Telehealth-Based Music Therapy Versus Cognitive Behavioral Therapy for Anxiety in Cancer Survivors: Rationale and Protocol for a Comparative Effectiveness Trial.

BACKGROUND: Cancer survivors represent one of the fastest growing populations in the United States. Unfortunately, nearly 1 in 3 survivors experience anxiety symptoms as a long-term consequence of cancer and its treatment. Characterized by restlessness, muscle tension, and worry, anxiety worsens the quality of life; impairs daily functioning; and is associated with poor sleep, depressed mood, and fatigue. Although pharmacological treatment options are available, polypharmacy has become a growing concern for cancer survivors. Music therapy (MT) and cognitive behavioral therapy (CBT) are evidence-based, nonpharmacological treatments that have demonstrated effectiveness in treating anxiety symptoms in cancer populations and can be adapted for remote delivery to increase access to mental health treatments. However, the comparative effectiveness of these 2 interventions delivered via telehealth is unknown. OBJECTIVE: The aims of the Music Therapy Versus Cognitive Behavioral Therapy for Cancer-related Anxiety (MELODY) study are to determine the comparative effectiveness of telehealth-based MT versus telehealth-based CBT for anxiety and comorbid symptoms in cancer survivors and to identify patient-level factors associated with greater anxiety symptom reduction for MT and CBT. METHODS: The MELODY study is a 2-arm, parallel-group randomized clinical trial that aims to compare the effectiveness of MT versus CBT for anxiety and comorbid symptoms. The trial will enroll 300 English- or Spanish-speaking survivors of any cancer type or stage who have experienced anxiety symptoms for at least 1 month. Participants will receive 7 weekly sessions of MT or CBT delivered remotely via Zoom (Zoom Video Communications, Inc) over 7 weeks. Validated instruments to assess anxiety (primary outcome), comorbid symptoms (fatigue, depression, insomnia, pain, and cognitive dysfunction), and health-related quality of life will be administered at baseline and at weeks 4, 8 (end of treatment), 16, and 26. Semistructured interviews will be conducted at week 8 with a subsample of 60 participants (30 per treatment arm) to understand individual experiences with the treatment sessions and their impact. RESULTS: The first study participant was enrolled in February 2022. As of January 2023, 151 participants have been enrolled. The trial is expected to be completed by September 2024. CONCLUSIONS: This study is the first and largest randomized clinical trial to compare the short- and long-term effectiveness of remotely delivered MT and CBT for anxiety in cancer survivors. Limitations include the lack of usual care or placebo control groups and the lack of formal diagnostic assessments for psychiatric disorders among trial participants. The study findings will help guide treatment decisions for 2 evidence-based, scalable, and accessible interventions to promote mental well-being during cancer survivorship. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46281.

Depression as a risk factor for cancer: from pathophysiological advances to treatment implications.

Innate immune activation and inflammation have been posited to play a role in the pathophysiology of both depression and neoplastic growth. Cancer patients experience a threefold higher rate of depression than the general population within the first five years of diagnosis. Chronic depression is associated with increased cancer risk and shortened survival. Although the precise cellular and molecular mechanisms of this bidirectional relationship remain unclear, elevated concentrations of circulating plasma proinflammatory cytokines associated with depression may mediate the neuroendocrine, neural, and immune pathways that account for the relationship. Proinflammatory cytokines, in turn, are known to modulate key neurobiological correlates of depression including hypothalamic-pituitary-adrenal (HPA) axis dysregulation, monoamine neurotransmitter metabolism, and limbic system activity. Research is needed to determine whether optimal depression treatment improves cancer survival and to develop antidepressant strategies that target molecular and cellular mechanisms mediating inflammation and the neurobiological pathways influenced by the proinflammatory cytokines.

Expression of HSV-1 receptors in EBV-associated lymphoproliferative disease determines susceptibility to oncolytic HSV.

Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disease (LPD) after hematopoietic stem cell or solid organ transplantation remains a life-threatening complication. Expression of the virus-encoded gene product, EBER, has been shown to prevent apoptosis via blockade of PKR activation. As PKR is a major cellular defense against Herpes simplex virus (HSV), and oncolytic HSV-1 (oHSV) mutants have shown promising antitumor efficacy in preclinical models, we sought to determine whether EBV-LPD cells are susceptible to infection by oHSVs. We tested three primary EBV-infected lymphocyte cell cultures from neuroblastoma (NB) patients as models of naturally acquired EBV-LPD. NB12 was the most susceptible, NB122R was intermediate and NB88R2 was essentially resistant. Despite EBER expression, PKR was activated by oHSV infection. Susceptibility to oHSV correlated with the expression of the HSV receptor, nectin-1. The resistance of NB88R2 was reversed by exogenous nectin-1 expression, whereas downregulation of nectin-1 on NB12 decreased viral entry. Xenografts derived from the EBV-LPDs exhibited only mild (NB12) or no (NB88R2) response to oHSV injection, compared with a NB cell line that showed a significant response. We conclude that EBV-LPDs are relatively resistant to oHSV virotherapy, in some cases, due to low virus receptor expression but also due to intact antiviral PKR signaling.

Cancer and post-traumatic stress disorder: diagnosis, pathogenesis and treatment considerations.

OBJECTIVE: The purpose of this article was to review the literature regarding diagnosis, pathogenesis, and treatment of post-traumatic stress disorder (PTSD) associated with cancer. METHOD: We surveyed studies examining the validity of diagnostic scales commonly used to measure PTSD in patients with cancer. Neurobiological underpinnings of PTSD and cancer, including inflammation as the physiological mechanism linking these comorbidities, were examined. Psychopharmacologic and psychotherapeutic treatment of PTSD symptoms in patients with cancer was reviewed. In addition, potential drug-drug interactions between psychotropic medications commonly used to treat PTSD and anti-cancer agents were reviewed. RESULTS: Multiple studies demonstrated the validity of the PTSD Checklist Civilian Version (PCL-C) in diagnosing PTSD in patients with cancer. Research has shown that PTSD as defined in DSM-IV appears to be a better model for conceptualizing distress in patients with cancer than a generalized "distress" model. Epidemiologic studies have shown an increased incidence of PTSD associated with cancer; however, literature regarding characteristics of PTSD in patients with cancer is cross-sectional in nature. SIGNIFICANCE OF RESULTS: Future research focusing on longitudinal, prospective studies to identify patients at risk, determine causal or aggravating factors, and develop preventive interventions is needed. Further study of PTSD in patients with cancer may help increase recognition of this disorder, optimize treatment, and enhance the quality of life of these individuals.

VEGF blockade decreases the tumor uptake of systemic oncolytic herpes virus but enhances therapeutic efficacy when given after virotherapy.

Effective therapies for metastatic sarcomas remain elusive. Oncolytic viruses have shown promise as anticancer agents, but their access to metastatic sites following systemic delivery is low. As systemic delivery of small-molecule chemotherapy is enhanced by previous treatment with antiangiogenic agents because of changes in intravascular-to-tumor interstitial pressure, we sought to determine whether antiangiogenic pretreatment increases the antitumor efficacy of systemic virotherapy by increasing virus uptake into tumor. Virus biodistribution and antitumor effects were monitored in tumor-bearing mice given antihuman vascular endothelial growth factor (VEGF) or antimouse VEGFR2 before or after an intravenous (i.v.) injection of virus. Without pretreatment, the average virus titers in the tumor samples amplified 1700-fold over 48 h but were undetectable in other organs. After antiangiogenic treatment, average virus titers in the tumor samples were unchanged or in some cases decreased up to 100-fold. Thus, antiangiogenic pretreatment failed to improve the tumor uptake of systemic oncolytic herpes simplex virus (oHSV), in contrast to previously reported enhanced uptake of small molecules. Superior tumor control because of the combined effects of virus and anti-VEGF was seen most dramatically when anti-VEGF was given after virus. Our data suggest that i.v. oHSV can treat distant sites of disease and can be enhanced by antiangiogenic therapy, but only when given in the proper sequence.

