Automated, High-Throughput Platform to Generate a High-Reliability, Comprehensive Rectal Cancer Database.

PURPOSE: Dynamic operations platforms allow for cross-platform data extraction, integration, and analysis, although application of these platforms to large-scale oncology enterprises has not been described. This study presents a pipeline for automated, high-fidelity extraction, integration, and validation of cross-platform oncology data in patients undergoing treatment for rectal cancer at a single, high-volume institution. METHODS: A dynamic operations platform was used to identify patients with rectal cancer treated at MD Anderson Cancer Center between 2016 and 2022 who had magnetic resonance imaging (MRI) imaging and preoperative treatment details available in the electronic health record (EHR). Demographic, clinicopathologic, tumor mutation, radiographic, and treatment data were extracted from the EHR using a methodology adaptable to any disease site. Data accuracy was assessed by manual review. Accuracy before and after implementation of synoptic reporting was determined for MRI data. RESULTS: A total of 516 patients with localized rectal cancer were included. In the era after institutional adoption of synoptic reports, the dynamic operations platform extracted T (tumor) category data from the EHR with 95% accuracy compared with 87% before the use of synoptic reports, and N (lymph node) category with 88% compared with 58%. Correct extraction of pelvic sidewall adenopathy was 94% compared with 78%, and extramural vascular invasion accuracy was 99% compared with 89%. Neoadjuvant chemotherapy and radiation data were 99% accurate for patients who had synoptic data sources. CONCLUSION: Using dynamic operations platforms enables automated cross-platform integration of multiparameter oncology data with high fidelity in patients undergoing multimodality treatment for rectal cancer. These pipelines can be adapted to other solid tumors and, together with standardized reporting, can increase efficiency in clinical research and the translation of actionable findings toward optimizing patient outcomes.

Personal history of cancer as a risk factor for second primary lung cancer: Implications for lung cancer screening.

BACKGROUND: Personal history of cancer is an independent risk factor for lung cancer but is omitted from existing lung cancer screening eligibility criteria. In this study, we assess the lung cancer risk among cancer survivors and discuss potential implications for screening. METHODS: This was a retrospective, secondary analysis of data from the Surveillance, Epidemiology and End Results (SEER) registry and the MD Anderson Cancer Center (MDACC). We estimated the standardized incidence ratios (SIRs) for lung cancer by site of first primary cancer using data from SEER. We assessed the lung cancer risk among head and neck cancer survivors from MDACC using cumulative incidence and compared the risk ratios (RR) by individuals' screening eligibility status. RESULTS: Other than first primary lung cancer (SIR: 5.10, 95% CI: 5.01-5.18), cancer survivors in SEER with personal history of head and neck cancer (SIR: 3.71, 95% CI: 3.63-3.80) had the highest risk of developing second primary lung cancer, followed by bladder (SIR: 1.86, 95% CI: 1.81-1.90) and esophageal cancers (SIR: 1.78, 95% CI: 1.61-1.96). Head and neck cancer survivors had higher risk to develop lung cancer compared to the National Lung Screening Trial's subjects, (781 vs. 572 per 100,000 person-years, respectively). Head and neck cancer survivors ineligible for lung cancer screening seen at MDACC had significantly higher lung cancer risk than head and neck cancer survivors from SEER (RR: 1.9, p < 0.001). CONCLUSION: Personal history of cancer, primarily head and neck cancer, is an independent risk factor for lung cancer and may be considered as an eligibility criterion in future lung cancer screening recommendations.

Serum Tumor Markers and Outcomes in Patients With Appendiceal Adenocarcinoma.

