Allergy History and Immunotherapy Response in Patients With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: This study examines the association between patient-reported allergy history and immune checkpoint inhibition (ICI) response in patients with recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC). STUDY DESIGN: Retrospective cohort study. SETTING: Academic tertiary care hospital. METHODS: Data were collected from the electronic medical records on baseline age, sex, allergy history, human papillomavirus status, T-stage, N-stage, smoking status, and survival for patients with and without an allergy history. The primary outcome was ICI response defined as complete or partial response by the RECIST criteria. Chi-square and logistic regression analyses were conducted to compare rates and odds of ICI response. Kaplan-Meier analyses were used to compare survival between groups. RESULTS: Our study included 52 patients with an allergy history and 36 patients without an allergy history. The groups were similar in age, sex, HPV status, smoking status, and T- and N-stage. Patients with an allergy history (17/52, 32.1%) had a greater ICI response rate than patients without allergy history (4/36, 11.1%) (P = .02). After adjusting for HPV, patients with allergies had 3.93 (1.19-13.00) times increased odds of ICI response compared to patients without allergies. The median progression-free survival was 6.0 and 4.2 months for patients with and without an allergy history respectively (log-rank, P = .04). The median overall survival was 25.0 and 11.1 months for patients with and without an allergy history respectively (log-rank, P = .002). CONCLUSION: Patient-reported allergy history was associated with ICI response in patients with RMHNSCC, underscoring the potential clinical utility of allergy history in estimating ICI response.

Conserved spatiotemporal expression landscape of dominant tRNA genes in human and mouse.

Transfer RNAs are integral for protein synthesis and the interpretation of the information contained in DNA. To date, a few methods, including custom microarrays and custom targeted sequencing, have been used to quantify tRNA. However, methods using available RNA-sequencing data have not yet been reported. We created a bioinformatics pipeline to quantify the highly expressed tRNAs in RNA-Seq effectively, demonstrated by the preserved ratio of the expression levels of two massively duplicated tRNAAla genes in mouse. Using this quantification, we examined the tRNA expression with relation to tissue type and developmental stage in both human and mouse. Heart exhibited the highest overall tRNA expression for both human and mouse. Furthermore, tRNA expression grew to a peak before decreasing steadily with developmental stage, a trend that was conserved in both human and mouse. The two mitochondrial tRNA genes, tRNASer(TCA)(m) and tRNALeu(TTA)(m), which partly contribute to these trends, have been attributed to various human diseases. The tissue-specific high expression of tRNAGln(CAG) and tRNAGln(CAA) in human brains, especially in hindbrain and cerebellum, suggests their important roles in neurological disorders. In summary, our approach revealed conserved spatiotemporal expression of highly expressed tRNAs in both human and mouse. Our method can be applied to other RNA-Seq data to examine the roles of these tRNAs in different human diseases or scientific studies.

Impact of comorbidities on outcomes in patients with advanced head and neck cancer undergoing immunotherapy.

OBJECTIVES: To explore the impact of pre-existing comorbidities on immunotherapy response, overall and progression-free survival, and immune-related adverse events (irAEs) of patients with advanced head and neck cancer (HNC) treated with immunotherapy. PATIENTS AND METHODS: Ninety-three patients treated with immunotherapy were identified and stratified into comorbidity absent or present (CCI < 1 and CCI ≥ 1, respectively) cohorts, and clinical outcomes were compared between these two groups. RESULTS: Patients with no comorbidities had longer overall survival (aHR = 2.74, 95% CI [1.18, 6.40], p = 0.02) and progression-free survival (aHR = 2.07, 95% CI [1.03, 4.16], p = 0.04) and a higher tumor response rate (32% in CCI < 1 vs. 14% in CC ≥ 1, p = 0.05). Risk for irAEs was higher in the comorbidity absent group (p = 0.05). CONCLUSION: Comorbidity should be considered as a significant prognostic factor in clinical decision-making for patients with advanced HNC undergoing immunotherapy.

