Pulmonary Embolism during a Retrial of Low-dose Clozapine.

Pulmonary emboli (PE) are increasingly recognized as an adverse effect of clozapine. However, little is known about the characteristics or mechanisms of clozapine-associated PE. We present a case of a 34-year-old with treatment-refractory schizophrenia who developed rhabdomyolysis during his first clozapine trial. During re-trial on a lower dose than his initial trial, the patient developed chest pain that he attributed to "pacemakers." The pleuritic description and associated tachycardia prompted medical workup and the patient was ultimately diagnosed with a clozapine-associated PE. The patient's only risk factors for PE were obesity and tobacco use, while his hypercoagulability workup was unrevealing. Clozapine use was continued at a lower dose following these adverse effects given inefficacy of other agents in managing the patient's psychotic symptoms. The patient experienced significant relief of psychotic symptoms with continued clozapine therapy and a course of electroconvulsive therapy. The patient's presentation was unusual in that it occurred during a retrial of clozapine, after the initial trial was stopped when he developed rhabdomyolysis. This case demonstrates the importance of maintaining vigilance for PE in patients on clozapine as well as not dismissing somatic complaints in patients experiencing psychosis. Additionally, given his history rhabdomyolysis, an uncommon adverse effect of clozapine, the development of a second uncommon adverse effect (PE) raises the question of whether these events may be associated.

The 9-Item Patient Health Questionnaire (PHQ-9): an aid to assessment of patient-reported functional outcomes after spinal surgery.

BACKGROUND CONTEXT: Preoperative depression is increasingly understood as an important predictor of patient outcomes after spinal surgery. In this study, we examine the relationship between depression and patient-reported functional outcomes (PRFOs), including disability and pain, at various time points postoperatively. PURPOSE: The objective of this study was to analyze the use of depression, as measured by the 9-Item Patient Health Questionnaire (PHQ-9), as a means of assessing postoperative patient-reported disability and pain. STUDY DESIGN/SETTING: This study includes an analysis of prospective non-randomized spine registry compiled through an academic multispecialty group practice model. PATIENT SAMPLE: A total of 1,000 spinal surgery patients from an affiliated surgical registry, enrolled from January 2010 onward, were included in this study. OUTCOME MEASURES: Pain was assessed via the visual analog scale (VAS) for leg or back pain. Disability was measured by the Oswestry Disability Index (ODI). Depression was measured by the PHQ-9. METHODS: Patient data were collected preoperatively and at 1, 4, 10, and 24 months postoperatively. Data were analyzed via analysis of variance and Pearson correlation coefficient. RESULTS: All patient stratifications analyzed experienced improvements in pain and ability postoperatively, as measured by the VAS and the ODI, respectively. Moderately and severely depressed patients (as measured by preoperative PHQ-9) experienced decreases in the mean PHQ-9 score of -6.00 and -7.96 24 months after surgery, respectively. CONCLUSIONS: In all groups, spinal surgery was followed by relief of pain and improved PRFO. Preoperative depression, as measured by the PHQ-9, predicted postoperative PRFO. Patients with moderate to severe depression as measured by the PHQ-9 experienced large mean decreases in the PHQ-9 score postoperatively. As a psychosocial metric, the PHQ-9 is a useful method of assessing value-added service of a spinal surgery.

Linking Syndemic Stress and Behavioral Indicators of Main Partner HIV Transmission Risk in Gay Male Couples.

The purpose of the current study was to examine whether syndemic stress in partnered gay men might undermine communication processes essential to the utilization of negotiated safety and other harm reduction strategies that rely on partners' HIV status disclosure. Participants included 100 gay male couples (N = 200 individuals) living in the U.S., who responded to an online survey. Participants completed measures of five syndemic factors (depression, poly-drug use, childhood sexual abuse, intimate partner violence, and sexual compulsivity). They also reported on whether condoms were used during first intercourse together and the timing of first condomless anal intercourse (CAI) relative to HIV disclosure in their relationship. Results of binary logistic regression analyses supported the hypothesis that the sum of partners' syndemic stress was negatively associated with condom use at first intercourse and with HIV disclosure prior to first CAI. Syndemic stress may contribute to HIV transmission risk between main partners in part because it accelerates the progression to CAI and interferes with communication processes central to harm reduction strategies utilized by gay men in relationships. Implications for prevention strategies and couples interventions, such as couples HIV counseling and testing, that facilitate communication skill-building, are discussed.

The role of sexual expectancies of substance use as a mediator between adult attachment and drug use among gay and bisexual men.

BACKGROUND: Research exploring substance use in gay and bisexual men has increasingly paid attention to interpersonal dynamics and relational concerns associated with the use of substances. The current study explored the role of adult attachment style on drug use as well as the potential mediating role of sexual expectancies of substance use among gay and bisexual men. METHODS: Online survey data were gathered from 122 gay and bisexual men across the U.S., with a mean age of 33 years. All participants were HIV-negative and identified their relationship status as single. Survey measures included attachment style, sexual expectancies of substance use, and recent drug use. RESULTS: While neither anxious or avoidant attachment were directly associated with the odds of recent drug use, they were positively associated with sexual expectancies of substance use (ß=0.27, p<0.01, and ß=0.21, p<0.05) which, in turn, were positively associated with the odds of drug use (expB=1.09, p<0.01). Bootstrapping tests of indirect effects revealed a significant indirect relationship between anxious attachment and drug use through sexual expectancies of substance use (ß=0.11, p<0.05), but not for avoidant attachment. CONCLUSIONS: This study highlights the importance of interpersonal expectancies as motivators for drug use among gay and bisexual men. Sexual expectancies of substance use were associated with drug use and anxious adult attachment was associated indirectly with drug use through these sexual expectancies.

Major differences between tumor and normal human cell fates after exposure to chemotherapeutic monofunctional alkylator.

The major dilemma of cancer chemotherapy has always been a double-edged sword, producing resistance in tumor cells and life-threatening destruction of nontumorigenic tissue. Glioblastoma is the most common form of primary brain tumor, with median survival at 14 months after surgery, radiation and temozolomide (monofunctional alkylator) therapy. Treatment failure is most often due to temozolomide-resistant tumor growth. The underlying basis for development of tumor cell resistance to temozolomide instead of death is not understood. Our current results demonstrate that both cervical carcinoma (HeLa MR) and glioblastoma (U251) tumor cells exposed to an equivalent chemotherapeutic concentration of a monofunctional alkylator undergo multiple cell cycles, maintenance of metabolic activity, and a prolonged time to death that involves accumulation of Apoptosis Inducing Factor (AIF) within the nucleus. A minority of the tumor cell population undergoes senescence, with minimal caspase cleavage. Surviving tumor cells are comprised of a very small subpopulation of individual cells that eventually resume proliferation, out of which resistant cells emerge. In contrast, normal human cells (MCF12A) exposed to a monofunctional alkylator undergo an immediate decrease in metabolic activity and subsequent senescence. A minority of the normal cell population undergoes cell death by the caspase cleavage pathway. All cytotoxic events occur within the first cell cycle in nontumorigenic cells. In summation, we have demonstrated that two different highly malignant tumor cell lines slowly undergo very altered cellular and temporal responses to chemotherapeutic monofunctional alkylation, as compared to rapid responses of normal cells. In the clinic, this produces resistance and growth of tumor cells, cytotoxicity of normal cells, and death of the patient.