Importance: Serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA125) have been useful in the management of gastrointestinal and gynecological cancers; however, there is limited information regarding their utility in patients with appendiceal adenocarcinoma. Objective: To assess the association of serum tumor markers (CEA, CA19-9, and CA125) with clinical outcomes and pathologic and molecular features in patients with appendiceal adenocarcinoma. Design, Setting, and Participants: This is a retrospective cohort study at a single tertiary care comprehensive cancer center. The median (IQR) follow-up time was 52 (21-101) months. Software was used to query the MD Anderson internal patient database to identify patients with a diagnosis of appendiceal adenocarcinoma and at least 1 tumor marker measured at MD Anderson between March 2016 and May 2023. Data were analyzed from January to December 2023. Main Outcomes and Measures: Association of serum tumor markers with survival in patients with appendiceal adenocarcinoma. Cox proportional hazards regression analyses were also performed to assess associations between clinical factors (serum tumor marker levels, demographics, and patient and disease characteristics) and patient outcomes (overall survival). Results: A total of 1338 patients with appendiceal adenocarcinoma were included, with a median (range) age at diagnosis of 56.5 (22.3-89.6) years. The majority of the patients had metastatic disease (1080 patients [80.7%]). CEA was elevated in 742 of the patients tested (56%), while CA19-9 and CA125 were elevated in 381 patients (34%) and 312 patients (27%), respectively. Individually, elevation of CEA, CA19-9, or CA125 were associated with worse 5-year survival; elevated vs normal was 81% vs 95% for CEA (hazard ratio [HR], 4.0; 95% CI, 2.9-5.6), 84% vs 92% for CA19-9 (HR, 2.2; 95% CI, 1.4-3.4), and 69% vs 93% for CA125 (HR, 4.6; 95% CI, 2.7-7.8) (P < .001 for all). Quantitative evaluation of tumor markers was associated with outcomes. Patients with highly elevated (top 10th percentile) CEA, CA19-9, or CA125 had markedly worse survival, with 5-year survival rates of 59% for CEA (HR, 9.8; 95% CI, 5.3-18.0), 64% for CA19-9 (HR, 6.0; 95% CI, 3.0-11.7), and 57% for CA125 (HR, 7.6; 95% CI, 3.5-16.5) (P < .001 for all). Although metastatic tumors had higher levels of all tumor markers, when restricting survival analysis to 1080 patients with metastatic disease, elevated CEA, CA19-9, or CA125 were all still associated worse survival (HR for CEA, 3.4; 95% CI, 2.5-4.8; P < .001; HR for CA19-9, 1.8; 95% CI, 1.2-2.7; P = .002; and HR for CA125, 3.9; 95% CI, 2.4-6.4; P < .001). Interestingly, tumor grade was not associated with CEA or CA19-9 level, while CA-125 was slightly higher in high-grade tumors relative to low-grade tumors (mean value, 18.3 vs 15.0; difference, 3.3; 95% CI, 0.9-3.7; P < .001). Multivariable analysis identified an incremental increase in the risk of death with an increase in the number of elevated tumor markers, with an 11-fold increased risk of death in patients with all 3 tumor markers elevated relative to those with none elevated. Somatic mutations in KRAS and GNAS were associated with significantly higher levels of CEA and CA19-9. Conclusions and Relevance: In this retrospective study of serum tumor markers in patients with appendiceal adenocarcinoma, CEA, CA19-9, and CA125 were associated with overall survival in appendiceal adenocarcinoma. Given their value, all 3 biomarkers should be included in the initial workup of patients with a diagnosis of appendiceal adenocarcinoma.

Practice Changes in Checkpoint Inhibitor-Induced Immune-Related Adverse Event Management at a Tertiary Care Center.

Understanding of immune-related adverse events (irAEs) has evolved rapidly, and management guidelines are continually updated. We explored temporal changes in checkpoint inhibitor-induced irAE management at a tertiary cancer care center to identify areas for improvement. We conducted a single-center retrospective study of patients who developed a gastrointestinal, pulmonary, renal, or cardiac irAE between July and 1 October in 2019 or 2021. We collected patient demographic and clinical information up to 1 year after toxicity. Endoscopic evaluation and specialty follow-up after discharge for patients with gastrointestinal irAEs declined between the 2019 and 2021 periods. Symptom duration and steroid taper attempts also declined. For pulmonary irAEs, rates of specialty consultation, hospital admission and readmission, and mortality improved in 2021 compared with 2019. Follow-up rates after hospital discharge were consistently low (<50%) in both periods. For cardiac irAEs, consultation with a cardiologist was frequent and prompt in both periods. Outpatient treatment and earlier specialty consultation improved outcomes with gastrointestinal irAEs. Our study exploring irAE practice changes over time identified areas to improve management; specifically, timely specialty consultation was associated with better outcomes for gastrointestinal irAEs. These findings can help improve the quality of management algorithms at our institution and may inform policies in other institutions.

