Systematic Review and Meta-Analysis: Do White Noise or Pink Noise Help With Task Performance in Youth With Attention-Deficit/Hyperactivity Disorder or With Elevated Attention Problems?

OBJECTIVE: Public interest in the potential benefits of white, pink, and brown noise for attention-deficit/hyperactivity disorder (ADHD) has recently mushroomed. White noise contains all frequencies of noise and sounds like static; pink or brown noise has more power in the lower frequencies and may sound, respectively, like rain or a waterfall. This meta-analysis evaluated effects on laboratory tasks in individuals with ADHD or elevated ADHD symptoms. METHOD: Eligible studies reported on participants with diagnosis of ADHD or elevated symptoms of ADHD who were assessed in a randomized trial using laboratory tasks intended to measure aspects of attention or academic work involving attention or executive function while exposed to white, pink, and brown noise and compared with a low/no noise condition. Two authors independently reviewed and screened studies for eligibility. A random-effects meta-analysis was conducted with preplanned moderator analyses of age, diagnostic status, and task type. Publication bias was evaluated. The GRADE tool was used to assess certainty of the evidence. Sensitivity analyses were conducted to evaluate robustness. RESULTS: Studies of children and college-age young adults with ADHD or ADHD symptoms (k = 13, N = 335) yielded a small but statistically significant benefit of white and pink noise on task performance (g = 0.249, 95% CI [0.135, 0.363], p < .0001). No studies of brown noise were identified. Heterogeneity was minimal, and moderators were nonsignificant; results survived sensitivity tests, and no publication bias was identified. In non-ADHD comparison groups (k = 11, N = 335), white and pink noise had a negative effect (g = -0.212, 95% CI [-0.355, -0.069], p = .0036). CONCLUSION: White and pink noise provide a small benefit on laboratory attention tasks for individuals with ADHD or high ADHD symptoms, but not for non-ADHD individuals. This article addresses theoretical implications, cautions, risks, and limitations. STUDY PREREGISTRATION INFORMATION: White Noise for ADHD: A Systematic Review And Meta-analysis; https://www.crd.york.ac.uk/prospero; CRD42023393992.

The Relationship Between Emotion Dysregulation and Error Monitoring in Adolescents with ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is emblematic of the limitations of existing diagnostic categories. One potential solution, consistent with the Research Domain Criteria (RDoC) initiative, is to interrogate psychological mechanisms at the behavioral and physiological level together to try and identify meaningful subgroups within existing categories. Such approaches provide a way to revise diagnostic boundaries and clarify individual variation in mechanisms. Here, we illustrate this approach to help resolve heterogeneity in ADHD using a combination of behaviorally-rated temperament measures from the Early Adolescent Temperament Questionnaire; cognitive performance on three difference conditions of an emotional go/no-go task; and electroencephalogram (EEG)-measured variation in multiple stages of error processing, including the error-related negativity (ERN) and positivity (Pe). In a large (N = 342), well-characterized sample of adolescents with ADHD, latent profile analysis identified two ADHD temperament subgroups: 1) emotionally regulated and 2) emotionally dysregulated (with high negative affect). Cognitive and EEG assessment in a subset of 272 adolescents (nADHD = 151) found that the emotionally dysregulated group showed distinct patterns of change in early neural response to errors (ERN) across emotional task conditions as compared to emotionally-regulated ADHD adolescents and typically-developing controls. Both ADHD groups showed blunted later response to errors (Pe) that was stable across emotional task conditions. Overall, neural response patterns identified important differences in how trait and state emotion interact to affect cognitive processing. Results highlight important temperament variation within ADHD that helps clarify its relationship to the ERN, one of the most prominent putative neural biomarkers for psychopathology.

Immunomodulation by tramadol combined with acetaminophen or dexketoprofen: In vivo animal study.