Evaluation of soluble CD30 as an immunologic marker in heart transplant recipients.

CD30 is an immunologic molecule that belongs to the TNF-R superfamily. CD30 serves as a T-cell signal transducing molecule that is expressed by a subset of activated T lymphocytes, CD45RO+ memory T cells. Augmentation of soluble CD30 during kidney transplant rejection has been reported. Our study sought to determine whether the level of sCD30 prior to heart transplant could categorize patients into high versus low immunologic risk for a poor outcome. A significant correlation was observed between high levels of soluble CD30 and a reduced incidence of infection. None of the 35 patients with high pretransplant levels of sCD30 level (>90 U/mL) developed infections posttransplantation. However, 9 of 65 patients who had low levels of sCD30 (<90 U/mL) developed infections posttransplantation (P < .02). No remarkable differences were noted among the other clinical parameters. The results also showed that the high-definition flow-bead (HDB) assay detected both weak and strong class I and class II HLA antibodies, some of which (weak class II HLA Abs) were undetectable by the anti-human globulin cytotoxicity method. In addition, more antibody specificities were detected by HDB. In conclusion, we have observed that high levels of sCD30 prior to heart transplant may be associated with greater immunologic ability and therefore produce a protective effect on the development of infection post heart transplant. We have also shown that the HDB assay is superior to the visual cytotoxicity method to detect HLA antibodies, especially those to class II HLA antigens.

The relation between body fat distribution and cardiovascular risk factors in patients with schizophrenia: a cross-sectional pilot study.

BACKGROUND: Obesity has recently become a concern for physicians treating schizophrenic patients. Obesity is associated with hypertension, dyslipidemia, and diabetes mellitus. In this pilot study, we investigate which anthropometric measurement, body mass index or waist circumference, is a better predictor of cardiovascular risk factors in patients with schizophrenia. METHOD: This cross-sectional study, conducted from January 2001 to January 2002, examined body fat distribution and its relation to cardiovascular risk factors in 62 patients with schizophrenia (DSM-IV) recruited from an outpatient psychiatric clinic. RESULTS: Chi-square analysis revealed that an increased waist circumference was associated with dyslipidemia (p < .01), hypertension (p < .05), and abnormal serum glucose (p < .05), whereas an increased body mass index was only associated with dyslipidemia (p < .05). In logistic regression analysis, after controlling for age, gender, race, ethnicity, smoking, and body mass index, increased waist circumference remained significantly associated with dyslipidemia (odds ratio = 2.08, 95% CI = 1.01 to 1.15, p < .05) and hypertension (odds ratio = 2.05, 95% CI = 1.02 to 1.17, p < .05). CONCLUSIONS: Waist circumference revealed a stronger correlation than body mass index to cardiovascular risk factors in patients with schizophrenia. We propose the measurement of waist circumference as a screening tool for cardiovascular risk factors in this population. Waist circumference measurement can provide an opportunity for primary prevention of coronary heart disease and diabetes mellitus in patients with schizophrenia.

Prevalence of Metabolic Syndrome in Hispanic and Non-Hispanic Patients With Schizophrenia.

BACKGROUND: Metabolic syndrome, a constellation of truncal obesity, dyslipidemia, disturbed insulin and glucose metabolism, and hypertension, is associated with the development of diabetes mellitus and coronary heart disease. However, the prevalence of metabolic syndrome in Hispanic patients with schizophrenia and whether they differ from comparable non-Hispanic patients is uncertain. METHOD: This cross-sectional study, conducted from January 2002 to May 2002, included 48 patients with schizophrenia who were recruited from an outpatient psychiatric clinic. Metabolic syndrome was defined using the criteria of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. RESULTS: The prevalence of metabolic syndrome was 63% in all patients with schizophrenia. The metabolic syndrome was present in 41% of non-Hispanic patients and in 74% of Hispanic patients with schizophrenia. Metabolic syndrome was present in 70% of Cuban Americans and 88% of other Hispanic subgroups with schizophrenia. Metabolic syndrome was associated with waist circumference (p <.05) and high-density lipoprotein cholesterol (p <.05) in logistic regression analysis. CONCLUSIONS: These data suggest that schizophrenic patients have a 3-fold greater risk to develop metabolic syndrome than the general population. Hispanic schizophrenic patients have a significantly greater prevalence of metabolic syndrome than non-Hispanic schizophrenic patients (p <.05). An increased waist circumference is the strongest clinical correlate with metabolic syndrome in schizophrenic patients.