The Clinical Significance of CEA, CA19-9, and CA125 in Management of Appendiceal Adenocarcinoma.

Importance: Serum tumor markers CEA, CA19-9, & CA125 have been useful in the management of gastrointestinal and gynecological cancers, however there is limited information regarding their utility in patients with appendiceal adenocarcinoma. Objective: Assessing the association of serum tumor markers (CEA, CA19-9, and CA125) with clinical outcomes, pathologic, and molecular features in patients with appendiceal adenocarcinoma. Design: This is a retrospective study with results reported in 2023. The median follow-up time was 43 months. Setting: Single tertiary care comprehensive cancer center. Participants: Under an approved Institutional Review Board protocol, the Palantir Foundry software system was used to query the MD Anderson internal patient database to identify patients with a diagnosis of appendiceal adenocarcinoma and at least one tumor marker measured at MD Anderson between 2016 and 2023. Results: A total of 1,338 patients with appendiceal adenocarcinoma were included, with a median age of 56.5 years. The majority of the patients had metastatic disease (80.7%). CEA was elevated in more than half of the patients tested (56%), while CA19-9 and CA125 were elevated in 34% and 27%, respectively. Individually, elevation of CEA, CA19-9, or CA125 were associated with worse 5-year survival; 82% vs 95%, 84% vs 92%, and 69% vs 93% elevated vs normal for CEA, CA19-9, and CA125 respectively (all p<0.0001). Quantitative evaluation of tumor markers increased prognostic ability. Patients with highly elevated (top 10th percentile) CEA, CA19-9 or CA125 had markedly worse survival with 5-year survival rates of 59%, 64%, and 57%, respectively (HR vs. normal : 9.8, 6.0, 7.6, all p<0.0001). Although metastatic tumors had higher levels of all tumor markers, when restricting survival analysis to 1080 patients with metastatic disease elevated CEA, CA19-9 or CA125 were all still associated worse survival (HR vs. normal : 3.4, 1.8, 3.9, p<0.0001 for CEA and CA125, p=0.0019 for CA19-9). Interestingly tumor grade was not associated with CEA or CA19-9 level, while CA-125 was slightly higher in high relative to low-grade tumors (18.3 vs. 15.0, p=0.0009). Multivariable analysis identified an incremental increase in the risk of death with an increase in the number of elevated tumor markers, with a 11-fold increased risk of death in patients with all three tumor markers elevated relative to those with none elevated. Mutation in KRAS and GNAS were associated with significantly higher levels of CEA and CA19-9. Conclusions: These findings demonstrate the utility of measuring CEA, CA19-9, and CA125 in the management of appendiceal adenocarcinoma. Given their prognostic value, all three biomarkers should be included in the initial workup of patients diagnosed with appendiceal adenocarcinoma.

Role of circulating mitochondria in venous thrombosis in glioblastoma.

