The effect of zolpidem-CR on the suicide item of the Hamilton Rating Scale for Depression in outpatients with depression, insomnia and suicidal ideation: Lessons learned.

The REST-IT study found the addition of zolpidem-controlled release (CR) provided a significant reduction in observer-rated measurement of suicidal ideation (the Columbia Suicide Severity Rating Scale) in 103 depressed outpatients with insomnia and suicidal ideation, but without significant change in a self-report measure of suicidal ideation (the Scale for Suicide Ideation). This secondary analysis of the REST-IT data examined the suicide item of another observer-rated scale, the Hamilton Rating Scale for Depression (HRSD), further clarifying the impact of insomnia-focused treatment on suicidal ideation. This analysis established a significant advantage for zolpidem-CR compared with placebo on the HRSD suicide item.

Daytime autonomic nervous system functions differ among adults with and without insomnia symptoms.

STUDY OBJECTIVES: We gathered data to determine whether daytime assays of the autonomic nervous system would differ between persons with no vs modest insomnia symptoms and would correlate with the severity of insomnia symptoms in patients. METHODS: This report is composed of 2 studies. Study 1 conducted pupillary light reflex (PLR) measurements in community volunteers who were not seeking medical care. Study 2 contrasted PLR and heart rate variability in a different sample of community volunteers and a comparison sample of adults seeking outpatient care for insomnia and psychiatric problems. All measurements were taken between 3 and 5 pm. RESULTS: In Study 1, volunteers with modest insomnia symptom severity had a more rapid PLR average constriction velocity compared with those with no symptoms. In Study 2, lower heart rate variability, indicating higher levels of physiologic arousal, generally were in agreement with faster PLR average constriction velocity, both of which indicate higher levels of arousal. Insomnia symptom severity was highly correlated with faster average constriction velocity in the patient sample. CONCLUSIONS: These studies suggest that (1) daytime measurements of the autonomic nervous system differ between persons with modest vs no insomnia symptoms and (2) insomnia symptom severity is highly correlated with PLR. Daytime measurement of autonomic nervous system activity might allow for daytime point-of-care measurement to characterize the level of physiologic arousal to define a hyperarousal subtype of insomnia disorder. CITATION: McCall WV, Looney SW, Zulfiqar M, et al. Daytime autonomic nervous system functions differ among adults with and without insomnia symptoms. J Clin Sleep Med. 2023;19(11):1885-1893.

Reduction of SARS-CoV-2 salivary viral load with pre-procedural mouth rinses: a randomised, controlled, clinical trial.

Introduction The purpose of this study was to test the short-term efficacy of four commercial mouthwashes versus water in reducing SARS-CoV-2 viral load in the oral cavity over clinically relevant time points.Methods In total, 32 subjects that were proven SARS-CoV-2-positive via polymerase chain reaction (PCR)-based diagnostic test were recruited and randomised into five parallel arms. Cycle threshold (Ct) values were compared in saliva samples between the groups, as well as within the groups at baseline (pre-rinse), zero hours, one hour and two hours post-rinse, using SARS-CoV-2 reverse transcription-PCR analysis.Results We observed a significant increase in Ct values in saliva samples collected immediately after rinsing with all the four mouthwashes - 0.12% chlorhexidine gluconate, 1.5% hydrogen peroxide, 1% povidone iodine, or Listerine - compared to water. A sustained increase in Ct values for up to two hours was only observed in the Listerine and chlorohexidine gluconate groups. We were not able to sufficiently power this clinical trial, so the results remain notional but encouraging and supportive of findings in other emerging mouthwash studies on COVID-19, warranting additional investigations.Conclusions Our evidence suggests that in a clinical setting, prophylactic rinses with Listerine or chlorhexidine gluconate can potentially reduce SARS-CoV-2 viral load in the oral cavity for up to two hours. While limited in statistical power due to the difficulty in obtaining this data, we advocate for pre-procedural mouthwashing, like handwashing, as an economical and safe additional precaution to help mitigate the transmission of SARS-CoV-2 from a potentially infected patient to providers.

Relationships among insomnia, executive function, and suicidal ideation in depressed outpatients: A mediation analysis.