Citalopram treatment of major depressive disorder in Hispanic HIV and AIDS patients: a prospective study.

Fourteen Hispanic and six non-Hispanic outpatients with HIV-spectrum illness and major depressive disorder were enrolled in a 6-week, open-label, flexible-dose study of citalopram (dose range=10-40 mg/day). The depressive symptoms of 50% of the 14 patients who completed the study responded to citalopram (mean dose=34 mg/day). The treatment response rate, effective citalopram dose, total number of reported adverse events, and attrition rate did not differ between the ethnic groups. Two patients discontinued because of adverse events (rash, nausea), and four patients discontinued because of noncompliance with the protocol. The findings suggest that citalopram is an effective and well-tolerated antidepressant for Hispanic and non-Hispanic HIV-infected patients.

Salmonella enterica serotype Javiana infections associated with amphibian contact, Mississippi, 2001.

Salmonella Javiana is a Salmonella serotype that is restricted geographically in the United States to the Southeast. During the summer of 2001, the number of reported S. Javiana infections in Mississippi increased sevenfold. To identify sources of infection, we conducted a case-control study, defining a case as an infection with S. Javiana between August and September in a Mississippi resident. We enrolled 55 cases and 109 controls. Thirty (55%) case patients reported exposure to amphibians, defined as owning, touching, or seeing an amphibian on one's property, compared with 30 (29%) controls (matched odds ratio 2.8, P=0.006). Contact with amphibians and their environments may be a risk factor for human infection with S. Javiana. The geographic pattern of S. Javiana infections in the United States mimics the distribution of certain amphibian species in the Southeast. Public health officials should consider amphibians as potential sources of salmonellosis, and promote hand washing after contact with amphibians.

A prospective trial of sustained-release bupropion for depression in HIV-seropositive and AIDS patients.

To date, the authors know of no prospective studies of sustained-release bupropion in depressed HIV-seropositive patients. The purpose of this study was to evaluate the efficacy and tolerability of sustained-release bupropion in 20 depressed HIV-positive adult outpatients. Twenty outpatients with HIV spectrum illness, a DSM-IV-diagnosed major depressive disorder confirmed with the Structured Clinical Interview for DSM-IV, and Mini-Mental State Examination scores >20 were recruited into a 6-week, open-label, flexible-dose study of sustained-release bupropion (100-300 mg/day). Twelve patients (60%) responded to sustained-release bupropion at a mean dose of 265 mg/day. Five patients (25%) discontinued study participation secondary to adverse events. Preliminary findings suggest that sustained-release bupropion is effective for the treatment of depression in HIV-positive patients, regardless of HIV clinical staging. Furthermore, it appears to be well tolerated in patients with AIDS-related medical conditions.

Rural v. urban aspects of cancer: first-year data from the Mississippi Central Cancer Registry.

This study investigated various aspects of cancer between rural and urban localities. The Mississippi State Department of Health Central Cancer Registry received reports of 9,685 new cancer cases in 1996 while there were 5,732 cancer deaths. Even though no difference was found between rural and urban age-adjusted cancer incidence (and mortality), for the vast majority of results, there was a significant difference between rural and urban residents for stage of disease at initial diagnosis. Results also show that the proportion of tumors unstaged at diagnosis is greater for rural compared to urban residents. While this study has limitations, findings suggest that rural residents in Mississippi and rural African American women in particular, have less access to, or utilization of, early cancer detection programs and/or quality medical care.