BACKGROUND: Many patients with glioblastoma multiforme (GBM) develop deep venous thrombosis or pulmonary emboli. Cell-free circulating mitochondria increase after brain injury and are associated with coagulopathy. OBJECTIVES: This study evaluated whether mitochondria play a role in the GBM-induced hypercoagulable state. METHODS: We examined the correlation between cell-free circulating mitochondria and venous thrombosis in patients with GBM and the impact of mitochondria on venous thrombosis in mice with inferior vena cava stenosis. RESULTS: Using plasma samples of 82 patients with GBM, we found that patients with GBM had a higher number of mitochondria in their plasma (GBM with venous thromboembolism [VTE],: 2.8 × 107 mitochondria/mL; GBM without VTE, 1.9 × 107 mitochondria/mL) than that in healthy control subjects (n = 17) (0.3 × 107 mitochondria/mL). Interestingly, patients with GBM and VTE (n = 41) had a higher mitochondria concentration than patients with GBM without VTE (n = 41). In a murine model of inferior vena cava stenosis, intravenous delivery of mitochondria resulted in an increased rate of venous thrombosis compared with that in controls (70% and 28%, respectively). Mitochondria-induced venous thrombi were neutrophil-rich and contained more platelets than those in control thrombi. Furthermore, as mitochondria are the only source of cardiolipin in circulation, we compared the concentration of anticardiolipin immunoglobulin G in plasma samples of patients with GBM and found a higher concentration in patients with VTE (optical density, 0.69 ± 0.04) than in those without VTE (optical density, 0.51 ± 0.04). CONCLUSION: We concluded that mitochondria might play a role in the GBM-induced hypercoagulable state. We propose that quantifying circulating mitochondria or anticardiolipin antibody concentrations in patients with GBM might identify patients at increased risk of VTE.

Clinical implications of tumor-based next-generation sequencing in high-grade epithelial ovarian cancer.

BACKGROUND: Tumor-based next-generation sequencing is used inconsistently as a tool to tailor treatment of ovarian cancer, yet beyond detection of somatic BRCA1 and BRCA2 mutations, the clinical benefit is not well established. This study aimed to assess the clinical relevance of tumor-based next-generation sequencing (tbNGS) in patients with ovarian cancer. METHODS: This retrospective study included patients with high-grade epithelial ovarian carcinoma. tbNGS results were identified in the electronic medical record using optical character recognition and natural language processing. Genetic, clinical, and demographic information was collected. Progression-free survival (PFS) and overall survival were calculated and compared using log-rank tests. Multivariate Cox regression and clustering analyses were used to identify patterns of genetic alterations associated with survival. RESULTS: Of 1092 patients in the described population, 409 (37.5%) had tbNGS results. Nearly all (96.1% [393/409]) had one or more genetic alterations. In 25.9% (106/409) of patients, an alteration that aligned with a targeted treatment was identified, and in an additional 48.7% (199/409), tbNGS results suggested eligibility for an investigational agent or clinical trial. The most frequent alterations were TP53, PIK3CA, and NF1 mutations, and CCNE1 amplification. Together, BRCA1 and BRCA2 mutations were associated with longer PFS (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.42-0.92; p = .02), whereas AKT2 amplification was associated with shorter PFS (HR, 3.86; 95% CI, 1.002-14.88; p < .05). Multivariate Cox regression and clustering analyses identified several combinations of genetic alterations that corresponded to outcomes in patients with high-grade serous carcinoma. CONCLUSIONS: tbNGS often yields clinically relevant information. Detailed analysis of population-level tumor genomics may help to identify therapeutic targets and guide development of clinical decision support tools. PLAIN LANGUAGE SUMMARY: Although more and more patients with ovarian cancer are undergoing tumor-based next-generation sequencing to identify genetic mutations in their tumors, the benefits of such testing are not well established. In a group of over 400 patients with ovarian cancer who underwent tumor-based next-generation sequencing in the course of their treatment, nearly all patients had one or more genetic alterations detected, and one out of four patients had a mutation that qualified them for a personalized treatment option.

Current curricular trends after the COVID-19 pandemic: A national survey of psychiatry residency programs.

