Fat Distribution in Schizophrenia Patients: A Pilot Study Comparing First- and Second-Generation Antipsychotics.

BACKGROUND: Introduction of second-generation antipsychotics (SGAs) has reduced neurologic toxicity but are associated with increased weight gain and obesity. The objective of this pilot study is to compare the effects of first-generation antipsychotics (FGAs) and SGAs in patients with schizophrenia on body fat and presumed concomitant metabolic parameters. METHODS: Study compared schizophrenia nondiabetic men treated with FGAs (group 1, n = 5) and men treated with SGAs (group 2, n = 9). Each subject completed psychiatric and endocrine evaluation including severity of psychiatric symptoms, adverse effects, body weight, body composition, and measurements of glucose, insulin, adipokines, and inflammatory markers. Student t test was used for statistical analysis. RESULTS: Men treated with FGAs had a lower mean body mass index with a trend toward statistical significance (25.3 ± 1.4 vs 29.3 ± 1.7, P = 0.06). Treatment with FGAs was associated with lower waist/height ratio (0.55 ± 0.02 vs 0.62 ± 0.02, P = 0.036) and android fat mass index (0.62 ± 0.01 vs 0.96 ± 0.1, P = 0.03). Homeostasis Model Assessment for insulin resistance values were suggestive of significantly lower peripheral insulin resistance in men treated with FGAs (0.92 ± 0.15 vs 2.3 ± 0.34, P = 0.014). CONCLUSIONS: The results of this study are significant for decreased peripheral insulin resistance in men treated with SGAs in a setting of no significant age difference and only a trend toward higher body mass index, but consistent documentation of increased abdominal fat by 3 different methodologies. Future studies involving larger number of subjects are warranted to verify the present findings.

Longitudinal Progression of Patients with Long COVID Treated in a Post-COVID Clinic: A Cross-Sectional Survey.

BACKGROUND: In addition to the morbidity and mortality associated with acute infection, COVID-19 has been associated with persistent symptoms (>30 days), often referred to as Long COVID (LC). LC symptoms often cluster into phenotypes, resembling conditions such as fibromyalgia, postural orthostatic tachycardiac syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). LC clinics have been established to best address the needs of LC patients and continuity of care. We developed a cross-sectional survey to assess treatment response through our LC Clinic (LCC). METHODS: A 25-question survey (1-10 Likert scale) was expert- and content-validated by LCC clinicians, patients, and patient advocates. The survey assessed LC symptoms and the helpfulness of different interventions, including medications and supplements. A total of 852 LCC patients were asked to complete the survey, with 536 (62.9%) responding. RESULTS: The mean time from associated COVID-19 infection to survey completion was 23.2 ± 6.4 months. The mean age of responders was 52.3 ± 14.1 (63% females). Self-reported symptoms were all significantly improved (P < .001) from the initial visit to the LCC (baseline) to the time of the follow-up survey. However, only 4.5% (24/536) of patients rated all symptoms low (1-2) at the time of the survey, indicating low levels of full recovery in our cohort. The patients rated numerous interventions as being helpful, including low-dose naltrexone (45/77; 58%), vagal nerve stimulation (18/34; 53%), and fisetin (28/44; 64%). CONCLUSIONS: Patients report general improvements in symptoms following the initial LCC visit, but complete recovery rates remain low at 23.2 ± 6.4 months.

Postdischarge Video Visits for Adherence to Hospital Discharge Recommendations: A Randomized Clinical Trial.

Objective: To determine whether a postdischarge video visit with patients, conducted by hospital medicine advanced practice providers, improves adherence to hospital discharge recommendations. Patients and Methods: We conducted a single-institution 2-site randomized clinical trial with 1:1 assignment to intervention vs control, with enrollment from August 10, 2020, to June 23, 2022. Hospital medicine patients discharged home or to an assisted living facility were randomized to a video visit 2-5 days postdischarge in addition to usual care (intervention) vs usual care (control). During the video visit, advanced practice providers reviewed discharge recommendations. Both intervention and control groups received telephone follow-up 3-6 days postdischarge to ascertain the primary outcome of adherence to all discharge recommendations for new and chronic medication management, self-management and action plan, and home support. Results: Among 1190 participants (594 intervention; 596 control), the primary outcome was ascertained in 768 participants (314 intervention; 454 control). In intervention vs control, there was no difference in the proportion of participants with the primary outcome (76.7% vs 72.5%; P=.19) or in the individual domains of the primary outcome: new and chronic medication management (94.1% vs 92.8%; P=.50), self-management and action plan (76.5% vs 71.5%; P=.18), and home support (94.1% vs 94.3%; P=.94). Women receiving intervention vs control had higher adherence to recommendations (odds ratio, 1.77; 95% CI, 1.08-2.91). Conclusion: In hospital medicine patients, a postdischarge video visit did not improve adherence to discharge recommendations. Potential gender differences in adherence require further investigation.Clinicaltrials.gov number, NCT04547803.