Tumor Histological Grade and Immunotherapy Response in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

Importance: Tumor histological factors that predict immunotherapy response in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are not well defined. Objective: To investigate the association between tumor grade and immunotherapy response in patients with recurrent or metastatic mucosal HNSCC. Design, Setting, and Participants: In this retrospective cohort study, the medical records of 60 patients with recurrent or metastatic mucosal HNSCC treated with immune checkpoint inhibitors at Johns Hopkins Hospital between July 1, 2015, and January 22, 2020, were reviewed. Exposures: High-grade tumors (HGTs) vs low-grade tumors (LGTs) in recurrent or metastatic HNSCC. Main Outcomes and Measures: Patients were divided into 2 groups: those with LGTs (well differentiated and moderately differentiated) and those with HGTs (poorly differentiated). The main outcome was a clinically beneficial immunotherapy response, defined as complete response or partial response. Univariable and multivariable logistic regressions were conducted to calculate odds ratios for each variable's association with immunotherapy response. Survival differences were evaluated using Kaplan-Meier survival curves with multivariable Cox proportional hazards regression models. Results: The 60 patients (35 with HGTs and 25 with LGTs) had a mean (SD) age of 64.6 (8.88) years; 51 were male (85%); and 38 were current or former smokers (63%). The oropharynx was the most common primary tumor site both in patients with HGTs (22 of 35; 63%) and those with LGTs (12 of 25; 48%). Bivariate analysis showed the proportion of patients having a beneficial response to immunotherapy was greater for patients with HGTs (12 of 35; 34.3%) than those with LGTs (2 of 25, 8.0%) (difference, 26.3%; 95% CI, 7.3%-45.3%). Upon multivariable analysis, patients with HGTs had 5.35-fold increased odds (95% CI, 1.04-27.37) of having a clinically beneficial response to immunotherapy. Among patients with available tumor genomic profiling data, the mean tumor mutational burden was greater for patients with HGTs (mean [SD], 8.6 [5.4] mut/Mb; n = 8) than patients with LGTs (mean [SD], 3.6 [1.1] mut/Mb; n = 4) (difference = 5.0 mut/Mb; 95% CI -1.4 to 11.4 mut/Mb; Cohen d = 1.2). Conclusions and Relevance: In this cohort study, tumor grade was independently associated with immunotherapy response in patients with recurrent or metastatic mucosal HNSCC. These findings highlight the potential role of tumor grade in predicting immunotherapy response in mucosal HNSCC.

Nutritional Status as a Predictive Biomarker for Immunotherapy Outcomes in Advanced Head and Neck Cancer.

The association between pretreatment nutritional status and immunotherapy response in patients with advanced head and neck cancer is unclear. We retrospectively analyzed a cohort of 99 patients who underwent treatment with anti-PD-1 or anti-CTLA-4 antibodies (or both) for stage IV HNSCC between 2014 and 2020 at the Johns Hopkins Hospital. Patient demographics and clinical characteristics were retrieved from electronic medical records. Baseline prognostic nutritional index (PNI) scores and pretreatment body mass index (BMI) trends were calculated. Associations between PNI and BMI were correlated with overall survival (OS), progression-free survival (PFS), and immunotherapy response. In univariate analysis, there was a significant correlation between OS and PFS with baseline PNI (OS: HR: 0.464; 95% CI: 0.265-0.814; PFS: p = 0.007 and HR: 0.525; 95% CI: 0.341-0.808; p = 0.003). Poor OS was also associated with a greater decrease in pretreatment BMI trend (HR: 0.42; 95% CI: 0.229-0.77; p = 0.005). In multivariate analysis, baseline PNI but not BMI trend was significantly associated with OS and PFS (OS: log (HR) = -0.79, CI: -1.6, -0.03, p = 0.041; PFS: log (HR) = -0.78, CI: -1.4, -0.18, p = 0.011). In conclusion, poor pretreatment nutritional status is associated with negative post-immunotherapy outcomes.

Emergency Department Screening for Unhealthy Alcohol and Drug Use with a Brief Tablet-Based Questionnaire.