OBJECTIVES: During the COVID-19 pandemic, many psychiatry residencies (academic, community, and hybrid programs) have adopted different learning modalities to preserve a high quality of educational training. There is minimal data on specific program adaptations, related change perspectives, and program type stratification. This study sought to examine trends in curriculum changes in accredited psychiatry residency programs in the United States. METHODS: Program directors of accredited general psychiatry programs in the United States were surveyed to assess both general program details and changes in educational content, delivery, and perspectives with regard to program curricula. RESULTS: A total of 63 program directors out of 264 eligible programs completed the questionnaire (23.9%). There was a significant shift to integrate virtual learning post-pandemic (98.5%) compared to pre-pandemic (3%). However, there was no association between these modality changes and program type (p = 0.13). Furthermore, changes were noted with respect to didactic content (60%), decreased rotation sites (38%), and increased telemedicine exposure (84%) with no change of wellness days (67%) or protected time (97%). Again, the above changes had no association with program type. Use of virtual educational platforms was described as positive (59.7%) with 9 programs noting a future transition to a hybrid learning model for didactics and grand rounds. CONCLUSIONS: The findings suggest that pandemic-related curriculum adaptations occurred in all different types of psychiatry residencies and suggest a national trend to continue virtual educational platforms with regard to psychiatry didactics. However, future investigation of effectiveness of virtual learning programs in psychiatry residencies is warranted.

Self-reported and pill count measures of adherence to oral HIV PrEP among female sex workers living in South-Western Uganda.

BACKGROUND: Female sex workers (FSWs) in Uganda are at high risk of HIV infection. Scaling up oral pre-exposure prophylaxis (PrEP) will reduce HIV incidence if high levels of adherence are maintained. This study evaluates PrEP adherence using clinic-based pill counts and self-reported measures, and factors associated with protective levels of adherence. METHODS: Participants were sex workers who had been taking PrEP for at least 5 months and were attending routine follow-up visits for PrEP care in fishing communities and along the Trans-African Highway. Participants who had a pill count showing at least 85% use since their last clinic visit and those who reported taking their PrEP every day in the last 5 months were categorised as having 'protective adherence'. Spearman's correlation and weighted kappa assessed the relationship between pill count and self-reported measures. Bivariate and multivariate logistic regression was used to determine factors associated with protective adherence as measured by pill count. RESULTS: We recruited 524 FSWs, with a median age of 29 years (IQR 23-35). Participants were recruited from fishing communities and Trans-African Highway towns (n = 297, 56.7%, and n = 227, 43.0%). Nearly three quarters (n = 372, 71.0%) of women were estimated to have protective adherence based on pill count (i.e., a pill count of >85%) and 50.4% by self-report in last 3 months. There was a strong positive association between self-reported measures and pill count measures (rest = 0.6453, 95% CI = 0.5924-0.6927) and a moderate agreement between self-reported measures and pill count measures, κ = 0.544 (95%CI = 0.4869-0.6011, p < 0.001). Factors associated with protective adherence included being aged 35 years or older (aOR = 2.40, 95% CI = 1.17-4.86), living in a fishing community (aOR = 1.45, 95% CI = 0.62-3.38), and having an STI in last 3 months (aOR = 1.64, 95% CI = 1.07-2.49). CONCLUSION: Our findings indicate that PrEP-experienced FSWs attending clinical follow-up visits reported high protective levels of oral pre-exposure prophylaxis, as measured by both pill count and self-reported measures, and a moderate agreement between pill count and self-reported measures.

Association between abnormal lipid profile and inflammation and progression of myelodysplastic syndrome to acute leukemia.

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with a small risk of developing hematologic malignancies and a higher risk of cardiovascular diseases (CVD). We asked whether the reverse correlation exists and cardiometabolic risk factors have an impact on the progression of myelodysplastic syndrome (MDS) to acute myeloid leukemia (AML). We investigated the association between abnormal lipid profiles and inflammation in MDS, which shares many genetic mutations with CHIP, and the risk of developing acute leukemia. We examined the medical records of 11071 MDS patients. Among them, 5422 had at least one lipid profile or C-reactive protein (CRP) measurement. In univariate and multivariate analyses, elevated triglyceride and high-sensitive C-reactive protein (HS-CRP) were significantly associated with a diagnosis of acute leukemia in MDS patients. Next, we examined these associations in patients with available MDS prognostic scores (International Prognostic Scoring System, IPSS, or its revised version IPSS/R) (n = 2786 patients). We found that the statistical association between CRP and the progression of MDS to leukemia was independent of other variables in the scoring system. MDS patients with elevated CRP in both the high-risk and low-risk groups had a higher risk of progression to AML than those with a lower CRP. We speculate that inflammation might be a common denominator in developing hematologic malignancies and CVD in patients with clonal hematopoiesis.