Among other functions, macrophages remove foreign particles, including medications, from the circulation, making them an important target for immunomodulatory molecules. Currently, growing evidence suggests that analgesics affect the activity of immune cells not directly related to pain, and thus may induce unwanted immunosuppression in patients at risk. However, the immunomodulatory effects resulting from macrophage targeting by these drugs are understudied. Therefore, the current study investigated the immune effects induced in healthy mice by repeated administration of tramadol alone or in combination with acetaminophen or dexketoprofen. We observed that drug administration decreased the percentage of infiltrating macrophages in favor of resident macrophages in peritoneal exudates. While all drugs reduced the number of infiltrating macrophages that phagocytosed sheep red blood cells (SRBC), their administration increased the effectiveness of phagocytosis, and treatment with acetaminophen with or without tramadol elevated the expression of MHC class II by Mac3+ macrophages. Interestingly, SRBC-pulsed macrophages from mice treated with tramadol combined with acetaminophen potently activated SRBC-specific B cells in humoral response, and administration of these drugs to recipients of contact hypersensitivity effector cells augmented the resulting cellular immune response. In addition, tramadol administered alone or with dexketoprofen enhanced the spontaneous release of pro-inflammatory cytokines by macrophages. Our current research findings demonstrate that tramadol therapy in combination with acetaminophen or dexketoprofen has a relatively low risk of causing immunosuppressive side effect because the drugs slightly reduce the inflammatory reaction of macrophages but do not impair their ability to activate the adaptive immune responses.

Joint polygenic and environmental risks for childhood attention-deficit/hyperactivity disorder (ADHD) and ADHD symptom dimensions.

Background: attention-deficit/hyperactivity disorder (ADHD) is associated with both polygenic liability and environmental exposures, both intrinsic to the family, such as family conflict, and extrinsic, such as air pollution. However, much less is known about the interplay between environmental and genetic risks relevant to ADHD-a better understanding of which could inform both mechanistic models and clinical prediction algorithms. Methods: Two independent data sets, the population-based Adolescent Brain Cognitive Development Study (ABCD) (N = 11,876) and the case-control Oregon-ADHD-1000 (N = 1449), were used to examine additive (G + E) and interactive (GxE) effects of selected polygenic risk scores (PRS) and environmental factors in a cross-sectional design. Genetic risk was measured using PRS for nine mental health disorders/traits. Exposures included family income, family conflict/negative sentiment, and geocoded measures of area deprivation, lead exposure risk, and air pollution exposure (nitrogen dioxide and fine particulate matter). Results: ADHD PRS and family conflict jointly predicted concurrent ADHD symptoms in both cohorts. Additive-effects models, including both genetic and environmental factors, explained significantly more variation in symptoms than any individual factor alone (joint R 2 = .091 for total symptoms in ABCD; joint R 2 = .173 in Oregon-ADHD-1000; all delta-R 2 p-values <2e-7). Significant effect size heterogeneity across ancestry groups was observed for genetic and environmental factors (e.g., Q = 9.01, p = .011 for major depressive disorder PRS; Q = 13.34, p = .001 for area deprivation). GxE interactions observed in the full ABCD cohort suggested stronger environmental effects when genetic risk is low, though they did not replicate. Conclusions: Reproducible additive effects of PRS and family environment on ADHD symptoms were found, but GxE interaction effects were not replicated and appeared confounded by ancestry. Results highlight the potential value of combining exposures and PRS in clinical prediction algorithms. The observed differences in risks across ancestry groups warrant further study to avoid health care disparities.

Personal fear of their own death and determination of philosophy of life affects the breaking of bad news by internal medicine and palliative care clinicians.

Introduction: Patients with life-threatening disease should be informed about the diagnosis and prognosis of life-expectancy. Breaking bad news (BBN) by a clinician may be affected not only by their lack of communication skills but also their philosophy of life, beliefs, fear of their own death, their length of tenure, and their exposure to dying and death. Material and methods: This questionnaire-based study aimed to investigate the impact of these factors on BBN in internal medicine practitioners (INT) versus palliative care physicians (PCP), and to detect the possible impediments to the proper communication process and the clinicians' needs regarding their preparation for such a conversation. Results: Thirty-eight PCPs and 64 INTs responded. Determination of philosophy of life, but not religiousness, positively correlated with the number of working years in palliative care. Two-thirds of the respondents declared fear of death, and it diminishes along with working years, especially in palliative care. For most physicians, BBN appeared difficult; however, less so for PCPs, persons with a high level of determination of philosophy of life, and men. The most frequent impediment was insufficient communication skills. Consistently, the respondents expressed the need for closing the gap in communication skills, especially by mentoring or training on communication. Conclusions: Fear of death may restrain inexperienced medical professionals from BBN to patients and makes it difficult. Working in palliative care augments the determination of philosophy of life and diminishes fear of death. The higher the determination of philosophy of life, the more likely BBN is to be performed. Philosophy of life, spirituality, and communication skills should be addressed in postgraduate education.