BACKGROUND: Screening for unhealthy alcohol and drug use in the emergency department (ED) can be challenging due to crowding, lack of privacy, and overburdened staff. The objectives of this study were to determine the feasibility and utility of a brief tablet-based screening method in the ED and if patients would consider a face-to-face meeting with a certified alcohol and drug counselor (CADC) for more in-depth screening, brief intervention, and referral to treatment (SBIRT) helpful via this interface. METHODS: A tablet-based questionnaire was offered to 500 patients. Inclusion criteria were age ≥18, Emergency Severity Index 2-5, and English comprehension. Subjects were excluded if they had evidence of acute intoxication and/or received sedating medication. RESULTS: A total of 283 (57%) subjects were enrolled over a 4-week period, which represented an increase of 183% over the monthly average of patients referred for SBIRT by the CADC prior to the study. There were 131 (46%) who screened positive for unhealthy alcohol and drug use, with 51 (39%) and 37 (28%) who screened positive for solely unhealthy alcohol use and drug use/drug use disorders, respectively. There were 43 (33%) who screened positive for combined unhealthy alcohol and drug use. Despite willingness to participate in the tablet-based questionnaire, only 20 (15%) with a positive screen indicated via the tablet that a face-to-face meeting with the CADC for further SBIRT would be helpful. CONCLUSION: Brief tablet-based screening for unhealthy alcohol and drug use in the ED was an effective method to increase the number of adult patients identified than solely by their treating clinicians. However, only a minority of subjects screening positive using this interface believed a face-to-face meeting with the CADC for further SBIRT would be helpful.

Cerebrovascular risks with rapid blood pressure lowering in the absence of hypertensive emergency.

STUDY OBJECTIVE: In the Emergency Department (ED) setting, clinicians commonly treat severely elevated blood pressure (BP) despite the absence of evidence supporting this practice. We sought to determine if this rapid reduction of severely elevated BP in the ED has negative cerebrovascular effects. METHODS: This was a prospective quasi-experimental study occurring in an academic emergency department. The study was inclusive of patients with a systolic BP (SBP) > 180 mm Hg for whom the treating clinicians ordered intensive BP lowering with intravenous or short-acting oral agents. We excluded patients with clinical evidence of hypertensive emergency. We assessed cerebrovascular effects with measurements of middle cerebral artery flow velocities and any clinical neurological deterioration. RESULTS: There were 39 patients, predominantly African American (90%) and male (67%) and with a mean age of 50 years. The mean pre-treatment SBP was 210 ±â€¯26 mm Hg. The mean change in SBP was -38 mm Hg (95% CI -49 to -27) mm Hg. The average change in cerebral mean flow velocity was -5 (95% CI -7 to -2) cm/s, representing a -9% (95% CI -14% to -4%) change. Two patients (5.1%, 95% CI 0.52-16.9%) had an adverse neurological event. CONCLUSION: While this small cohort did not find an overall substantial change in cerebral blood flow, it demonstrated adverse cerebrovascular effects from rapid BP reduction in the emergency setting.

Paraneoplastic Hyperleukocytosis in Pancreatic Adenocarcinoma.

Background: Paraneoplastic hyperleukocytosis is a rare phenomenon observed in patients with adenocarcinomas and other malignancies. In this study, we present a case of paraneoplastic hyperleukocytosis in pancreatic adenocarcinoma secondary to excessive secretion of serum granulocyte colony-stimulating factor (G-CSF). Presentation: We report a 71-year-old Caucasian male who presented to our hospital with hyperleukocytosis in the setting of locally advanced pancreatic adenocarcinoma. The patient was recently diagnosed 4 months before presentation and received abraxane/gemcitabine in addition to palliative radiation therapy for continued gastrointestinal bleeding. During routine laboratory assessment, the patient was found to have a white blood cell (WBC) count of 153 K/UL (75% neutrophils and 14% bands). Bone marrow biopsy and cytology were negative for neoplastic features. Serum G-CSF levels returned markedly elevated, supporting the diagnosis of paraneoplastic hyperleukocytosis. Interestingly, the WBC count decreased significantly following each of two cycles of chemotherapy, further suggesting a paraneoplastic etiology of hyperleukocytosis. The patient did not receive any growth factor support at any point before or during treatment. Conclusion: In conclusion, the presence of hyperleukocytosis in cancer should raise clinical suspicion of a paraneoplastic phenomenon when other possible causes have been excluded. Hyperleukocytosis in this setting may correlate with progression of disease and lessen with treatment.

Two SNAP-25 genetic variants in the binding site of multiple microRNAs and susceptibility of ADHD: A meta-analysis.

