Relationship of psychotropic medication use with physical function among postmenopausal women.

To examine cross-sectional and longitudinal relationships of psychotropic medications with physical function after menopause. Analyses involved 4557 Women's Health Initiative Long Life Study (WHI-LLS) participants (mean age at WHI enrollment (1993-1998): 62.8 years). Antidepressant, anxiolytic, and sedative/hypnotic medications were evaluated at WHI enrollment and 3-year follow-up visits. Performance-based physical function [Short Physical Performance Battery (SPPB)] was assessed at the 2012-2013 WHI-LLS visit. Self-reported physical function [RAND-36] was examined at WHI enrollment and the last available follow-up visit-an average of 22 [±2.8] (range: 12-27) years post-enrollment. Multivariable regression models controlled for socio-demographic, lifestyle, and health characteristics. Anxiolytics were not related to physical function. At WHI enrollment, antidepressant use was cross-sectionally related to worse self-reported physical function defined as a continuous (ß = -6.27, 95% confidence interval [CI]: -8.48, -4.07) or as a categorical (< 78 vs. ≥ 78) (odds ratio [OR] = 2.10, 95% CI: 1.48, 2.98) outcome. Antidepressant use at WHI enrollment was also associated with worse performance-based physical function (SPPB) [< 10 vs. ≥ 10] (OR = 1.53, 95% CI: 1.05, 2.21) at the 2012-2013 WHI-LLS visit. Compared to non-users, those using sedative/hypnotics at WHI enrollment but not at the 3-year follow-up visit reported a faster decline in physical function between WHI enrollment and follow-up visits. Among postmenopausal women, antidepressant use was cross-sectionally related to worse self-reported physical function, and with worse performance-based physical function after > 20 years of follow-up. Complex relationships found for hypnotic/sedatives were unexpected and necessitate further investigation.

Longitudinal association of allostatic load with depressive symptoms among urban adults: Healthy Aging in Neighborhoods of Diversity across the Life Span study.

BACKGROUND: Evidence suggests that lifetime exposure to stressful life events and chronic stressors may be linked to geriatric depression. Allostatic load (AL) is considered a mediator of the stress-health relationship and has been linked to psychosocial factors reflecting health disparities. The purpose of this study was to examine the longitudinal associations of AL with depressive symptoms scores among urban adults, before and after stratifying by sex and race. METHODS: Secondary analyses were performed using Visit 1 (2004-2009), Visit 2 (2009-2013) and Visit 3 (2013-2017) data collected on 2298 Healthy Aging in Neighborhoods of Diversity across the Life Span study participants (baseline age: 30-64 y). AL at Visit 1 (ALv1) and z-transformed probability of higher AL trajectory (ALtraj) between Visits 1 and 3 were calculated using cardiovascular, metabolic and inflammatory risk indicators. The 20-item Center for Epidemiologic Studies Depression (CES-D) scale was used to calculate total and domain-specific depressive symptoms scores. Mixed-effects linear models controlled for socio-demographic, lifestyle and health characteristics. RESULTS: In fully adjusted models, a positive cross-sectional relationship was observed between ALv1 and "somatic complaints" depressive symptoms (ß = 0.21, P = 0.006) score at Visit 1, whereas ALtraj was associated with increasing depressive symptoms score (ß = 0.086, P = 0.003) between Visits 1 and 3. An inverse relationship was observed between ALtraj and "positive affect" depressive symptoms score at Visit 1 among women (ß = -0.31, P < 0.0001) and White adults (ß = -0.32, P = 0.004). Among women, ALtraj was also positively related to change in "somatic complaints" depressive symptoms score between Visits 1 and 3 (ß = 0.043, P = 0.020). CONCLUSIONS: Among urban adults, AL may be associated with "somatic complaints" depressive symptoms at baseline. Higher AL trajectories may predict increasing depressive symptoms (overall) and increasing "somatic complaints" depressive symptoms (among women). A higher AL trajectory may be associated with lower "positive affect" depressive symptoms at baseline among women and White adults only.

Trajectories in allostatic load as predictors of sleep quality among urban adults: Healthy aging in neighborhoods of diversity across the life span study.