Insomnia is a risk factor for suicide, and both are associated with cognitive problems. However, prior research has not examined insomnia, cognition, and suicidal ideation within one sample. We describe cross-sectional associations among insomnia, psychomotor speed, set shifting, and suicidal ideation in 85 depressed adults. Greater insomnia was associated with slower psychomotor speed, while slower psychomotor speed was associated with a greater level (i.e., elaboration of suicide planning) and intensity of suicidal ideation in the past week. Slower set shifting was associated with a greater level and intensity of suicidal ideation in the past week. Mediation analysis indicated that psychomotor speed and set shifting both had a significant total effect on the intensity of suicidal ideation in the past week; set shifting also had a significant total effect on the sum of intensity and suicidal ideation level in the past week. The level of insomnia explained only small percentages of the total effect of either psychomotor speed or set shifting on the intensity of suicidal ideation and the sum of intensity and suicidal ideation level. The findings in this sample demonstrate significant associations of slower psychomotor speed and set shifting with suicidal ideation, with negligible contribution from insomnia.

Hyperhomocysteinemia dysregulates plasma levels of polyunsaturated fatty acids-derived eicosanoids.

Hyperhomocysteinemia (HHcy) contributes to the incidence of many cardiovascular diseases (CVD). Our group have previously established crucial roles of eicosanoids and homocysteine in the incidence of vascular injury in diabetic retinopathy and renal injury. Using cystathionine-ß-synthase heterozygous mice (cßs+/-) as a model of HHcy, the current study was designed to determine the impact of homocysteine on circulating levels of lipid mediators derived from polyunsaturated fatty acids (PUFA). Plasma samples were isolated from wild-type (WT) and cßs+/- mice for the assessment of eicosanoids levels using LC/MS. Plasma 12/15-lipoxygenase (12/15-LOX) activity significantly decreased in cßs+/- vs. WT control mice. LOX-derived metabolites from both omega-3 and omega-6 PUFA were also reduced in cßs+/- mice compared to WT control (P < 0.05). Contrary to LOX metabolites, cytochrome P450 (CYP) metabolites from omega-3 and omega-6 PUFA were significantly elevated in cßs+/- mice compared to WT control. Epoxyeicosatrienoic acids (EETs) are epoxides derived from arachidonic acid (AA) metabolism by CYP with anti-inflammatory properties and are known to limit vascular injury, however their physiological role is limited by their rapid degradation by soluble epoxide hydrolase (sEH) to their corresponding diols (DiHETrEs). In cßs+/- mice, a significant decrease in the plasma EETs bioavailability was obvious as evident by the decrease in EETs/ DiHETrEs ratio relative to WT control mice. Cyclooxygenase (COX) metabolites were also significantly decreased in cßs+/- vs. WT control mice. These data suggest that HHcy impacts eicosanoids metabolism through decreasing LOX and COX metabolic activities while increasing CYP metabolic activity. The increase in AA metabolism by CYP was also associated with increase in sEH activity and decrease in EETs bioavailability. Dysregulation of eicosanoids metabolism could be a contributing factor to the incidence and progression of HHcy-induced CVD.

Repetitive Transcranial Magnetic Stimulation Promotes Rapid Psychiatric Stabilization in Acutely Suicidal Military Service Members.

OBJECTIVE: This study presents data for using accelerated transcranial magnetic stimulation (TMS) as an intervention for suicidal crisis (SC). METHODS: This prospective, single-site, randomized, double-blind trial enrolled active-duty military participants with SC to receive either active TMS (n = 59) or sham TMS (n = 61) 3 times per day for 3 consecutive days. Our primary outcome, the Beck Scale for Suicidal Ideation-current (SSI-C), was measured before each session of TMS. Secondary outcomes measured both the SSI-C and the Beck Scale for Suicidal Ideation-total daily for the 3 intervention days and at 1, 3, and 6 months of follow-up. RESULTS: In the modified intention to treat (mITT) analysis of SSI-C changes over treatment sessions, the TMS active group had accelerated decline in suicidal ideation as compared with sham: ß for interaction was 0.12 points greater SSI-C decline per session (standard error [SE], 0.06) in TMS versus sham (P = 0.04). In both the mITT and per-protocol active TMS groups, the mean final SSI-C scores were below 3. These scores remained below 3 for the entire 6-month follow-up period. CONCLUSIONS: In this military trial of suicidal patients, we found that both active and sham accelerated TMS rapidly reduces SC. Moreover, in the mITT analysis, there was a statistically significant antisuicidal benefit of active TMS versus sham TMS in the primary outcome. Both the mITT and per-protocol groups moved from higher to approximately 7 times lower suicide risk strata and remained there for the duration of the study. Further studies are warranted to understand accelerated TMS' full potential as a treatment for SC.

