Diet-Related and Gut-Derived Metabolites and Health Outcomes: A Scoping Review.

We conducted a scoping review to map available evidence about the health impact of gut microbiota-derived metabolites. We searched PubMed and Embase for studies that assessed the health impact of ten metabolites on any health condition: deoxycholate or deoxycholic acid (DCA), lithocholate or lithocholic acid (LCA), glycolithocholate or glycolithocholic acid, glycodeoxycholate or glycodeoxycholic acid, tryptamine, putrescine, d-alanine, urolithins, N-acetylmannosamine, and phenylacetylglutamine. We identified 352 eligible studies with 168,072 participants. Most (326, 92.6%) were case-control studies, followed by cohort studies (14, 4.0%), clinical trials (8, 2.3%), and cross-sectional studies (6, 1.7%). Most studies assessed the following associations: DCA on hepatobiliary disorders (64 studies, 7976 participants), colorectal cancer (19 studies, 7461 participants), and other digestive disorders (27 studies, 2463 participants); LCA on hepatobiliary disorders (34 studies, 4297 participants), colorectal cancers (14 studies, 4955 participants), and other digestive disorders (26 studies, 2117 participants); putrescine on colorectal cancers (16 studies, 94,399 participants) and cancers excluding colorectal and hepatobiliary cancers (42 studies, 4250 participants). There is a need to conduct more prospective studies, including clinical trials. Moreover, we identified metabolites and conditions for which systemic reviews are warranted to characterize the direction and magnitude of metabolite-disease associations.

Should Physicians Disclose Their Own Health Challenges? Perspectives of Patients With Chronic Pain.

This study explores how patients with chronic pain view the impact of physician self-disclosure on the patient-physician relationship. We conducted mixed-methods analyses of a cross-sectional survey eliciting experiences and attitudes regarding physician self-disclosure among 934 adults with self-reported chronic pain. Patients with chronic pain commonly recalled experiences of physician self-disclosure, most often "small talk" or physicians' disclosure of their own chronic pain. Patients generally rated these experiences to be beneficial. Patients frequently said they would benefit from seeing a physician who has had chronic pain, or that they would want their physician to self-disclose their own chronic pain. Those who had never experienced self-disclosure were more likely to want their physician to self-disclose their own chronic pain. Nonetheless, patients held varying perspectives toward the advantages and disadvantages of physician self-disclosure, believing that self-disclosure could either positively or negatively impact the patient-physician relationship and care and communication.

Pancreatic Pain-Knowledge Gaps and Research Opportunities in Children and Adults: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

ABSTRACT: A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to focus on research gaps and opportunities in pancreatic pain. The event was held on July 21, 2021, and structured into 4 sessions: (1) pathophysiology; (2) biomarkers, mediators, and pharmacology of pain; (3) pain assessment; and (4) pain treatment challenges and opportunities. The current state of knowledge was reviewed; many knowledge gaps and research needs were identified that require further investigation. Common themes included the need to better understand the underlying mechanisms of pain in pancreatic diseases, the relationship of visceral neural pathways and central pain centers, the role of behavioral factors and disorders on the perception of pain, and differences in pain perception and processes in children when compared with adults. In addition, the role of genetic risk factors for pain and the mechanisms and role of placebos in pain treatment were discussed. Methods of pain assessment including quantitative sensory testing were examined, as well as the process of central sensitization of pain. Finally, newer approaches to pain management including cognitive behavioral therapy, nerve stimulation, experimental (nonopioid) drugs, and cannabinoid compounds were covered.

Inflammation and Risk of Depression in HIV: Prospective Findings From the Multicenter AIDS Cohort Study.