Glucose ingestion acutely lowers pulsatile LH and basal testosterone secretion in men.

Chronic hyperglycemia inhibits the male gonadal axis. The present analyses test the hypothesis that acute glucose ingestion also suppresses LH and testosterone (T) secretion and blunts the LH-T dose-response function. The design comprised a prospectively randomized crossover comparison of LH and T secretion after glucose vs. water ingestion in a Clinical Translational Research Center. The participants were healthy men (n = 57) aged 19-78 yr with body mass index (BMI) of 20-39 kg/m(2). The main outcome measurements were deconvolution and LH-T dose-response analyses of 10-min data. LH-T responses were regressed on glucose, insulin, leptin, adiponectin, age, BMI, and CT-estimated abdominal visceral fat. During the first 120 min after glucose ingestion, for each unit decrease in LH concentrations, T concentrations decreased by 86 (27-144) ng/dl (r = 0.853, P < 0.001). Based upon deconvolution analysis, glucose compared with water ingestion reduced 1) basal (nonpulsatile; P < 0.001) and total (P < 0.001) T secretion without affecting pulsatile T output and 2) pulsatile (P = 0.043) but not basal LH secretion. By multivariate analysis, pulsatile LH secretion positively predicted basal T secretion after glucose ingestion (r = 0.374, P = 0.0042). In addition, the glucose-induced fall in pulsatile LH secretion was exacerbated by higher fasting insulin concentrations (P = 0.054) and attenuated by higher adiponectin levels (P = 0.0037). There were no detectable changes in the analytically estimated LH-T dose-response curves (P > 0.30). In conclusion, glucose ingestion suppresses pulsatile LH and basal T secretion acutely in healthy men. Suppression is influenced by age, glucose, adiponectin, and insulin concentrations.

Dismissal disagreement and discharge delays: Associations of patient-clinician plan of care agreement with discharge outcomes.

BACKGROUND: Many hospitalized patients do not understand or agree with their clinicians about their discharge plan. However, the effect of disagreement on discharge outcomes is unknown. OBJECTIVE: To measure the correlation between patient-clinician care agreement and discharge outcomes. DESIGN: A prospective cohort study was performed from September 2019 to March 2020 (Rochester, MN, USA). SETTING AND PARTICIPANTS: Internal medicine patients and their primary clinician (resident, advanced practice clinician or attending) hospitalized from September 2019-March 2020 at Mayo Clinic Hospital. Participants were independently surveyed following hospital day #3 ward rounds regarding the goals of the hospitalization and discharge planning. MAIN OUTCOME AND MEASURES: Patient-clinician agreement for main diagnosis, patient's main concern, and four domains of discharge planning was assessed. Readiness for hospital discharge, delayed discharge, and 30-day readmission was measured. Then, associations between patient-clinician agreement, delayed discharge, and 30-day readmissions were analyzed using multivariable logistic regression. RESULTS: Of the 436 patients and clinicians, 17.7% completely agreed about what needs to be accomplished before dismissal, 40.8% agreed regarding discharge date, and 71.1% agreed regarding discharge location. In the multivariable model, patient-clinician agreement scores were not significantly correlated with discharge outcomes. Patient-clinician agreement on discharge location was higher for those discharged to home (81.5%) versus skilled nursing facility (48.5%) or assisted living (42.9%) (p < .0001). The agreement on the expected length of stay was highest for home-goers (45.9%) compared to skilled nursing (32.0%) or assisted living (21.4%) (p = .004). CONCLUSIONS: Patients and their clinicians frequently disagree about when and where a patient will go after hospitalization, particularly for those discharged to a skilled nursing facility. While disagreement did not predict discharge outcomes, our findings suggest opportunities to improve effective communication and promote shared mental models regarding discharge earlier in the hospital stay.