Promoting Community Awareness of Lung Cancer Screening Among Disparate Populations: Results of the cancer-Community Awareness Access Research and Education Project.

BACKGROUND: Lung cancer is the no. 1 cause of cancer death in the United States. Racial/ethnic minority and medically underserved populations suffer higher mortality than whites. Early detection through uptake of low-dose computed tomography (LDCT) among screening-eligible adults may mitigate high mortality. However, nearly 5 years since the publication of the US Preventive Services Task Force lung cancer screening guideline, population awareness of LDCT is low, and only 4% of screening-eligible adults have undergone screening. OBJECTIVE: This project used an education intervention to change participants' knowledge, attitudes, and beliefs about cancer risk factors and lung cancer and to connect eligible individuals to LDCT screening and tobacco cessation services. INTERVENTIONS/METHODS: Community-engaged strategies were used to deliver a 4-week educational program in 13 community sites. Trained community health workers delivered the intervention. The intervention was guided by the Health Belief Model. Data were collected by survey to 481 participants; 93% were African American, the majority was female (73.1%), mean age was 58.3 (SD, 10.9) years. RESULTS: There were knowledge increase regarding lung cancer screening (P = .001), a significant decrease in Perceived Severity and Perceived Barriers subscales (P = .001), and an overall increase in response to Perceived Benefits of lung cancer screening and Self-efficacy (P = .001). Fifty-four percent of tobacco users engaged in cessation; 38% of screening-eligible participants underwent LDCT screening. CONCLUSIONS: Community health workers are effective in increasing awareness of lung cancer screening and affecting behavior change among disparate populations. IMPLICATIONS FOR PRACTICE: Community health workers may have a clinical role in LDCT shared decision making.

Meta-analysis of randomized controlled trials of galantamine in schizophrenia: significant cognitive enhancement.

Cognitive impairments are core features of schizophrenia and the best predictor of functional outcome. Cholinergic system and alpha-7 nicotinic acetylcholine (α7nACh) receptors are strongly implicated in the pathophysiologic mechanisms associated with cognitive impairments in schizophrenia. Galantamine is not only a reversible, competitive inhibitor of acetylcholinesterase but also a type I positive allosteric modulator of α7nACh receptors. The objective of this meta-analysis was to examine the efficacy of galantamine for cognitive symptoms of schizophrenia. In the meta-analysis that included six randomized controlled trials (RCTs, N=226), cognitive impairments significantly improved with galantamine compared to placebo, with a small Hedges' g effect size of 0.233. This finding is consistent with other RCTs in schizophrenia with medications with a similar mechanism of action. On the basis of the results from all the failed (although some efficacy has been shown) RCTs to date in schizophrenia, targeting only one pathophysiologic mechanism may be insufficient to detect a clinically meaningful signal. Nicotinergic medications, like any other add-on medications, are unlikely to be effective as stand-alone medications. Hence, these medications may have to be combined with other medications with complementary mechanisms such as glutamatergic/N-methyl-D-aspartate systems to detect a meaningful effect size for the three domains of psychopathology.

Does a Difference Exists in Comprehensive Basic Science Examination Scores of 4-Year versus 6-Year Oral-Maxillofacial Surgery Residents?