Studies suggest that inflammation might be involved in the pathogenesis of depression. Individuals with human immunodeficiency virus (HIV) have a higher risk of depression and elevated inflammatory profiles. Despite this, research on the link between inflammation and depression among this high-risk population is limited. We examined a sample of men who have sex with men from the Multicenter AIDS Cohort Study in prospective analyses of the association between inflammation and clinically relevant depression symptoms, defined as scores >20 on Center for Epidemiological Studies Depression Scale. We included 1,727 participants who contributed 9,287 person-visits from 1984 to 2010 (8,218 with HIV (HIV+) and 1,069 without (HIV-)). Exploratory factor analysis (EFA) was used to characterize underlying inflammatory processes from 19 immune markers. Logistic regression with generalized estimating equations was used to evaluate associations between inflammatory processes and depressive symptoms stratified by HIV serostatus. Three EFA-identified inflammatory processes (EIPs) were identified. EIP-1 scores-described by soluble tumor necrosis factor receptor 2 (sTNF-R2), soluble interleukin-2 receptor α (sIL-2Rα), sCD27, B-cell activating factor, interferon γ-induced protein 10 (IP-10), soluble interleukin-6 receptor (sIL-6R), sCD14, and sGP130-were significantly associated with 9% higher odds of depressive symptoms in HIV+ participants (odds ratio = 1.09; 95% confidence interval: 1.03, 1.16) and 33% higher odds in HIV- participants (odds ratio = 1.33; 95% confidence interval: 1.09, 1.61). Findings suggest that immune activation might be involved in depression risk among both HIV+ and HIV- men who have sex with men.

Optimal metrics for identifying long term patterns of depression in older HIV-infected and HIV-uninfected men who have sex with men.

OBJECTIVES: Center of Epidemiologic Studies-Depression Scale (CES-D) provides a snapshot of symptom severity at a single point in time. However, the best way of using CES-D to classify long-term depression is unclear. METHOD: To identify long-term depression among HIV-infected and HIV-uninfected 50+ year-old men who have sex with men (MSM) with at least 5 years of follow-up, we compared sensitivities and specificities of CES-D-based metrics (baseline CES-D; four consecutive CES-Ds; group-based trajectory models) thresholded at 16 and 20 to a clinician's evaluation of depression phenotype based on all available data including CES-D history, depression treatment history, drug use history, HIV disease factors, and demographic characteristics. RESULTS: A positive depressive phenotype prevalence was common among HIV-infected (prevalence = 33.1%) and HIV-uninfected MSM (prevalence = 23.2%). Compared to the depressive phenotype, trajectory models of CES-D≥20 provided highest specificities among HIV-infected (specificity = 99.9%, 95% Confidence Interval [CI]:99.4%-100.0%) and HIV-uninfected MSM (specificity = 99.0%, 95% CI:97.4%-99.7%). Highest sensitivities resulted from classifying baseline CES-D ≥ 16 among HIV-infected MSM (sensitivity = 75.0%, 95% CI:67.3%-81.7%) and four consecutive CES-Ds ≥ 16 among HIV-uninfected MSM (sensitivity = 81.0%, 95% CI:73.7%-87.0%). CONCLUSION: Choice of method should vary, depending on importance of false positive or negative rate for long-term depression in HIV-infected and HIV-uninfected MSM.

Association of long-term patterns of depressive symptoms and attention/executive function among older men with and without human immunodeficiency virus.

Older HIV-infected men are at higher risk for both depression and cognitive impairments, compared to HIV-uninfected men. We evaluated the association between longitudinal patterns of depressive symptoms and attention/executive function in HIV-infected and HIV-uninfected men aged 50+ years to understand whether HIV infection influenced the long-term effect of depression on attention/executive function. Responses to the Center for Epidemiologic Studies-Depression scale and attention/executive function tests (Trail Making Test Part B and Symbol Digit Modalities Test) were collected semiannually from May 1986 to April 2015 in 1611 men. Group-based trajectory models, stratified by HIV status, were used to identify latent patterns of depressive symptoms and attention/executive function across 12 years of follow-up. We identified three depression patterns for HIV-infected and HIV-uninfected men (rare/never 50.0 vs. 60.6%, periodically depressed 29.6 vs. 24.5%, chronic high 20.5 vs.15.0%, respectively) and three patterns of attention/executive function for HIV-infected and HIV-uninfected men (worst-performing 47.4 vs. 45.1%; average 41.9 vs. 47.0%; best-performing 10.7 vs. 8.0%, respectively). Multivariable logistic regression models were used to assess associations between depression patterns and worst-performing attention/executive function. Among HIV-uninfected men, those in the periodically depressed and chronic high depressed groups had higher odds of membership in the worst-performing attention/executive function group (adjusted odds ratio [AOR] = 1.45, 95% CI 1.04, 2.03; AOR = 2.25, 95% CI 1.49, 3.39, respectively). Among HIV-infected men, patterns of depression symptoms were not associated with patterns of attention/executive function. Results suggest that HIV-uninfected, but not HIV-infected, men with chronic high depression are more likely to experience a long-term pattern of attention/executive dysfunction.