The aim of this meta-analysis is to assess the associations between two most widely investigated polymorphisms (rs3746544 and rs1051312) in the 3'UTR of the SNAP-25 gene and susceptibility of ADHD. Two investigators selected related studies and assessed methodological quality independently. Six studies were included in this meta-analysis for a total of 715 cases and 655 controls. There is no apparent association between rs3746544 polymorphisms and risk of ADHD. However, subgroup analysis based on ethnicity demonstrated a strong association between rs3746544 polymorphism and ADHD in the subset of Asian participants, but not among Caucasians. Compared to the T allele, the allele G was associated with a significantly decreased risk of developing ADHD in the Asian population (odds ratio (OR) = 0.70, 95% confidence interval (CI) = 0.52-0.95, p = 0.02). The association between the TT genotype and ADHD risk was also significantly increased as compared to G/T (OR = 1.56, 95% CI = 1.00-2.44, p = 0.05) and the dominant genetic model (GG + GT vs. TT: OR = 1.51, 95% CI = 1.07-2.13, p = 0.02). For the rs1051312 SNP, being homozygous for the minor allele (C/C) was associated with a 3.66 higher odds of ADHD as compared to cases homozygous for the major allele (T/T) (95% CI = 1.64-8.13, p = 0.001), and 3.57 higher odds as compared to heterozygous (C/T) carriers (95% CI = 2.01-12.90, p < 0.001). Our results suggest that the polymorphisms rs3746544 and rs1051312 may increase the odds of developing ADHD. Additional studies are needed to confirm these findings.

Effect of actionable somatic mutations on racial/ethnic disparities in head and neck cancer prognosis.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and minorities have the worst survival. However, the molecular mechanisms underlying survival disparities have not been elucidated. METHODS: In a retrospective study, we assessed association between HNSCC early death (<2 years) and 208 somatic mutations of 10 cancer-related genes in 214 patients: 98 non-Hispanic whites (46%), 72 Hispanic whites (34%), and 44 African Americans (20%). RESULTS: Hispanic whites and African Americans had significantly higher mutation rates for EGFR, HRAS, KRAS, and TP53. HNSCC early death was significantly associated with 3+ mutations (odds ratio [OR] = 2.78, 95% confidence interval [CI] = 1.16, 6.69), NOTCH1 mutations in non-Hispanic whites (OR = 5.51; 95% CI = 1.22-24.83) and TP53 mutations in Hispanic whites (OR = 3.84; 95% CI = 1.08-13.68) in multivariable analysis adjusted for age, sex, tumor site, and tumor stage. CONCLUSION: We have provided the proof-of-principal data to link racial/ethnic-specific somatic mutations and HNSCC prognosis and pave the way for precision medicine to overcome HNSCC survival disparities. © 2016 Wiley Periodicals, Inc. Head Neck 38:1234-1241, 2016.

Determining the Cost-Savings Threshold for HIV Adherence Intervention Studies for Persons with Serious Mental Illness and HIV.

Persons with serious mental illnesses are at increased risk for contracting and transmitting HIV and often have poor adherence to medication regimens. Determining the economic feasibility of different HIV adherence interventions among individuals with HIV and serious mental illness is important for program planners who must make resource allocation decisions. The goal of this study was to provide a methodology to estimate potential cost savings from an HIV medication adherence intervention program for a new study population, using data from prior published studies. The novelty of this approach is the way CD4 count data was used as a biological marker to estimate costs averted by greater adherence to anti-retroviral treatment. Our approach is meant to be used in other adherence intervention studies requiring cost modeling.

Combining boundary-based methods with tensor-based morphometry in the measurement of longitudinal brain change.

Tensor-based morphometry is a powerful tool for automatically computing longitudinal change in brain structure. Because of bias in images and in the algorithm itself, however, a penalty term and inverse consistency are needed to control the over-reporting of nonbiological change. These may force a tradeoff between the intrinsic sensitivity and specificity, potentially leading to an under-reporting of authentic biological change with time. We propose a new method incorporating prior information about tissue boundaries (where biological change is likely to exist) that aims to keep the robustness and specificity contributed by the penalty term and inverse consistency while maintaining localization and sensitivity. Results indicate that this method has improved sensitivity without increased noise. Thus it will have enhanced power to detect differences within normal aging and along the spectrum of cognitive impairment.

Changes in hospital nurse work environments and nurse job outcomes: an analysis of panel data.