PURPOSE: The Comprehensive Basic Science Examination (CBSE) scores have significant effects on the applications of oral-maxillofacial surgery (OMS) residency candidates. However, a comparison of the scores of residents that match to 4-year versus 6-year programs is lacking. The present study compared the CBSE scores of OMS residency candidates who had matched to 4-year and 6-year tracks in the 2018-2019 application cycle. MATERIALS AND METHODS: In the present cross-sectional analysis, an anonymous questionnaire was sent electronically to program directors of all OMS residency programs in the United States using the online survey engine Survey Monkey. Data were collected on the CBSE scores of their postgraduate year 1 categorical residents and whether the resident was on a 4-year or 6-year track. The CBSE scores were summarized overall and by the type of residency program (4 vs 6 year) using the mean, standard deviation, median, mode, minimum, and maximum. In addition, the 2-sample t test was used to compare the mean CBSE score between the 4-year programs (4YPs) and 6-year programs (6YPs). RESULTS: A total of 37 scores were received from the 4YPs and 31 from the 6YPs. The overall mean CBSE score was 68.9. Using the 2-sample t test, the mean CBSE score differed significantly between the 4YPs and 6YPs (t = -6.59; df = 66; P < .0001). CONCLUSIONS: Candidates matching into 6-year positions showed significantly higher mean scores on the CBSE examination compared with those matching into 4-year positions.

Accelerated Biologic Aging, Chronic Stress, and Risk for Sepsis and Organ Failure Following Trauma.

Chronic stress and accelerated aging have been shown to impact the inflammatory response and related outcomes like sepsis and organ failure, but data are lacking in the trauma literature. The purpose of this study was to investigate potential relationships between pretrauma stress and posttrauma outcomes. The hypothesis was that pretrauma chronic stress accelerates aging, which increases susceptibility to posttrauma sepsis and organ failure. In this prospective, correlational study, chronic stress and accelerated biologic aging were compared to the occurrence of systemic inflammatory response syndrome, sepsis, and organ failure in trauma patients aged 18-44 years. Results supported the hypothesis with significant overall associations between susceptibility to sepsis and accelerated biologic aging (n = 142). There were also significant negative associations between mean cytokine levels and chronic stress. The strongest association was found between mean interleukin-1ß (IL-1ß) and human telomerase reverse transcriptase (hTERT), r(101) = -0.28), p = .004. Significant negative associations were found between mean cytokine levels, IL-12p70, r(108) = -0.20, p = .034; and tumor necrosis factor-α (TNF-α), r(108) = -0.20, p = .033, and positive life events via the behavioral measure of chronic stress. Results may help identify individuals at increased risk for poor outcomes of trauma and inform interventions that may reduce the risk for sepsis and organ failure.

Student Race and Gender and Patient Encounters in a Family Medicine Clerkship.

BACKGROUND AND OBJECTIVES: The purpose of this study was to determine the association of students' race and gender with the race, gender, age, patient numbers, and problems encountered during a third-year family medicine clerkship across a geographically distributed clinical teaching network. METHODS: Student patient experience logbook data from two separate but adjacent 3-year periods were analyzed. Mixed-effects regression models and generalized linear mixed models were used to determine the relationship between student race and gender on number and demographics of patients encountered and odds of encountering required conditions and gender-specific conditions at least once during the clerkship. RESULTS: A total of 458 students documented 66,752 encounters during academic years 2008 through 2010, and 498 students documented 70,213 encounters during academic years 2011 through 2013. The first cohort averaged 145.8 (SD 24.0) encounters per student and the second cohort averaged 141.1 (SD 19.5) encounters per student. Females had more encounters during the first period, but no difference in the second. There was no difference in average encounters between white and nonwhite students during the first period, but during the second, nonwhite students had more encounters. A few differences were found in odds of encountering required conditions or gender-specific conditions, but none were consistent across time. CONCLUSIONS: Family medicine clerkship students in this geographically distributed network did not experience significant differences in patient demographics, conditions, or gender-specific diseases, based on their gender or race. The teaching sites in the study were monitored continuously to ensure consistent clinical experiences in volume and scope.

Design of a Community-Based Lung Cancer Education, Prevention, and Screening Program.

Uptake of low-dose computed tomography (LDCT) for lung cancer screening is extremely low. Efforts to promote screening are warranted, especially among disparate groups such as racial/ethnic minorities and those of lower socioeconomic status. This article describes the design and implementation strategies of the ongoing cancer-Community Awareness Access Research and Education (c-CARE) program. The purpose of c-CARE is to increase community awareness of lung cancer screening through education. Community health workers were trained to implement the intervention in 12 community sites. The Health Belief Model guided the evaluation and intervention development methods. Aims include changing participants' knowledge, attitude, and beliefs related to lung cancer and increasing lung cancer early detection and prevention behaviors by identifying and connecting high-risk and/or nicotine-dependent individuals to LDCT screening and/or tobacco cessation services. If effective, these methods could model increased dissemination to other high-risk communities.