Temperament in middle childhood questionnaire: New data on factor structure and applicability in a child clinical sample.

The Temperament in Middle Childhood Questionnaire (TMCQ) is one of a family of instruments representing one of the major conceptual models of child temperament. The present study reports new psychometric information on the TMCQ using a larger sample than in prior factor-analytic studies of this instrument. Data from parent ratings of 1,418 children were utilized. The sample of community volunteers included 697 typically developing youth and 721 defined by research diagnostic procedures as having attention-deficit/hyperactivity disorder. Results failed to support the original proposed structure of the TMCQ, but found support for a structure with 12 subscales that confirmed a substantial portion of the lower order factor structure. However, the intended three-factor higher order structure was not able to be fully recovered. Two-group invariance was supported in the final model, supporting use in studies of typical and atypical development. In conclusion, with some modifications the TMCQ remains a useful research measure at the lower order factor level. The validity of the higher order structure is less clear, likely due to measure-specific limitations, and suggests a need for some refinement to the measure. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Itopride increases the effectiveness of the management of opioid-induced constipation in palliative care patients: an observational non-interventional study.

Introduction: It is strongly recommended that laxatives be routinely prescribed for the prevention of opioid-induced constipation (OIC). The evidence supporting the effectiveness of prokinetics for this indication is sparse. This study aims to verify if itopride, added to preventive OIC therapy, increases the effectiveness of the prevention of opioid-induced constipation in adult palliative care patients. Material and methods: In a questionnaire-based observational study, all patients received regular laxatives plus one of the following: oxycodone/naloxone (OXN); itopride (ITP); or oxycodone/naloxone + itopride (OXN + ITP). The primary measure was the decrease in the necessity of laxative use in a 0-4 scale assessed after 7 days of treatment. Results: Ninety-two patients met the inclusion criteria in the four groups: OXN (n = 12), ITP (11), OXN + ITP (9), and the control group (laxatives only if needed) (60). The necessity of laxatives decreased in groups where itopride was used, with a statistically significant difference versus control, oxycodone/naloxone (p = 0.009), or in combination. The OXN did not decrease laxative use (p = 0.22). Conclusions: All interventions appeared similarly effective in the prevention of OIC. However, adding itopride, but not oxycodone/naloxone, resulted in a decrease in the necessity of laxative use in OIC patients, and it seems to be valuable in this often refractory condition. Randomised, controlled trials would be valuable to obtain good quality evidence without systematic bias.

Efficacy of Eat Breathe Thrive: A randomized controlled trial of a yoga-based program.

Evidence positions yoga as a promising intervention for enhancing positive embodiment and supporting the prevention of, and recovery from, eating disorders (EDs) by reducing ED symptomatology and building skills that facilitate an ongoing, embodied sense of wellbeing. However, yoga-based programs are few and rigorous literature on their efficacy is limited. This study examined the efficacy and feasibility of a yoga-based program called Eat Breathe Thrive (EBT) which aims to prevent EDs and support embodiment. Participants (N = 168, 93.5 % women) from a community sample in the United States and United Kingdom, ages 18-65, were randomly allocated to a 2-h, 7-week EBT program or waitlist-control condition. Compared to controls, EBT participants experienced significant decreases in ED behaviors, depression, and difficulties regulating emotions. They reported significantly greater use of mindfulness skills, such as interoceptive awareness, mindful self-care, and mindful eating. After a single session, participants reported immediate improvement in their sense of well-being, indicating increased state positive embodiment. Most effects were sustained at 6-month follow-up. The majority of individuals attended most sessions. Self-reported treatment integrity was excellent. Directions for future research are proposed. Results support the efficacy and feasibility of an integrated yoga intervention that fosters positive ways of inhabiting the body.

