naloxone. Particularly sensitive to heroin, 1/2 twenty dollar bag, self-administered IV prior to sleep eliminated the RLS immediately, but when injected more than four hours before sleep it had no effect. RLS acted only when induced with quetiapine, since he wished to continue quetiapine to control his mood, he felt compelled to self-medicate with heroin to stop RLS side effects. He showed no other signs of extrapyramidal symptomatology or evidence of any other movement disorder.
ResultsAbnormalities in physical examination: General: Abundance of tattoos on body and face. Cranial Nerve (CN): CN I: Alcohol Sniff Test: 7cm (anosmia). CN II: Anisocoria OD 5mm OS 2mm. Motor Examination: drift testing: right pronator drift. Cerebellar: Finger to Nose: end point dysmetria bilaterally. Low amplitude high frequency tremor in both upper extremities on extension. Sensory Examination: decreased graphesthesia in both upper extremities. Reflexes: 3+ knee jerks, absent ankle jerks, positive jaw jerk, bilateral palmomental reflex is present.
DiscussionThis patient has a long history of quetiapine use due to his major depressive disorder with psychotic features and subsequent self-administration of IV heroin reportedly to reduce the symptoms of quetiapine-induced RLS. Heroin elevates dopamine levels in forebrain by blocking inhibitory GABA interneurons near the ventral tegmental area, leading to activation of mesocorticolimbic dopaminergic neurons (Nakagawa 2008, Steidl 2011). The time frame of opioid administration has a critical impact on its efficacy in improving RLS symptoms. However, the drug’s effects only up to 3 to 6hours (Buchfuhrer 2012). In this case administration of heroin more than 4hours before sleep would not alleviate the RLS symptoms. Patient chose the time of injection, not for hedonic pleasure of heroin, but rather to prevent RLS symptoms. In those with heroin dependence, the possibility that is a result of self-medication of underlying movement disorder warrants additional investigation. In those with RLS who are unresponsive to other treatment modalities, a trial of opioids maybe worthwhile.