Demographic, psychosocial, and behavioral associations with cancer screening among a homeless population.

BACKGROUND: Although cancer incidence and mortality is declining, cancer remains among the leading causes of death in the United States. Research shows that cancer morbidity and mortality can be reduced by early detection. Yet, both cancer risks and screening behavior remain understudied in the homeless population. METHODS: Researchers conducted a cross-sectional survey of homeless individuals (n = 201). The analysis describes the demographic, psychosocial, and behavioral associations with cancer screenings and knowledge of the lung cancer screening recommendation. RESULTS: Participants' mean age was 51.7 years (SD 13.6); the group was largely African American (77.3%) and male (67.9%). Among women, the breast and cervical cancer screening rates were 46.5% and 85.1%. Among men the prostate cancer screening rate was 34.2%. Among all participants, the colon cancer screening rate was 44%. Cancer risk behaviors were high. Lung cancer screening knowledge was low (23.0%). Some cancer screening behaviors were associated with age, income, health status, obesity, tobacco use, and physical activity. DISCUSSION: Despite higher cancer risk behaviors, knowledge and general participation rates for cancer screenings were below national benchmarks. CONCLUSION: To improve cancer survival among disparate populations, sustained community outreach is necessary to increase awareness of screening recommendations, identify high-risk individuals, and navigate them to resources.

Reexamining Metoclopramide's Role in the Prevention of Postoperative Nausea and Vomiting: A Secondary Analysis.

Postoperative nausea and vomiting (PONV) continue to be among the most undesirable and distressing complications following general anesthesia, affecting 20% to 30% of all surgical patients and up to 70% of patients with multiple known risk factors. The purpose of this study was to reexamine the effectiveness of metoclopramide in the prevention of PONV when stratified by PONV risk scores. Secondary data from 2,116 adult ambulatory surgical patients were analyzed. Participants were, on average (SD), 49.7 (15.4) years of age, with a mean body mass index of 28.3 (6.9) kg/m², and were primarily female (65%). Risk scores for PONV ranged from 0 to 4, with a mean of 2.6 (1.0). Metoclopramide, 10 mg intravenously (IV) alone; metoclopramide, 10 mg IV, combined with ondansetron, 4 mg IV; and metoclopramide, 10 mg IV, combined with dexamethasone, 8 mg IV, and ondansetron, 4 mg IV, had a beneficial effect for adult ambulatory surgical patients with PONV risk scores of 1 to 4. Although this cohort study had limitations, future studies should investigate metoclopramide based on risk score recommendations, and guidelines should be reevaluated.

Predicting relapse in schizophrenia: Is BDNF a plausible biological marker?

Understanding the biological processes that underlie why patients relapse is an issue of fundamental importance to the detection and prevention of relapse in schizophrenia. Brain Derived Neurotrophic Factor (BDNF), a facilitator of brain plasticity, is reduced in patients with schizophrenia. In the present study, we examined whether decreases in plasma BDNF levels could be used as a biological predictor of relapse in schizophrenia. A total of 221 patients were prospectively evaluated for relapse over 30months in the Preventing Relapse in Schizophrenia: Oral Antipsychotics Compared to Injectables: eValuating Efficacy (PROACTIVE) study. Serial blood samples were collected at a maximum of 23 time points during the 30-month trial and BDNF levels were measured in plasma samples by ELISA. Receiver Operating Characteristic (ROC) curve analysis indicated that BDNF was not a significant predictor of relapse, hospitalization or exacerbation. Regardless of treatment group (oral second generation antipsychotic vs. long-acting injectable risperidone microspheres), baseline BDNF value did not differ significantly between those who experienced any of the adverse outcomes and those who did not. While contrary to the study hypothesis, these robust results offer little support for the use of plasma BDNF alone as a biomarker to predict relapse in schizophrenia.

Lip repositioning for the treatment of excess gingival display: A systematic review.