Opioid prescribing attitudes of palliative care physicians versus other specialists: a questionnaire-based survey.

PURPOSE OF THE STUDY: While opioid overuse is a public health crisis in the USA, opioid analgesics are used suboptimally in Central and Eastern Europe, causing many pain cases to remain untreated or undertreated. STUDY DESIGN: This questionnaire study aimed to identify the prevalent prescribing patterns and attitudes and the possible internal impediments to optimal opioid use among palliative care physicians and other specialists in Poland. RESULTS: Tramadol was the most commonly preferred opioid. While palliative care physicians (n=81) used various strong opioids, other physicians (n=87) prescribed mostly buprenorphine, accessible with standard prescription forms. Neither internal prejudices and beliefs nor administrative regulations impede prescribing opioids by palliative care physicians, unlike specialists other than palliative medicine. Special prescription forms for psychoactive medications, fear of drug addiction of their patients and penalties for possible errors on prescriptions affect the latter's optimal prescribing. They also revealed significant gaps in the knowledge of prescribing opioids and would take part in additional training. Palliative care physicians appeared optimally prepared for cancer pain management and report fewer internal barriers than other specialists. CONCLUSIONS: Continuous medical education on cancer pain treatment should be provided to all specialists to ensure optimal opioid pharmacotherapy and avoid overprescribing or underprescribing opioids. Administrative restrictions are the main barrier to optimal pain treatment.

Reduction of Glut1 in the Neural Retina But Not the RPE Alleviates Polyol Accumulation and Normalizes Early Characteristics of Diabetic Retinopathy.

Hyperglycemia is a key determinant for development of diabetic retinopathy (DR). Inadequate glycemic control exacerbates retinopathy, while normalization of glucose levels delays its progression. In hyperglycemia, hexokinase is saturated and excess glucose is metabolized to sorbitol by aldose reductase via the polyol pathway. Therapies to reduce retinal polyol accumulation for the prevention of DR have been elusive because of low sorbitol dehydrogenase levels in the retina and inadequate inhibition of aldose reductase. Using systemic and conditional genetic inactivation, we targeted the primary facilitative glucose transporter in the retina, Glut1, as a preventative therapeutic in diabetic male and female mice. Unlike WT diabetics, diabetic Glut1+/- mice did not display elevated Glut1 levels in the retina. Furthermore, diabetic Glut1+/- mice exhibited ameliorated ERG defects, inflammation, and oxidative stress, which was correlated with a significant reduction in retinal sorbitol accumulation. Retinal pigment epithelium-specific reduction of Glut1 did not prevent an increase in retinal sorbitol content or early hallmarks of DR. However, like diabetic Glut1+/- mice, reduction of Glut1 specifically in the retina mitigated polyol accumulation and diminished retinal dysfunction and the elevation of markers for oxidative stress and inflammation associated with diabetes. These results suggest that modulation of retinal polyol accumulation via Glut1 in photoreceptors can circumvent the difficulties in regulating systemic glucose metabolism and be exploited to prevent DR.SIGNIFICANCE STATEMENT Diabetic retinopathy affects one-third of diabetic patients and is the primary cause of vision loss in adults 20-74 years of age. While anti-VEGF and photocoagulation treatments for the late-stage vision threatening complications can prevent vision loss, a significant proportion of patients do not respond to anti-VEGF therapies, and mechanisms to stop progression of early-stage symptoms remain elusive. Glut1 is the primary facilitative glucose transporter for the retina. We determined that a moderate reduction in Glut1 levels, specifically in the retina, but not the retinal pigment epithelium, was sufficient to prevent retinal polyol accumulation and the earliest functional defects to be identified in the diabetic retina. Our study defines modulation of Glut1 in retinal neurons as a targetable molecule for prevention of diabetic retinopathy.

A novel, small peptide with activity against human pancreatic cancer.