OBJECTIVE: /Background: The allostatic framework is a theoretical perspective that identifies allostatic load (AL) as a meaningful measure of dysregulation and desynchrony across biological processes due to cumulative stress exposure, thereby increasing disease risk. Research exploring the relationships of AL with sleep quality have yielded inconsistent findings. We examined AL at three visits (2004-2009 [Visit 1], 2009-2013 [Visit 2] and 2013-2017 [Visit 3]) in relation to sleep quality [Visit 3] among urban adults by sex, race and age group. PATIENTS/METHODS: We analyzed data on 1489 Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) participants [59.6% female, baseline age: 48.2 years, 58.5% African Americans] with available data on cardiovascular, metabolic and inflammatory AL markers and Pittsburgh Sleep Quality Index (PSQI) scores. Least squares regression models were constructed to evaluate AL score at Visit 1 (ALv1) and z-transformed probability of higher trajectory in AL score between Visit 1 and Visit 3 (ALtraj) as predictors of PSQI score at Visit 3, controlling for demographic, lifestyle and health characteristics at Visit 1. ALtraj was generated using group-based trajectory modeling. RESULTS: In fully adjusted models, ALv1 and PSQI score were positively related among men only (ß = 0.43, P = 0.001), whereas higher ALtraj was associated with PSQI score among women (ß = 0.51, P = 0.001), White (ß = 0.45, P = 0.011) and African American (ß = 0.33, P = 0.014) populations. There were no statistically significant interactions according to age group (<50 vs. ≥ 50). CONCLUSIONS: Disparities exist whereby AL trajectory predicted sleep quality among women irrespective of race and baseline AL predicted sleep quality among men. Future studies should examine bi-directional AL-sleep relationships.

A Review of Clinical and Laboratory Predictors of Severe COVID-19 Disease.

INTRODUCTION: In late December 2019, the coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. It quickly spread and emerged as a global pandemic with far-reaching impacts on society. As clinical research on this novel virus emerges, there is a limited amount of data that review clinical and laboratory predictors of severe disease. We present a case of a patient with severely elevated inflammatory markers who remained clinically stable during his hospital course. CASE DISCUSSION: A 53-year-old male presented to the emergency room with 11 days of persistent fevers and new-onset anterior chest tightness. He was admitted to the hospital due to a reported oxygen desaturation at home to 87% (taken by his spouse, a healthcare professional) and ambulatory oxygen desaturation down to 87%. He was noted to have severely elevated inflammatory markers, lymphopenia, and computed tomography pulmonary angiograph findings consistent with COVID-19. He remained on room air and clinically stable throughout his 3-day hospital course. While his C-reactive protein levels improved, his ferritin and erythrocyte sedimentation rate continued to elevate. He was discharged home and was symptom-free within 4 days of hospital discharge. DISCUSSION: COVID-19 has proven to be a viral disease with a high transmission rate, that has caused over 100,000 deaths in the United States, thus far. The decision to admit a patient must balance the risks of transmission with the benefit of being readily available to provide urgent supportive care should the patient develop complications. Thus, there is a significant benefit to being able to predict poor outcomes. We performed a targeted review of the literature, focusing on clinical and laboratory predictors of poor outcomes in COVID-19. Our case report and narrative review outline these findings within the context of our case.

A Comprehensive, Multimodal, Interdisciplinary Approach to Chronic Non-Cancer Pain Management in a Family Medicine Clinic: A Retrospective Cohort Review.

INTRODUCTION: The complexity of chronic non-cancer pain in the setting of regulatory efforts to curb opioid usage presents a novel challenge for the medical community. Much of this burden falls on primary care clinics. We retrospectively quantified the reduction of opioid usage by patients in a multimodal, interdisciplinary, primary care clinic for chronic pain. METHODS: A multimodal, interdisciplinary, chronic pain clinic embedded in a large academic military family medicine clinic operated one-half day weekly to address referrals from within the clinic at large. Appointment times were longer than typical primary care appointments. The clinic was equipped with support staff, ancillary specialty providers, and non-pharmacologic complementary treatment resources. A retrospective cohort review was conducted on 78 patients referred to this clinic from March 1, 2015 (the inception date of the clinic) through December 31, 2015. RESULTS: Fifty-four of 78 patients met inclusion criteria. Overall mean morphine equivalent daily dosing (MEDD) dropped from 31.5 MEDD to 20.5 MEDD (p = 0.0005) 12 months post-intervention and from 31.5 MEDD to 9.5 MEDD (p < 0.0001) 36 months post-intervention. Four patients with a high mean baseline opioid dose of 185.2 MEDD dropped to 29.9 MEDD 36 months post-intervention. The mean 0-10 pain score decreased from 5.3 ± 2.2 to 4.0 ± 2.5 (p = 0.001). CONCLUSION: A multimodal, interdisciplinary, primary care-based, chronic pain clinic equipped with extended appointment times, non-pharmacologic treatment resources, and specialty access can curb opioid usage. Leadership support for protracted appointment duration, complementary treatment resources, and interdisciplinary personnel is crucial to success.