Relationships Between Time-at-Bedside During Hospital Ward Rounds, Clinician-Patient Agreement, and Patient Experience.

Hospital medicine ward rounds are often conducted away from patients' bedsides, but it is unknown if more time-at-bedside is associated with improved patient outcomes. Our objective is to measure the association between "time-at-bedside," patient experience, and patient-clinician care agreement during ward rounds. Research assistants directly observed medicine services to quantify the amount of time spent discussing each patient's care inside versus outside the patient's room. "Time-at-bedside" was defined as the proportion of time spent discussing a patient's care in his or her room. Patient experience and patient-clinician care agreement both were measured immediately after ward rounds. Results demonstrated that the majority of patient and physicians completely agreement on planned tests (66.3%), planned procedures (79.7%), medication changes (50.6%), and discharge location (66.9%), but had no agreement on the patient's main concern (74.4%) and discharge date (50.6%). Time-at-bedside was not correlated with care agreement or patient experience (P > .05 for all comparisons). This study demonstrates that spending more time at the bedside during ward rounds, alone, is insufficient to improve patient experience.

Music Therapy for Anxiety and Pain After Spinal Cord Injury: A Pilot Study.

BACKGROUND: Music therapy (MT) programs have been used in various health care settings to reduce patients' pain, anxiety, and stress. However, few studies have investigated its effects on patients with spinal cord injury (SCI), a frequently serious event requiring extensive rehabilitation. OBJECTIVE: This pilot study evaluated the feasibility of offering music-assisted relaxation (MAR) during rehabilitation for patients with SCI. We also measured the effect of MAR on the patients' pain, anxiety, and stress levels. METHODS: Patients were hospitalized at Mayo Clinic (Rochester, Minnesota) from September 2015 through September 2017 for rehabilitation of an SCI. Eligible patients received 2, 20-minute, personalized MAR sessions. Interventions were facilitated by a board-certified music therapist (MT-BC) and included diaphragmatic breathing, guided imagery, and passive muscle relaxation with live guitar accompaniment and spoken, improvised, or singing voice. Two surveys (Generalized Anxiety Disorder [GAD-7] and Perceived Stress Scale [PSS-10]) were used at the time of study consent and again upon hospital dismissal. Pain, anxiety, and relaxation were assessed before and after both MT sessions with visual analog scales (VASs), scored from 0 to 10. Participants completed a 7-question satisfaction survey after the second MAR session. RESULTS: Twenty patients were enrolled (12 men, 8 women); 13 (65%) completed the MAR interventions. The mean (SD) age was 53.7 (17.7) years. VAS scores for pain significantly improved after both sessions (P ≤ .02). VAS scores for anxiety also significantly improved after both sessions (P ≤ .02), as did VAS scores for relaxation (P ≤ .02 for both). The satisfaction survey indicated that patients generally believed that they benefited from MT. Rehabilitation staff indicated that MT did not interfere with routine clinical care. CONCLUSION: MT with live MAR is a feasible treatment for patients with SCI and may be effective for reducing their pain and anxiety.

Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease.

BACKGROUND: Senescent cells, which can release factors that cause inflammation and dysfunction, the senescence-associated secretory phenotype (SASP), accumulate with ageing and at etiological sites in multiple chronic diseases. Senolytics, including the combination of Dasatinib and Quercetin (D + Q), selectively eliminate senescent cells by transiently disabling pro-survival networks that defend them against their own apoptotic environment. In the first clinical trial of senolytics, D + Q improved physical function in patients with idiopathic pulmonary fibrosis (IPF), a fatal senescence-associated disease, but to date, no peer-reviewed study has directly demonstrated that senolytics decrease senescent cells in humans. METHODS: In an open label Phase 1 pilot study, we administered 3 days of oral D 100 mg and Q 1000 mg to subjects with diabetic kidney disease (N = 9; 68·7 ±â€¯3·1 years old; 2 female; BMI:33·9 ±â€¯2·3 kg/m2; eGFR:27·0 ±â€¯2·1 mL/min/1·73m2). Adipose tissue, skin biopsies, and blood were collected before and 11 days after completing senolytic treatment. Senescent cell and macrophage/Langerhans cell markers and circulating SASP factors were assayed. FINDINGS: D + Q reduced adipose tissue senescent cell burden within 11 days, with decreases in p16INK4A-and p21CIP1-expressing cells, cells with senescence-associated ß-galactosidase activity, and adipocyte progenitors with limited replicative potential. Adipose tissue macrophages, which are attracted, anchored, and activated by senescent cells, and crown-like structures were decreased. Skin epidermal p16INK4A+ and p21CIP1+ cells were reduced, as were circulating SASP factors, including IL-1α, IL-6, and MMPs-9 and -12. INTERPRETATION: "Hit-and-run" treatment with senolytics, which in the case of D + Q have elimination half-lives <11 h, significantly decreases senescent cell burden in humans. FUND: NIH and Foundations. ClinicalTrials.gov Identifier: NCT02848131. Senescence, Frailty, and Mesenchymal Stem Cell Functionality in Chronic Kidney Disease: Effect of Senolytic Agents.