KTH-222 is a novel, 8-amino acid length peptide. It is derived from a motif identified in a group of peptides that are related to atrial natriuretic peptide and that are able to inhibit cancer cell growth. We report here that KTH-222 inhibits the attachment, proliferation, and development of an invasive morphology in cultured human pancreatic tumor cells (MIA PaCa-2 and HPAC). At a biochemical level, it inhibits tubulin polymerization which may underlie these cellular effects. We further report that KTH-222 reduces the rate of tumor growth and prolongs survival in mice implanted with MIA PaCa-2 cells. In this model system, KTH-222 is more effective than gemcitabine, a drug commonly used in the treatment of pancreatic cancer. Furthermore, KTH-222 does not decrease the rate of weight gain in the treated mice, suggesting the absence of gross toxicity. These activities of KTH-222 suggest that it may be useful in the treatment of pancreatic cancer.

Palliative Performance Scale: cross cultural adaptation and psychometric validation for Polish hospice setting.

BACKGROUND: Measuring functional status in palliative care may help clinicians to assess a patient's prognosis, recommend adequate therapy, avoid futile or aggressive medical care, consider hospice referral, and evaluate provided rehabilitation outcomes. An optimized, widely used, and validated tool is preferable. The Palliative Performance Scale Version 2 (PPSv2) is currently one of the most commonly used performance scales in palliative settings. The aim of this study is the psychometric validation process of a Polish translation of this tool (PPSv2-Polish). METHODS: Two hundred patients admitted to a free-standing hospice were evaluated twice, on the first and third day, for test-retest reliability. In the first evaluation, two different care providers independently evaluated the same patient to establish inter-rater reliability values. PPSv2-Polish was evaluated simultaneously with the Karnofsky Performance Score (KPS), Eastern Cooperative Oncology Group (ECOG) Performance Status (ECOG PS), and Barthel Activities of Daily Living (ADL) Index, to determine its construct validity. RESULTS: A high level of full agreement between test and retest was seen (63%), and a good intra-class correlation coefficient of 0.85 (P < 0.0001) was achieved. Excellent agreement between raters was observed when using PPSv2-Polish (Cohen's kappa 0.91; P < 0.0001). Satisfactory correlations with the KPS and good correlations with ECOG PS and Barthel ADL were noticed. Persons who had shorter prognoses and were predominantly bedridden also had lower scores measured by the PPSv2-Polish, KPS and Barthel ADL. A strong correlation of 0.77 between PPSv2-Polish scores and survival time was noted (P < 0.0001). Moderate survival correlations were seen between KPS, ECOG PS, and Barthel ADL of 0.41; - 0.62; and 0.58, respectively (P < 0.0001). CONCLUSION: PPSv2-Polish is a valid and reliable tool measuring performance status in a hospice population and can be used in daily clinical practice in palliative care and research.

Analgesic adjuvants modulate morphine-induced immune effects in mice.

BACKGROUND: Macrophages, involved in the pathogenesis of pain, express a variety of receptors enabling responsiveness to certain medications, including adjuvant analgesics (AAs), that are effective in neuropathic pain and include drugs not primarily indicated for pain treatment, such as anticonvulsants or antidepressants. Their analgesic effects are likely associated with immunomodulatory activity, that remain undefined. Thus, current research aimed at examining the impact of AAs on morphine-induced effects exerted on mouse immunity. METHODS: Macrophages from mice treated with morphine with or without gabapentin, amitriptyline or venlafaxine, were either subjected to phagocytosis assay, cultured to evaluate the generation of cytokines, or were pulsed with either corpuscular antigen or hapten and transferred to naive recipients to induce humoral or cellular response, respectively. Active contact hypersensitivity was also elicited in drug-treated mice. RESULTS: We observed that repeatedly administered morphine and AAs reduced antigen phagocytosis by macrophages. Further, amitriptyline with morphine enhanced basal secretion of cytokines by macrophages, and all drugs tended to decrease LPS-stimulated release of pro-inflammatory cytokines. Morphine and AAs impacted the expression of phagocytosis and antigen-presentation markers on macrophages, which led to the reduced ability of morphine-affected macrophages to induce B-cell secretion of specific antibodies, and the addition of AAs strengthened this effect. Finally, gabapentin and venlafaxine suppressed the contact hypersensitivity reaction, while amitriptyline seemed to have the opposite effect. CONCLUSIONS: Our study demonstrated a significant anti-inflammatory activity of AAs across a broad spectrum of macrophage immune functions, which is likely critical to their analgesic activity supporting the beneficial effect of morphine.