Isolated blunt pancreatic trauma: A benign injury?

BACKGROUND: Blunt pancreatic trauma is rare, and the reported mortality is high. The true outcomes in isolated pancreas trauma are not known, and the optimal management according to injury severity is controversial. The present study evaluated the incidence, outcomes, and optimal management of isolated blunt pancreatic injuries. METHODS: National Trauma Data Bank study, including patients with blunt pancreatic trauma. Patients with major associated injuries or other severe intra-abdominal injuries were excluded. Patients' demographics, vital signs on admission, Abbreviated Injury Scale for each body area, Injury Severity Score (ISS), and therapeutic modality were extracted. Mortality and hospital length of stay were stratified according to the severity of pancreatic injury and therapeutic modality. RESULTS: There were 388,137 patients with blunt abdominal trauma. Overall, 12,112 patients (3.1%) sustained pancreatic injury. Isolated pancreatic injury occurred in 2,528 (0.7%) of all abdominal injuries or 20.9% of pancreatic injuries. Most injuries were low-grade Organ Injury Scale ((OIS) score of 2, 82.7%) with only a small percentage of higher-grade injuries (OIS score of 3, 7.9%; OIS score of 4, 3.9%; and OIS score of 5, 5.5%). Overall, most patients (74.1%) were managed nonoperatively. Nonoperative management was selected in 80.5% of pancreas OIS score of 2, 48.5% of OIS score of 3, and 40.9% of OIS scores of 4 to 5. The overall mortality rate was 2.4%, while in severe pancreatic trauma it was 3.0%. In minor pancreatic trauma, nonoperative management was associated with lower mortality and shorter hospital length of stay than operative management. However, in the group of patients with severe pancreatic trauma (OIS scores, 4-5) nonoperative management was associated with higher mortality and longer hospital stay than definitive operative management of the pancreas. CONCLUSIONS: The mortality in isolated pancreatic trauma is low, even in severe injuries. Nonoperative management of minor pancreatic injuries is associated with lower mortality and shorter hospital stay than operative management. However, in severe trauma, nonoperative management is associated with higher mortality and longer hospital stay than operative management. LEVEL OF EVIDENCE: Prognostic study, level III; therapeutic study, level IV.

New developments in electroconvulsive therapy and magnetic seizure therapy.

New findings regarding the mechanisms of action of electro-convulsive therapy (ECT) have led to novel developments in treatment technique to further improve this highly effective treatment for major depression. These new approaches include novel placements, optimization of electrical stimulus parameters, and new methods for inducing more targeted seizures(eg, magnetic seizure therapy [MST]). MST is the use of transcranial magnetic stimulation to induce a seizure. Magnetic fields pass through tissue unimpeded, providing more control over the site and extent of stimulation than can be achieved with ECT. This enhanced control represents a means of focusing the treatment on target cortical structures thought to be essential to antidepressant response and reducing spread to medial temporal regions implicated in the cognitive side effects of ECT. MST is at an early stage of development. Preliminary results suggest that MST may have some advantages over ECT in terms of subjective side effects and acute cognitive functioning. Studies designed to address the antidepressant efficacy of MST are underway. As with all attempts to improve convulsive therapy technique, the clinical value of MST will need to be established through controlled clinical trials. This article reviews the experience to date with MST, and places this work in the broader context of other means of optimizing convulsive therapy in the treatment of depression.

Ehlers-danlos syndrome-hypermobility type and hemorrhoids.

Ehlers-Danlos syndrome-hypermobility type (EDS-HT) is a connective tissue disorder associated with chronic musculoskeletal pain. The diagnosis is based on simple clinical examination, although it is easily overlooked. Herein we present a case of EDS-HT associated with hemorrhoids and suggest that there may be an association between the two conditions.

A severe case of Angiostrongylus eosinophilic meningitis with encephalitis and neurologic sequelae in Hawa'i.