Fiber knob modifications overcome low, heterogeneous expression of the coxsackievirus-adenovirus receptor that limits adenovirus gene transfer and oncolysis for human rhabdomyosarcoma cells.

Exploiting the lytic life cycle of viruses has gained recent attention as an anticancer strategy (oncolysis). To explore the utility of adenovirus (Ad)-mediated oncolysis for rhabdomyosarcoma (RMS), we tested RMS cell lines for Ad gene transduction and infection. RMS cells were variably transduced by Ad. Compared with control cells, RMS cells were less sensitive or even resistant to oncolysis by wild-type virus. RMS cells expressed the Ad internalization receptors, alpha(v) integrins, but had low or undetectable expression of the major attachment receptor, coxsackievirus-Ad receptor (CAR). Mutant Ads with ablated CAR binding exhibited only 5-20% of transgene expression in RMS cells seen with a wild-type vector, suggesting that residual or heterogeneous CAR expression mediated the little transduction that was detectable. Immunohistochemical analysis of archived clinical specimens showed little detectable CAR expression in five embryonal and eight alveolar RMS tumors. Stable transduction of the cDNA for CAR enabled both efficient Ad gene transfer and oncolysis for otherwise resistant RMS cells, suggesting that poor CAR expression is the limiting feature. Gene transfer to RMS cells was increased >2 logs using Ads engineered with modified fiber knobs containing either an integrin-binding RGD peptide or a polylysine peptide in the exposed HI loop. The RGD modification enabled increased oncolysis for RMS cells by a conditionally replicative Ad, Ad delta24RGD, harboring a retinoblastoma-binding mutation in the E1A gene. Thus, the development of replication-competent vectors targeted to cell surface receptors other than CAR is critical to advance the use of Ad for treating RMS.

Spinal cord injury in Mississippi. Findings and evaluation, 1992-1994.

STUDY DESIGN: The Mississippi spinal cord injury surveillance system is both active and passive, designed to capture all cases of spinal cord injury through mandated reporting by multiple sources. Each case is confirmed by medical record review. OBJECTIVES: To describe the development of a state-wide spinal cord injury surveillance system, discuss findings from the system, and evaluate sensitivity. SUMMARY OF BACKGROUND DATA: In the United States, the annual incidence rate of spinal cord injury requiring hospital admission has been estimated at 32-50 per million. With prehospital fatalities included, the estimated incidence rate ranges from 43 to 55 per million population annually. METHODS: In the current study all cases identified during the first 2 years of operation of the spinal cord injury (SCI) system were included. To evaluate the sensitivity of the system, International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes from each hospital's discharge database were used. RESULTS: The incidence rate among patients in hospitals and prehospital fatal cases was 77 per million. The rate for patients in hospitals was 59 per million. The incidence rate of spinal cord injury among males was 4.4 times higher than among females. Rates of spinal cord injury were highest among persons 20-24 years of age. Rates were similar for whites and blacks. The most frequent causes of spinal cord injury were motor vehicle collisions, violence, and falls. Additional cases were identified during the evaluation, resulting in a 94% sensitivity. CONCLUSIONS: Mississippi's spinal cord injury incidence rates are substantially higher than rates reported for other states except Alaska. The surveillance system was found to be very complete. Prevention efforts should focus on increasing safety belt usage, increasing alcohol awareness, and reducing violence.

The impact of zidovudine use in HIV-infected pregnant women on vertical transmission of HIV in Mississippi.

In February 1994, results of a large placebo-controlled trial of zidovudine (ZDV) use during pregnancy (ACTG 076) showed a dramatic reduction in vertical transmission of HIV. In August 1994, the Public Health Service (PHS) recommended routine ZDV use in HIV infected pregnant women and their neonates for the prevention of vertical transmission. We retrospectively reviewed vertical transmission rates of HIV in Mississippi from 1/1/90 to 8/30/94 before the PHS guidelines were released and from 9/1/94 to 12/31/97 after the PHS guidelines were released. We also reviewed data on ZDV use in HIV infected pregnant women and their neonates from 9/1/94 to 12/31/97. Antenatal, intrapartum and neonatal ZDV use increased from 61%, 59% and 73% respectively to 79%, 77% and 92% respectively. After 9/1/94, vertical transmission rates fell by 44%. Zidovudine use during pregnancy has increased in Mississippi since release of the PHS guidelines resulting in a dramatic decline in vertical transmission rates.