Neuropsychiatric Effects of HIV Antiviral Medications.

The development of antiretroviral therapy (ART) has dramatically increased the lifespan of HIV patients but treatment is complicated by numerous adverse effects and toxicities. ART complications include neuropsychiatric, metabolic, gastrointestinal, cardiac, and numerous other toxicities, and clinicians often have to choose one toxicity over another to offer the best medication regimen for a patient. Some antiviral drugs cause significant neuropsychiatric complications, including depression, cognitive impairment, and sleep disturbance. Even in careful studies, it may be difficult to determine which effects are related to the virus, the immune system, or the treatment. Of the six currently marketed classes of antiviral drugs, the nucleoside reverse transcriptase inhibitors and the non-nucleoside reverse transcriptase inhibitors have been most commonly associated with neuropsychiatric complications. Within these classes, certain drugs are more likely to cause difficulty than others. We review the contention regarding the central nervous system (CNS) complications of efavirenz, as well as debate about the role of CNS penetration in drug effectiveness and toxicity. A thorough working knowledge of the neuropsychiatric consequences of ART allows clinicians to tailor treatment more successfully to individual patients as well as to identify ART more quickly as the source of a problem or symptom.

Perspectives on the Use of eHealth in the Management of Patients With Schizophrenia.

Mobile devices, digital technologies, and web-based applications-known collectively as eHealth (electronic health)-could improve health care delivery for costly, chronic diseases such as schizophrenia. Pharmacologic and psychosocial therapies represent the primary treatment for individuals with schizophrenia; however, extensive resources are required to support adherence, facilitate continuity of care, and prevent relapse and its sequelae. This paper addresses the use of eHealth in the management of schizophrenia based on a roundtable discussion with a panel of experts, which included psychiatrists, a medical technology innovator, a mental health advocate, a family caregiver, a health policy maker, and a third-party payor. The expert panel discussed the uses, benefits, and limitations of emerging eHealth with the capability to integrate care and extend service accessibility, monitor patient status in real time, enhance medication adherence, and empower patients to take a more active role in managing their disease. In summary, to support this technological future, eHealth requires significant research regarding implementation, patient barriers, policy, and funding.

Persistent CSF but not plasma HIV RNA is associated with increased risk of new-onset moderate-to-severe depressive symptoms; a prospective cohort study.

Major depressive disorder is the most common neuropsychiatric complication in human immunodeficiency virus (HIV) infections and is associated with worse clinical outcomes. We determined if detectable cerebrospinal fluid (CSF) HIV ribonucleic acid (RNA) at threshold ≥50 copies/ml is associated with increased risk of depression. The CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort is a six-center US-based prospective cohort with bi-annual follow-up of 674 participants. We fit linear mixed models (N = 233) and discrete-time survival models (N = 154; 832 observations) to evaluate trajectories of Beck Depression Inventory (BDI) II scores and the incidence of new-onset moderate-to-severe depressive symptoms (BDI ≥ 17) among participants on combination antiretroviral therapy (cART), who were free of depression at study entry and received a minimum of three CSF examinations over 2496 person-months follow-up. Detectable CSF HIV RNA (threshold ≥50 copies/ml) at any visit was associated with a 4.7-fold increase in new-onset depression at subsequent visits adjusted for plasma HIV RNA and treatment adherence; hazard ratio (HR) = 4.76, (95 % CI 1.58-14.3); P = 0.006. Depression (BDI) scores were 2.53 points higher (95 % CI 0.47-4.60; P = 0.02) over 6 months if CSF HIV RNA was detectable at a prior study visit in fully adjusted models including age, sex, race, education, plasma HIV RNA, duration and adherence of CART, and lifetime depression diagnosis by Diagnostic Statistical Manual (DSM-IV) criteria. Persistent CSF but not plasma HIV RNA is associated with an increased risk for new-onset depression. Further research evaluating the role of immune activation and inflammatory markers may improve our understanding of this association.