Peripheral Interleukin-18 is negatively correlated with abnormal brain activity in patients with depression: a resting-state fMRI study.

BACKGROUND: Interleukin-18 (IL-18) may participate in the development of major depressive disorder, but the specific mechanism remains unclear. This study aimed to explore whether IL-18 correlates with areas of the brain associated with depression. METHODS: Using a case-control design, 68 subjects (34 patients and 34 healthy controls) underwent clinical assessment, blood sampling, and resting-state functional Magnetic Resonance Imaging (fMRI). The total Hamilton depression-17 (HAMD-17) score was used to assess depression severity. Enzyme-linked immunosorbent assay (ELISA) was used to detect IL-18 levels. Rest-state fMRI was conducted to explore spontaneous brain activity. RESULTS: The level of IL-18 was higher in patients with depression in comparison with healthy controls. IL-18 was negatively correlated with degree centrality of the left posterior cingulate gyrus in the depression patient group, but no correlation was found in the healthy control group. CONCLUSION: This study suggests the involvement of IL-18 in the pathophysiological mechanism for depression and interference with brain activity.

Interaction between the BDNF gene rs16917237 polymorphism and job stress on job burnout of Chinese university teachers.

BACKGROUND: Job burnout is related to both environmental and genetic factors. However, previous studies on job burnout in teachers have mainly focused on potential stressors in the environment, while ignoring genetic factors. Brain-derived neurotrophic factor (BNDF) may be a pathogenic factor involved in burnout symptoms. Therefore, this study further investigated the relationship between the BNDF gene polymorphism, job stress and job burnout in Chinese university teachers. METHODS: Using a cross-sectional design, 361 faculty and staff members from a university in Beijing were enrolled. Job stress was measured with the Work Stress Scale. Job burnout was measured by the Chinese version of the Maslach Burnout Inventory which has three dimensions, namely emotional exhaustion (EE), cynicism (CY), and reduced personal accomplishment (PA). The BDNF gene rs16917237 polymorphism was genotyped in all participants. RESULTS: CY score was associated with education level (p < 0.01), and PA score was associated with age (p < 0.05). Job stress was positively correlated with EE (r = 0.776), CY (r = 0.457), and PA (r = 0.163) (all p < 0.01). After controlling for gender, age and education level, the BDNF gene rs16917237 polymorphism did not affect job burnout, but it interacted with job stress to influence EE and CY (both p < 0.05), indicating that individuals with TT genotype were more susceptible to higher levels of job stress, resulting in job burnout symptoms. CONCLUSIONS: Our results suggest that the BDNF gene rs16917237 TT genotype may be a risk factor for job burnout in Chinese university teachers.

Benefit-Risk Assessment of Psychotropic Drugs in Older Patients with Chronic Obstructive Pulmonary Disease.

Depression, anxiety, and other mental health disorders, including bipolar disorder and schizophrenia, occur commonly in older adults with chronic obstructive pulmonary disease (COPD), and they are often inadequately treated. We review the available evidence for benefits and risks of pharmacologic treatments (e.g. selective serotonin reuptake inhibitors [SSRIs], serotonin-noradrenaline reuptake inhibitors [SNRIs], tricyclic antidepressants [TCAs], antipsychotic drugs, and benzodiazepines) for common mental illnesses in older persons with COPD. Evidence to use both SSRIs/SNRIs and TCAs from randomized controlled trials is uncertain for treating major depression in patients with COPD. However, population-based findings indicate that they are widely used, and this valuable intervention (preferably SSRIs/SNRIs) should not be denied for selected patients after evaluating potential risks and benefits, especially patients presenting with major depression and suicidal ideation, when a collaborative-care approach is being used. Although there is some evidence for the short-term use of benzodiazepines for treating insomnia, breathlessness, and anxiety in patients with COPD, their long-term use should be closely monitored or avoided to reduce the increased rate of major adverse events. Currently, there are only limited data on the use of antipsychotic drugs for managing schizophrenia or bipolar disorder in older patients with COPD. Hence, clinicians should use extra caution when prescribing antipsychotic agents and be vigilant for symptoms of acute respiratory failure and other adverse effects. Psychotropic medications are clearly beneficial for younger, healthy persons with depression and anxiety; however, the risk-benefit calculation is not so clear for treating psychological problems, schizophrenia, and bipolar disorder in older adults with COPD, given older-adult sensitivity to medications and the mixed findings of relatively few controlled trials.