Angiostrongylus eosinophilic meningitis is caused by infection with larvae of the rat lungworm, Angiostrongylus cantonensis. We report the case of an adult who ingested a raw, giant African snail (Achatina fulica) on the island of O'ahu in Hawa'i and developed an eosinophilic meningoencephalitis with severe headache, confusion, sixth cranial nerve palsy, ataxia, limb weakness, and paresthesia. He was treated with lumbar punctures to relieve pressure, high dose corticosteroids, and 14 days of albendazole. He had a prolonged convalescence, requiring 3 months of prednisone, and still had evidence of motor nerve weakness 4 months after exposure. A field investigation at the site of exposure yielded 5 of 9 Achatina fulica snails with evidence of A. cantonensis DNA by PCR. Cerebrospinal fluid samples from the patient were negative acutely but positive on day 15 of symptoms, using an investigational, real-time PCR assay. We discuss clinical management of this case in light of the current medical literature.

Vanadate but not tungstate prevents the fructose-induced increase in GLUT5 expression and fructose uptake by neonatal rat intestine.

Intermediary signals, precociously enhancing GLUT5 transcription in response to perfusion of its substrate, fructose, in the small intestine of neonatal rats, are not known. Because glucose-6-phosphatase (G6Pase), glucose-6-phosphate translocase (G6PT), and fructose-1,6-bisphosphatase (FBPase) expression increases parallel to or precedes that of GLUT5, we investigated the link between these gluconeogenic genes and GLUT5 by using vanadate or tungstate, potent inhibitors of gluconeogenesis. Small intestinal perfusions of 20-d-old rats were performed with fructose alone, fructose + vanadate or tungstate, glucose alone, and glucose + vanadate or tungstate. As expected, fructose, but not glucose nor glucose + inhibitor perfusion, increased GLUT5 mRNA abundance and fructose transport. Fructose perfusion dramatically increased G6Pase mRNA abundance but had no effect on G6Pase activity. In sharp contrast, fructose perfusion did not increase FBPase gene expression but stimulated FBPase activity. Both vanadate and tungstate significantly inhibited G6Pase activity but did not prevent the fructose-induced increases in G6Pase and G6PT gene expression. Perfusion with fructose + vanadate prevented the fructose-induced increases in fructose transport and GLUT5 mRNA abundance, whereas perfusion with fructose + tungstate did not. Interestingly, vanadate, but not tungstate, inhibited the fructose-induced increase in FBPase activity. Thus, vanadate inhibition of fructose-induced increases in FBPase activity paralleled exactly vanadate inhibition of fructose-induced increases in GLUT5 mRNA abundance and activity. Fructose-induced changes in FBPase activity may regulate changes in GLUT5 expression and activity in the small intestine of neonatal rats. The marked increases in intestinal G6Pase and GLUT5 mRNA abundance may be a parallel response to different factors released during fructose perfusion.

Binding to Elongin C inhibits degradation of interacting proteins in yeast.

Elongin C is a highly conserved, low molecular weight protein found in a variety of multiprotein complexes in human, rat, fly, worm, and yeast cells. Among the best characterized of these complexes is a mammalian E3 ligase that targets proteins for ubiquitination and subsequent degradation by the 26 S proteasome. Despite its crucial role as a component of such E3 ligases and other complexes, the specific function of Elongin C is unknown. In yeast, Elongin C is a non-essential gene and there is no obvious phenotype as associated with its absence. We previously reported that in Saccharomyces cerevisiae Elongin C (Elc1) interacts specifically and strongly with a class of proteins loosely defined as stress response proteins. In the present study, we examined the role of yeast Elc1 in the turnover of two of these binding partners, Snf4 and Pcl6. Deletion of Elc1 resulted in decreased steady-state levels of Snf4 and Pcl6 as indicated by Western blot analysis. Northern blot analysis of mRNA prepared from elc1 null and wild type strains revealed no difference in mRNA levels for Snf4 and Pcl6 establishing that the effects of Elc1 are not transcriptionally mediated. Reintroduction of either yeast or human Elongin C into Elc1 null strains abrogated this effect. Taken together, these data document that the levels of Snf4 and Pcl6 are dependent on the presence of Elc1 and that binding to Elc1 inhibits the degradation of these proteins. The results suggest a new function for yeast Elongin C that is distinct from a direct role in targeting proteins for ubiquitination and subsequent proteolysis.