BACKGROUND: One strategy proposed to alleviate nursing shortages is the promotion of organizational efforts that will improve nurse recruitment and retention. Cross-sectional studies have shown that the quality of the nurse work environment is associated with nurse outcomes related to retention, but there have been very few longitudinal studies undertaken to examine this relationship. OBJECTIVES: To demonstrate how rates of burnout, intention to leave, and job dissatisfaction changed in a panel of hospitals over time, and to explore whether these outcomes were associated with changes in nurse work environments. METHODS: A retrospective, two-stage panel design was chosen for this study. Survey data collected from large random samples of registered nurses employed in Pennsylvania hospitals in 1999 and 2006 were used to derive hospital-level rates of burnout, intention to leave current position, and job dissatisfaction, and to classify the quality of nurses' work environments at both points in time. A two-period difference model was used to estimate the dependence of changes in rates of nurse burnout, intention to leave, and job dissatisfaction on changes in nurse work environments between 1999 and 2006 in 137 hospitals, accounting for concurrent changes in nurse staffing levels. RESULTS: In general, nurse outcomes improved between 1999 and 2006, with fewer nurses reporting burnout, intention to leave, and job dissatisfaction in 2006 as compared to 1999. Our difference models showed that improvements in work environment had a strong negative association with changes in rates of burnout (ß=-6.42%, p<0.01) intention to leave (ß=-4.10%, p<0.01), and job dissatisfaction (ß=-8.00%, p<0.01). CONCLUSIONS: Improvements in nurse work environments over time are associated with lower rates of nurse burnout, intention to leave current position, and job dissatisfaction.

Nursing practice environment and outcomes for oncology nursing.

BACKGROUND: It is commonly assumed that oncology nurses experience high job-related burnout and high turnover because their work involves inherent stressors such as caring for patients with serious and often life-threatening illness. OBJECTIVES: The objectives of this study were to examine the differences in outcomes such as job dissatisfaction and burnout between oncology nurses and medical-surgical nurses, and to identify factors that affect oncology nurse outcomes. METHODS: A secondary analysis of nurse survey data collected in 2006 including 4047 nurses from 282 hospitals in 3 states was performed; t test and χ2 test compared differences between oncology nurses and medical-surgical nurses in nurse outcomes and their assessments of nurse practice environment, as measured by the Practice Environment Scale of the Nursing Work Index. Logistic regression models estimated the effect of nurse practice environment on 4 nurse-reported outcomes: burnout, job dissatisfaction, intention to leave the current position, and perceived quality of care. RESULTS: Oncology nurses reported favorable practice environments and better outcomes than did medical-surgical nurses. All 4 subscales of the Practice Environment Scale of the Nursing Work Index studied were significantly associated with outcomes. Specifically, nurses who reported favorable nursing foundations for quality of care (eg, active in-service or preceptorship programs) were less likely to report burnout and leave their current position. CONCLUSIONS: Better practice environments, including nurse foundations for quality care, can help to achieve optimal nurse outcomes. IMPLICATIONS FOR PRACTICE: Improving hospital practice environments holds significant potential to improve nurse well-being, retention, and quality of care. Specifically, hospitals should consider preceptor programs and continuing education and increase nurses' participation in hospital decision making.

Lower mortality in magnet hospitals.

BACKGROUND: Although there is evidence that hospitals recognized for nursing excellence--Magnet hospitals--are successful in attracting and retaining nurses, it is uncertain whether Magnet recognition is associated with better patient outcomes than non-Magnets, and if so why. OBJECTIVES: To determine whether Magnet hospitals have lower risk-adjusted mortality and failure-to-rescue compared with non-Magnet hospitals, and to determine the most likely explanations. METHOD AND STUDY DESIGN: Analysis of linked patient, nurse, and hospital data on 56 Magnet and 508 non-Magnet hospitals. Logistic regression models were used to estimate differences in the odds of mortality and failure-to-rescue for surgical patients treated in Magnet versus non-Magnet hospitals, and to determine the extent to which differences in outcomes can be explained by nursing after accounting for patient and hospital differences. RESULTS: Magnet hospitals had significantly better work environments and higher proportions of nurses with bachelor's degrees and specialty certification. These nursing factors explained much of the Magnet hospital effect on patient outcomes. However, patients treated in Magnet hospitals had 14% lower odds of mortality (odds ratio 0.86; 95% confidence interval, 0.76-0.98; P=0.02) and 12% lower odds of failure-to-rescue (odds ratio 0.88; 95% confidence interval, 0.77-1.01; P=0.07) while controlling for nursing factors as well as hospital and patient differences. CONCLUSIONS: The lower mortality we find in Magnet hospitals is largely attributable to measured nursing characteristics but there is a mortality advantage above and beyond what we could measure. Magnet recognition identifies existing quality and stimulates further positive organizational behavior that improves patient outcomes.