Cardiac Events after Noncardiac Surgery in Patients Undergoing Preoperative Dobutamine Stress Echocardiography: Findings From the Mayo Poce-DSE Investigators.

BACKGROUND: Current guidelines support the use of dobutamine stress echocardiography (DSE) prior to noncardiac surgery in higher-risk patients who are unable to perform at least 4 metabolic equivalents of physical activity. We evaluated postoperative outcomes of patients in different operative risk categories after preoperative DSE. METHODS: We collected data from the medical record on 4494 patients from January 1, 2006 to December 31, 2011 who had DSE up to 90 days prior to a noncardiac surgery. Patients were divided into low, intermediate, and high preoperative surgery-specific risk. Baseline demographic data and risk factors were abstracted from the medical record, as were postoperative cardiac events including myocardial infarction, cardiac arrest, and mortality within 30 days after surgery. RESULTS: There were 103 cardiac outcomes (2.3%), which included myocardial infarction (n = 57, 1.3%), resuscitated cardiac arrest (n = 26, 0.6%), and all-cause mortality (n = 40, 0.9%). Cardiac event rates were 0.0% (95% confidence interval [CI], 0.0%-3.9%) in the low-surgical-risk group, 2.1% (95% CI, 1.6%-2.5%) in the intermediate-surgical-risk group, and 3.4% (95% CI, 2.0%-4.4%) in the high-risk group. Thirty-day postoperative mortality rates were 0%, 0.9%, and 0.8% for the low-risk, intermediate-risk, and high-risk surgical groups, respectively, and were not statistically different. CONCLUSIONS: These findings demonstrate low cardiac event rates in patients who underwent a DSE prior to noncardiac surgery. The previously accepted construct of low-, intermediate-, and high-risk surgeries based on postoperative events of <1%, 1%-5%, and >5% overestimates the actual risk in contemporary settings.

Adiposity-independent hypoadiponectinemia as a potential marker of insulin resistance and inflammation in schizophrenia patients treated with second generation antipsychotics.

OBJECTIVE: The purpose of this study was to explore body fat independent effect of second generation antipsychotics (SGAs) on measures of glucose and adipokine homeostasis, and markers of inflammation. METHOD: Eight non-diabetic men with schizophrenia (age: 55±3years, BMI: 29.7±1.2kg/m(2)) on SGAs were studied after an overnight fast. DXA and single-cut CT of abdomen were respectively used for the assessment of total body and abdominal fat. Blood samples were collected for measurements of glucose, insulin, leptin, adiponectin, C-reactive protein (CRP), and TNF-α. Data in schizophrenic subjects were compared to eight age (55±2.8years) and BMI (29.6±1.1kg/m(2)) matched healthy men. RESULTS: The results were significant for markedly decreased serum adiponectin in schizophrenia patients (4.6±0.9 vs 11.1±1.5ng/mL, p=0.001). Lower levels of adiponectin in schizophrenia men were associated with significant increases in insulin resistance (4.2±0.7 vs 1.7±0.4, p=0.004), CRP (3.5±1.2 vs 1.2±0.3, p=0.037), and leptin (12±1.4 vs 8.5±1.4ng/mL, p=0.05). Various measures of adiposity, including fat mass index (FMI) and abdominal fat were not different in the two study groups. CONCLUSIONS: These findings in the context of comparable age and total body/abdominal fat mass are assumed to be either disease specific, and/or treatment inflicted. The definitive invoking etiology and a presumptive role of hypoadiponectinemia in the development of insulin resistance and increased risk of inflammation warrant future investigation.