An investigation of genital ulcers in Jackson, Mississippi, with use of a multiplex polymerase chain reaction assay: high prevalence of chancroid and human immunodeficiency virus infection.

In 1994, an apparent outbreak of atypical genital ulcers was noted by clinicians at the sexually transmitted disease clinic in Jackson, Mississippi. Of 143 patients with ulcers tested with a multiplex polymerase chain reaction (PCR) assay, 56 (39%) were positive for Haemophilus ducreyi, 44 (31%) for herpes simplex virus, and 27 (19%) for Treponema pallidum; 12 (8%) were positive for > 1 organism. Of 136 patients tested for human immunodeficiency virus (HIV) by serology, 14 (10%) were HIV-seropositive, compared with none of 200 patients without ulcers (P < .001). HIV-1 DNA was detected by PCR in ulcers of 6 (50%) of 12 HIV-positive patients. Multivariate analysis indicated that men with chancroid were significantly more likely than male patients without ulcers to report sex with a crack cocaine user, exchange of money or drugs for sex, and multiple sex partners. The strong association between genital ulcers and HIV infection in this population highlights the urgency of preventing genital ulcers in the southern United States.

Spinal cord injury incidence in Mississippi: a capture-recapture approach.

BACKGROUND: Many studies have investigated spinal cord injury incidence rates. Few, however, have adjusted for the underascertainment. The current study used the capture-recapture method to estimate the ascertainment-corrected spinal cord injury incidence rate in Mississippi. METHODS: Two sources were used for case ascertainment: Mississippi's spinal cord injury registry and hospital reports. The two-sample capture-recapture method was used to adjust for undercount. RESULTS: Two hundred one spinal cord injuries were reported to or found by the Mississippi State Department of Health in 1993, with a crude incidence rate of 7.8 per 100,000 population per year among hospital admissions and prehospital fatalities. Using the two-sample capture-recapture method, it is estimated that the incidence rate would be 9.3 per 100,000 population per year. CONCLUSION: Capture-recapture estimates suggest that Mississippi's spinal cord injury incidence rate is more than twice the national average.

Endemic blastomycosis in Mississippi: epidemiological and clinical studies.

In order to clarify the epidemiology and clinical spectrum of endemic blastomycosis, we reviewed the charts of 326 culture and/or histologically proven cases of blastomycosis in Mississippi from 1979 to 1988. Cases were dispersed throughout the state, but counties in central and south-central Mississippi reported 63% of all blastomycosis cases. The average annual incidence rate was 1.3 cases per 100,000 population. The majority of cases were in men (male to female ratio 1.7:1), and most patients were aged in their third through seventh decades (82%). Outdoor occupations were noted for only 28.9% of cases. Cases occurred throughout the year with no significant seasonal peak. Although 55% saw a physician within 7 days of onset of illness, 29% presented after 1 month. Despite early presentation, diagnosis was often delayed for more than 1 month (43.3%). Single organs were involved in 82.8% of cases. For all cases, organ systems involved included lungs (91.4%), skin (18.1%), bone (4.3%), genitourinary system (1.8%), and central nervous system (1.2%). The presence of skin or bone disease was associated with multiorgan involvement. Thirty-three patients died (11.5%), 6 of whom received no therapy. Patients who died were significantly older than those who survived. A successful outcome without relapse was noted in 86.5% of amphotericin B-treated patients and in 81.7% of ketoconazole-treated patients. The relapse rate for ketoconazole-treated patients was higher than for amphotericin B-treated patients (14% and 3.9% respectively).