BACKGROUND: Lip repositioning is a conservative surgical technique used to treat excess gingival display. An array of modifications has been introduced to the technique over time and as studies show the technique and its modifications to be successful, there is little standardized information for clinicians to make informed decisions when choosing this technique for the treatment of patients with excessive gingival display (EGD). OBJECTIVES: To review the current literature on the topic of lip repositioning for the treatment of excessive EGD, exploring outcome, and result longevity. METHODS: A structured systematic search was carried out using the Ovid database and Web of Science to identify published studies on lip repositioning technique. Search was restricted to studies in the English language, describing a surgical intervention. Case reports were included as the number of published studies was limited. RESULTS: The electronic search identified 93 articles, hand search identified 1 article, and reference search identified 1 article. After excluding duplicates and screening articles, a total of 22 articles met the inclusion criteria. An estimated mean improvement of 3.4 mm (95% confidence interval, 3.0-3.8 mm) was found possible with lip repositioning. Data analysis was performed using only 4 studies, amounting to a total of 33 patients. Potential risk of bias was identified in some of the studies included. CONCLUSIONS: Despite the limited available studies on lip repositioning, an estimated mean improvement of 3.4 mm was found to be possible with surgical lip repositioning, suggesting that the technique could be used successfully to treat EGD. However, more studies are necessary to properly evaluate the treatment approach and stability of the technique. CLINICAL SIGNIFICANCE: Recently, the demand for esthetics has significantly increased, driven by increased patient awareness and the search for an ideal smile. Creating the perfect smile is an intricate process that requires a multidisciplinary approach, with careful consideration of the lips and the gingival outline. Excess gingival display results in an unaesthetic smile, lip repositioning offers a comparatively simple solution for this problem. While the quality literature on this topic is limited statistical analysis of collected studies show that an estimated mean improvement of 3.4 mm can be achieved with surgical lip repositioning.

Percent weight reduction required to achieve minimal clinically important improvements in health-related quality of life among African Americans: A secondary analysis of the fit body and soul study.

OBJECTIVE: To calculate the percent weight reduction required to achieve minimal clinically important improvement (MCII) in health-related quality of life (HRQOL). DESIGN: Secondary data analysis from the longitudinal cohort of a single-blinded, cluster-randomized community trial to test the efficacy of the faith-based adaptation of the Diabetes Prevention Program. SETTING: African-American churches. PARTICIPANTS: This study included 472 congregants with a body mass index of ≥25 and fasting plasma glucose<126mg/dl. MAIN OUTCOME MEASURE: Percent weight reduction required to achieve the MCII in HRQOL measured by two instruments, SF-12 and EQ-5D, one year following baseline. ANALYSIS: The percent weight reduction required to achieve established MCII in SF-12 Physical Component Summary (PCS), SF-12 Mental Component Summary (MCS), and EQ-5D Health Status (HS) at one-year follow-up were calculated using fitted linear regression models. In addition to models for the total sample, we generated models, stratified by baseline BMI, PCS, and HS, to calculate the percent weight reduction required to achieve MCII in HRQOL for those most in need of weight reduction and those in need of improved HRQOL. RESULTS: The percent weight reduction was a significant predictor of improvement in the SF-12PCS and the EQ-5DHS but not SF-12MCS. To achieve a MCII in SF-12PCS and EQ-5DHS, 18% and 30% weight reductions were required, respectively. A smaller percent weight reduction was required when the baseline BMI was ≥40. CONCLUSIONS AND IMPLICATIONS: Improvements in HRQOL among African-American congregants seeking weight reduction required more than the 3-5% weight reduction associated with improvements in physical health.

Falls as Adverse Events in Psychosocial Treatment of Depression: Findings from a Clinical Trial in Nursing Homes.

Falls pose a significant health risk for nursing home residents and are associated with depression and medical treatments for depression. Data on falls as an adverse event to psychosocial treatments are lacking. We examined risk of falls as an adverse event in a clinical trial of a behavioral treatment for depression. Participants were 82 depressed nursing home residents. Adverse events were recorded at each research contact. We used the rate ratio based on the respective incidence densities in the treatment and control groups to measure association between fall rate and treatment. The treatment group had almost six times higher risk of falls than the control group, a statistically significant association. Findings suggest that it may be of value to include statistical analysis of falls as adverse events in trials of behavioral interventions for depression.