Haloperidol-induced isolated lingual dystonia.

A 28-year-old woman presenting with agitation and mania with psychotic features developed symptoms of isolated lingual dystonia shortly after the initiation of a haloperidol concentrate regimen.

Cognitive Behavioral Therapy for Mood and Insomnia in Persons With Dementia: A Systematic Review.

BACKGROUND: Cognitive behavioral therapy (CBT) is a goal-oriented intervention that aims to improve detrimental emotional or behavioral distress by modifying individuals' thought processes. This review evaluates the efficacy and specific adaptations of CBT in persons with mild cognitive impairment and dementia. METHODS: A literature search of PubMed, Embase, and PsycINFO was conducted up to March 2020. Study quality was assessed using the Cochrane risk of bias criteria. RESULTS: Twelve publications were identified. Seven of the studies demonstrated CBT efficacy to improve depression, anxiety, and/or quality of life. One study's positive postintervention outcome became insignificant with longer term follow up. Two of the studies improved sleep outcomes. Four studies integrated caregivers into intervention delivery. Three studies utilized content, memory, and adherence adaptations aimed to improve intervention efficacy. Two studies included adaptations to address caregiver burden and depression. CONCLUSION: There is strong evidence to suggest that CBT is associated with improvements in anxiety, depression, and quality of life in persons with mild cognitive impairment and dementia. CBT showed a reduction in insomnia and improvements in sleep quality. However, there is insufficient evidence to draw conclusions on the effects of CBT on insomnia. These results suggest that further investigation into insomnia outcomes is needed.

Piercing the Overcast.

In this narrative medicine essay1, a medical student recounts how his adversities with patient connection as a former psychiatric technician created a fortuitous collateral beauty.

Characteristics of gay and bisexual men who rarely use HIV risk reduction strategies during condomless anal intercourse: Results from the FLUX national online cohort study.

PURPOSE: To understand the characteristics of a minority of Australian gay and bisexual men (GBM) who, despite an increase in the number and availability of HIV risk reduction strategies, do not consistently use a strategy to protect themselves from HIV. METHODS: This analysis is based on data from 2,920 participants in a national, online, prospective observational cohort study. GBM who never or rarely used HIV risk reduction strategies (NRR) were compared with two groups using multivariate logistic regression: i) GBM using pre-exposure prophylaxis (PrEP) and ii) GBM frequently using risk reduction strategies (FRR) other than PrEP. RESULTS: Compared to PrEP users, NRR men were younger (p<0.0001), less socially engaged with gay men (p<0.0001) and less likely to have completed a postgraduate (p<0.05) or undergraduate degree (p<0.05). They were also less likely to have recently used amyl nitrite (p<0.05), erectile dysfunction medication (p<0.05) and cocaine (p<0.05) in the previous 6 months. Compared with FRR men, NRR men were less likely to have completed a postgraduate (p<0.0001) or undergraduate degree (p<0.05), scored higher on the sexual sensation-seeking scale (p<0.0001) and were more likely to identify as versatile (p<0.05), a bottom (p<0.05) or very much a bottom (p<0.05) during anal sex. CONCLUSIONS: NRR men were largely similar to other Australian GBM. However, our analysis suggests it may be appropriate to focus HIV prevention interventions on younger, less socially engaged and less educated GBM, as well as men who prefer receptive anal intercourse to promote the use of effective HIV risk reduction strategies.