Endogenous insulin signaling in the RPE contributes to the maintenance of rod photoreceptor function in diabetes.

In diabetes, there are two major physiological aberrations: (i) Loss of insulin signaling due to absence of insulin (type 1 diabetes) or insulin resistance (type 2 diabetes) and (ii) increased blood glucose levels. The retina has a high proclivity to damage following diabetes, and much of the pathology seen in diabetic retinopathy has been ascribed to hyperglycemia and downstream cascades activated by increased blood glucose. However, less attention has been focused on the direct role of insulin on retinal physiology, likely due to the fact that uptake of glucose in retinal cells is not insulin-dependent. The retinal pigment epithelium (RPE) is instrumental in maintaining the structural and functional integrity of the retina. Recent studies have suggested that RPE dysfunction is a precursor of, and contributes to, the development of diabetic retinopathy. To evaluate the role of insulin on RPE cell function directly, we generated a RPE specific insulin receptor (IR) knockout (RPEIRKO) mouse using the Cre-loxP system. Using this mouse, we sought to determine the impact of insulin-mediated signaling in the RPE on retinal function under physiological control conditions as well as in streptozotocin (STZ)-induced diabetes. We demonstrate that loss of RPE-specific IR expression resulted in lower a- and b-wave electroretinogram amplitudes in diabetic mice as compared to diabetic mice that expressed IR on the RPE. Interestingly, RPEIRKO mice did not exhibit significant differences in the amplitude of the RPE-dependent electroretinogram c-wave as compared to diabetic controls. However, loss of IR-mediated signaling in the RPE reduced levels of reactive oxygen species and the expression of pro-inflammatory cytokines in the retina of diabetic mice. These results imply that IR-mediated signaling in the RPE regulates photoreceptor function and may play a role in the generation of oxidative stress and inflammation in the retina in diabetes.

Data supporting the understanding of modulatory function of opioid analgesics in mouse macrophage activity.

The data presented herein expand the current understanding of the modulatory function of opioid drugs in mouse macrophage activity described in our relevant research article (Filipczak-Bryniarska et al., 2017) [1], in which we characterize the influence of morphine, buprenorphine and oxycodone on humoral and cell-mediated immune response in mice. Among other things, we have shown the effects of treatment with assayed analgesics on macrophage ability to induce antigen-specific B-cell response to sheep red blood cells as well as to generate reactive oxygen intermediates and nitric oxide. The current data demonstrate the effects of morphine, buprenorphine or oxycodone administration on phagocytosis of sheep red blood cells and zymosan by mouse macrophages, supplementing the data on immune modulatory capacities of assayed drugs, recently reported by us (Filipczak-Bryniarska et al., 2017; Kozlowski et al., 2017) [1,2].

In contrast to morphine, buprenorphine enhances macrophage-induced humoral immunity and, as oxycodone, slightly suppresses the effector phase of cell-mediated immune response in mice.

BACKGROUND: Opioid receptors are commonly expressed on various immune cells, macrophages especially. Thus, these cells are prone to stimulation with opioids, which seems to be responsible for opioid-induced immunomodulatory effects. While morphine, fentanyl and methadone influence on mouse immune response was recently studied, little is known about the potential immunomodulatory impact of buprenorphine and oxycodone. AIM: The current research aimed to investigate the influence of buprenorphine and oxycodone on immune responses in mice under homeostatic conditions. METHODS AND RESULTS: Repeated administration of morphine led to intensification of CHS response in actively sensitized mice, while buprenorphine or oxycodone administration exerted the opposite effect. Further, hapten-conjugated macrophages from mice treated with morphine, when transferred into naive recipients, induced more potent CHS response. The enhanced generation of reactive oxygen intermediates and nitric oxide by macrophages from mice treated with buprenorphine, oxycodone or morphine was also shown, along with increased release of IL-6, TNFα and TGFß. Treatment with opioids altered expression of antigen phagocytosis and presentation markers. Finally, the inhibitory effect of morphine treatment on induction of humoral immunity by macrophages was demonstrated, while oxycodone failed to influence humoral immune response and buprenorphine actually enhanced B-cell activation. CONCLUSIONS: Current observations confirm that macrophages greatly contribute to immunomodulatory effects of opioids. Studies on immunomodulation by opioids have great importance related to the evaluation of its beneficial and adverse effects on patient condition. Our research showed that oxycodone exerts the weakest immunomodulatory properties, allowing us to assume this drug as safer than morphine during prolonged therapy.