Cocaine Use May be Associated with Increased Depression in Persons Infected with HIV.

HIV infection, depression, and cocaine use are independently associated with increased inflammatory signal production. There is increasing evidence about the role of inflammation in depression. In HIV disease, cocaine use may increase disease progression as well as alter T cell functioning resulting in cytokine activation and thereby increasing susceptibility to depression. We examined the association between cocaine use and depression among 447 African American persons infected with HIV who were frequent cocaine users or non-users, enrolled in an observational study in Baltimore, Maryland, between August 2003 and December 2012. The overall prevalence of depression was 40.9 % (183 of 447) participants. Among persons who were depressed, the prevalence of cocaine use was 81.4 % (149 of 183), compared to 69.3 % among persons who were not depressed (183 of 264), P = 0.004. Cocaine use was associated with nearly twofold increased odds of depression, unadjusted odds ratio (OR) 1.94, (95 % CI 1.23, 3.06); P = 0.004, compared to never using cocaine, and OR 1.02, (95 % CI 1.10, 1.05); P = 0.04 in adjusted analysis. A dose-response relationship between increasing duration of cocaine use and depression was observed. Frequency and duration of cocaine use may be associated with depression. We speculate that depression among cocaine users with HIV may involve an inflammatory component that needs further examination.

Cognitive impairment in patients with AIDS - prevalence and severity.

The advent of highly active antiretroviral therapy has prolonged the life expectancy of HIV patients and decreased the number of adults who progress to AIDS and HIV-associated dementia. However, neurocognitive deficits remain a pronounced consequence of HIV/AIDS. HIV-1 infection targets the central nervous system in subcortical brain areas and leads to high rates of delirium, depression, opportunistic central nervous system infections, and dementia. Long-term HIV replication in the brain occurs in astrocytes and microglia, allowing the virus to hide from antiviral medication and later compromise neuronal function. The associated cognitive disturbance is linked to both viral activity and inflammatory and other mediators from these immune cells that lead to the damage associated with HIV-associated neurocognitive disorders, a general term given for these disturbances. We review the severity and prevalence of the neuropsychiatric complications of HIV including delirium, neurobehavioral impairments (depression), minor cognitive-motor dysfunction, and HIV-associated dementia.

The cerebrospinal fluid HIV risk score for assessing central nervous system activity in persons with HIV.

Detectable human immunodeficiency virus (HIV) RNA in the cerebrospinal fluid (CSF) is associated with central nervous system (CNS) complications. We developed the CSF HIV risk score through prediction modeling to estimate the risk of detectable CSF HIV RNA (threshold >50 copies/mL) to help identify persons who might benefit most from CSF monitoring. We used baseline data from 1,053 participants receiving combination antiretroviral therapy who were enrolled in the 6-center, US-based CNS HIV Antiretroviral Therapy Effects Research (CHARTER) prospective cohort in 2004-2007. Plasma HIV RNA, CNS penetration effectiveness, duration of combination antiretroviral therapy, medication adherence, race, and depression status were retained correlates of CSF HIV RNA, displaying good discrimination (C statistic = 0.90, 95% confidence interval (CI): 0.87, 0.93) and calibration (Hosmer-Lemeshow P = 0.85). The CSF HIV risk score ranges from 0 to 42 points, with a mean of 15.4 (standard deviation, 7.3) points. At risk scores greater than 25, the probability of detecting CSF HIV RNA was at least 42.9% (95% CI: 36.6, 49.6). For each 1-point increase, the odds of detecting CSF HIV RNA increased by 26% (odds ratio = 1.26, 95% CI: 1.21, 1.31; P < 0.01). The risk score correlates with detection of CSF HIV RNA. It represents an advance in HIV management and monitoring of CNS effects, providing a potentially useful tool for clinicians.

Borderline personality disorder and chronic pain: a practical approach to evaluation and treatment.