Nurse staffing, burnout, and health care-associated infection.

BACKGROUND: Each year, nearly 7 million hospitalized patients acquire infections while being treated for other conditions. Nurse staffing has been implicated in the spread of infection within hospitals, yet little evidence is available to explain this association. METHODS: We linked nurse survey data to the Pennsylvania Health Care Cost Containment Council report on hospital infections and the American Hospital Association Annual Survey. We examined urinary tract and surgical site infection, the most prevalent infections reported and those likely to be acquired on any unit within a hospital. Linear regression was used to estimate the effect of nurse and hospital characteristics on health care-associated infections. RESULTS: There was a significant association between patient-to-nurse ratio and urinary tract infection (0.86; P = .02) and surgical site infection (0.93; P = .04). In a multivariate model controlling for patient severity and nurse and hospital characteristics, only nurse burnout remained significantly associated with urinary tract infection (0.82; P = .03) and surgical site infection (1.56; P < .01) infection. Hospitals in which burnout was reduced by 30% had a total of 6,239 fewer infections, for an annual cost saving of up to $68 million. CONCLUSIONS: We provide a plausible explanation for the association between nurse staffing and health care-associated infections. Reducing burnout in registered nurses is a promising strategy to help control infections in acute care facilities.

Impact of nurse staffing mandates on safety-net hospitals: lessons from California.

CONTEXT: California is the first and only state to implement a patient-to-nurse ratio mandate for hospitals. Increasing nurse staffing is an important organizational intervention for improving patient outcomes. Evidence suggests that staffing improved in California hospitals after the mandate was enacted, but the outcome for hospitals bearing a disproportionate share of uncompensated care-safety-net hospitals-remains unclear. One concern was that California's mandate would burden safety-net hospitals without improving staffing or that hospitals would reduce their skill mix, that is, the proportion of registered nurses of all nursing staff. We examined the differential effect of California's staffing mandate on safety-net and non-safety-net hospitals. METHODS: We used a time-series design with Annual Hospital Disclosure data files from the California Office of Statewide Health Planning and Development (OSHPD) for the years 1998 to 2007 to assess differences in the effect of California's mandate on staffing outcomes in safety-net and non-safety-net hospitals. FINDINGS: The mandate resulted in significant staffing improvements, on average nearly a full patient per nurse fewer (-0.98) for all California hospitals. The greatest effect was in those hospitals with the lowest staffing levels at the outset, both safety-net and non-safety-net hospitals, as the legislation intended. The mandate led to significantly improved staffing levels for safety-net hospitals, although there was a small but significant difference in the effect on staffing levels of safety-net and non-safety-net hospitals. Regarding skill mix, a marginally higher proportion of registered nurses was seen in non-safety-net hospitals following the mandate, while the skill mix remained essentially unchanged for safety-net hospitals. The difference between the two groups of hospitals was not significant. CONCLUSIONS: California's mandate improved staffing for all hospitals, including safety-net hospitals. Furthermore, improvement did not come at the cost of a reduced skill mix, as was feared. Alternative and more targeted designs, however, might yield further improvement for safety-net hospitals and reduce potential disparities in the staffing and skill mix of safety-net and non-safety-net hospitals.

Randomized Clinical Trial of the Effectiveness of a Home-Based Advanced Practice Psychiatric Nurse Intervention: Outcomes for Individuals with Serious Mental Illness and HIV.

Individuals with serious mental illness have greater risk for contracting HIV, multiple morbidities, and die 25 years younger than the general population. This high need and high cost subgroup face unique barriers to accessing required health care in the current health care system. The effectiveness of an advanced practice nurse model of care management was assessed in a four-year random controlled trial. Results are reported in this paper. In a four-year random controlled trial, a total of 238 community-dwelling individuals with HIV and serious mental illness (SMI) were randomly assigned to an intervention group (n=128) or to a control group (n=110). Over 12 months, the intervention group received care management from advanced practice psychiatric nurse, and the control group received usual care. The intervention group showed significant improvement in depression (P=.012) and the physical component of health-related quality of life (P=.03) from baseline to 12 months. The advanced practice psychiatric nurse intervention is a model of care that holds promise for a higher quality of care and outcomes for this vulnerable population.