Patients with chronic pain present a spectrum of complexity that can be overwhelming for the individual practitioner. These patients require thoughtful care and a comprehensive treatment plan. This complexity should be acknowledged, not avoided, and the patient should be engaged, not shunned. A practical approach will assist in developing expertise and proceeding empathically. The presence of a superimposed personality disorder significantly increases the difficulty of caring for these patients. Studies investigating the prevalence of borderline personality disorder in patients with chronic pain averaged 30 %, highlighting the importance of being able to effectively treat this patient population. Appropriate management of these patients should focus on a collaboration to practice productive behaviors despite intense emotional distress. Longitudinal research provides a foundation for an optimistic prognosis that can be enhanced with this rehabilitative approach.

Neuropsychiatric complications of aging with HIV.

Persons over age 50 are not only aging with human immunodeficiency virus (HIV) infection but also represent a high proportion of new HIV infections. Neuropsychiatric symptoms, including depression, cognitive impairment, and substance abuse, are very common in individuals infected with HIV. However, there is little understanding of the relationship between these HIV-related comorbid conditions in newly infected elderly patients compared to uninfected elderly and those who have survived after 20 years of HIV/AIDS. We summarize the current theories and research that link aging and HIV with psychiatric illnesses and identify emerging areas for improved research, treatment, and patient care.

Safety considerations in drug treatment of depression in HIV-positive patients: an updated review.

Major depressive disorder (MDD) is one of the most prevalent illnesses associated with HIV infection, and negatively affects medication adherence, disease progression and mortality in HIV disease. Co-morbid treatment of major depression in HIV disease is the optimal therapeutic approach, but discriminating MDD from normal fluctuations in mood state, personality or physiology is difficult. Definitive diagnosis of MDD is critical for drug safety and for avoiding unnecessary exposure to psychotropic medications. HIV patients respond to antidepressant treatment like the general population, and medication adverse effects and patient adherence are the best predictors of treatment outcome. This review attempts to assist the medical provider with the diagnosis and treatment of MDD in HIV patients. We outline the initial steps in screening and psychiatric referral, the antidepressants that are particularly useful in HIV-infected patients, and the adverse effects and pharmacological strategies for overcoming potential barriers to medication adherence. Potential interactions between the various classes of antidepressants and HIV/antiretroviral therapy, as well as management of HIV medication-related psychiatric adverse effects, are also discussed.

From stigmatized neglect to active engagement.

Chronic pain and substance abuse are common problems. Each entity represents a significant and independent burden to the patients affected by them, the healthcare system caring for them, and society at large supporting them. If the two problems occur together, all of these burdens and their consequences are magnified. Traditional treatments fail a substantial percentage of even the most straightforward cases. Clearly, new approaches are required for the most complex of cases. Success is possible only if multiple disciplines provide integrated care that incorporates all of the principles of substance abuse and chronic pain rehabilitation treatment into one package. While experience provides the foundation for implementing these programs, research that documents the methods behind successful outcomes will be needed to sustain support for them.

A behaviorist perspective.

Chronic pain is a sensory experience that produces suffering and functional impairment and is the result of both sensory input as well as secondary adaptation of the nervous system. The sensitization of the nervous system to pain is influenced by physical activity (or inactivity) and medication exposure. Medication taking and physical activity are behaviors that are increased or decreased by positive and negative reinforcement. Patients often have comorbid psychiatric conditions at presentation, including addictions, mood disorders, personality vulnerabilities and life circumstances that amplify their disability and impede their recovery. Behavioral conditioning contributes to chronic pain disorders in the form of both classical (Pavlov) and operant (Skinner) conditioning that increases the experience of pain, the liability to ongoing injury, the central amplification of pain, the use of reinforcing medications such as opiates and benzodiazepines, and behaviors associated with disability. The term 'abnormal illness behavior' has been used to describe behaviors that are associated with illness but are not explained physiologically. Behavioral conditioning often amplifies these abnormal behaviors in patients with chronic pain. Addiction can also be seen as a behavior that is reinforced and conditioned. The same factors that amplify abnormal illness behaviors also increase the liability to addiction. Psychiatric comorbidities also complicate and amplify abnormal illness behaviors and addictive behaviors and further contribute to the disability of chronic pain patients. Model interventions that reinforce healthy behaviors and extinguish illness behaviors are effective in patients with addictions and chronic pain. Maladaptive behaviors including addictive behaviors can be used as targets for classical and operant conditioning techniques, and these techniques are demonstrably effective in patients with chronic pain and addictions.

Optimizing treatment with opioids and beyond.

Patients with both chronic pain and substance use disorders offer special challenges and opportunities. They represent a large number of patients with significant costs to themselves and society that translate into poor outcome. The challenges in defining addiction in patients with chronic pain, particularly in those treated with chronic opioid therapy, have distracted the healthcare community from designing effective treatment programs. Traditional treatment programs for chronic pain disorders or substance use disorders are incapable of addressing the issues of the patients' 'other' problem. Treatment devolves to prescribing opioid medications with the belief that both disorders will be treated at least in part, which is deemed better than receiving no treatment at all. Patients are actually concerned about the risks of this type of treatment, and even if it did offer significant benefits, physicians demonstrate a lack of knowledge and skill in administering opioids to these patients. The inadequate treatment of either chronic pain or addiction interferes with the treatment of the other condition and necessitates the design of new treatment paradigms. A new approach to patients with both chronic pain and addiction should start with an evaluation and formulation of these patients to determine the different domains that contribute to their disability (diseases, dimensions, behaviors, life stories). A comprehensive formulation provides the appropriate platform for the implementation of an integrated program of therapy for both conditions that can be intensified to provide more, rather than less, care for the patient that does not meet the goals of functional rehabilitation.

Losing memories overnight: a unique form of human amnesia.

Since an automobile accident in 2005, patient FL has reported difficulty retaining information from one day to the next. During the course of any given day, she describes her memory as normal. However, memory for each day disappears during a night of sleep. She reports good memory for events that occurred before the accident. Although this pattern of memory impairment is, to our knowledge, unique to the medical literature, it was depicted in the fictional film "50 First Dates". On formal testing, FL performed moderately well when trying to remember material that she had learned during the same day, but she exhibited no memory at all for material that she knew had been presented on a previous day. For some tests, unbeknownst to FL, material learned on the previous day was intermixed with material learned on the same day as the test. On these occasions, FL's memory was good. Thus, she was able to remember events from earlier days when memory was tested covertly. FL performed differently in a number of ways from individuals who were instructed to consciously feign her pattern of memory impairment. It was also the impression of those who worked with FL that she believed she had the memory impairment that she described and that she was not intentionally feigning amnesia. On the basis of her neuropsychological findings, together with a normal neurological exam, normal MRI findings, and psychiatric evaluation, we suggest that FL exhibits a unique form of functional amnesia and that its characterization may have been influenced by knowledge of how amnesia was depicted in a popular film. She subsequently improved (and began retaining day-to-day memory) at Johns Hopkins University where she was in a supportive in-patient environment and was shown how to take control of her condition by interrupting her sleep at 4-h intervals.

Integrated opioid use disorder and HIV treatment: rationale, clinical guidelines for addiction treatment, and review of interactions of antiretroviral agents and opioid agonist therapies.

Injection drug use (IDU) is an important vector of HIV infection in the United States. Many patients with HIV infection have comorbid substance use disorders. Integrated treatment for HIV and substance use disorders has been shown to improve HIV and other health outcomes, but significant barriers to integrated treatment exist. For individuals who are dependent on injection opioid drugs, agonist therapies of methadone or buprenorphine maintenance are available as part of a treatment program. Patients who are infected with HIV and require antiretroviral therapy (ART) are at risk for drug-drug interaction between ART and methadone or buprenorphine. We present a programmatic approach to the evaluation and treatment of opioid use disorders for HIV care providers, as well as a summary of the available knowledge of interactions of methadone and buprenorphine with ART, along with the level of evidence for each actual or potential interaction. Based on the available information of practice and the level of clinical significance of drug-drug interactions, we conclude that buprenorphine-based maintenance treatment for opioid dependent patients is the preferred maintenance therapy for integrated treatment systems.