Evaluation of prognostic factors, symptoms and consequences of dehydration in patients with cancer based on retrospective data analysis of 102 patients treated in the Department of Palliative Medicine at the University Hospital in Cracow - preliminary report.

INTRODUCTION: Dehydration is a common problem in patients with terminal cancer patients. It worsens the quality of life and increases the amount of complications. Factors associated with dehydration need further exploration. The aim of our study was to determine the predictors of dehydration. PATIENTS AND METHODS: 102 terminal cancer patients admitted to Palliative Care Unit were retrospectively analyzed. Detailed physical examination, medical history including history taken from family and care givers was taken upon admission. Laboratory parameters including morphology, sodium, potassium, total and ionized calcium, LDH were taken on admission. We used univariate and multivariate logistic regression analysis to determine factors associated with dehydration. RESULTS: On admission 39% of patients were diagnosed with dehydration. Multivariate logistic regression analysis after adjustment for possible confounders reviled that lack of family care (p = 0.006; OR = 0.147; CI 95% = 0.038-0.577), higher level of PS (p = 0.0426; OR = 1.65; CI 95% = 1.017-2.667), lack of prior opioid use (p = 0.0233; OR = 0.386; CI 95% = 0.17-0.897), occurrence of nausea and vomiting at admission (p = 0.0077; OR = 3.297; CI 95% = 1.372-7.922), occurrence of dyselectrolytemia (p = 0.0012; OR = 4.462; CI 95% = 1.81-10.997), lack of prior GKS use (p = 0.0362; OR = 0.339; CI 95% = 0.123-0.933); lack of prior NSAID use (p = 0.0255; OR = 0.265; CI 95% = 0.082-0.849) remained independently associated with dehydration. CONCLUSIONS: Lack of family care, lack of prior opioid use, higher level of PS, occurrence of nausea and vomiting at admission, occurrence of dyselectrolytemia, lack of prior GKS use and lack of prior NSAID use in patients with terminal cancer are factors associated with dehydration.

The impact of advanced opioid drugs and analgesic adjuvants on murine macrophage oxygen burst.

Macrophages (Mf) are a versatile group of phagocytic cells responsible for fulfilling a variety of immune functions, most notably for mounting the initial anti-microbial response and for the clearance of cellular debris and apoptotic bodies. The key processes for fulfilling these functions include the production of reactive oxygen intermediates (ROIs) and nitric oxide (NO). Mf also express a variety of receptors, including opioid, serotonin, and norepinephrine receptors, and thus can react to various substances. Our study aimed to examine the effects of oxycodone and buprenorphine on the production ROIs and NO by Mf from intraperitoneally-treated mice, as compared to the previously studied morphine, fentanyl, and methadone, as well as the effects of the analgesic adjuvants gabapentin, amitriptyline, and venlafaxine. ROIs was estimated via luminol and lucigenin dependent chemiluminescence assay, and NO secretion was estimated via a colorimetric method utilizing a modified Griess reaction. We observed an overall decrease in both ROIs and NO production by Mf from adjuvant-treated mice, especially with amitriptyline. Opioids, however, resulted in enhanced ROIs production and mixed NO secretion, with oxycodone and buprenorphine have the least immunomodulatory effects. As ROIs and NO are potent mediators of Mf activity during the innate immune response, our current results express great translational potential. Our results suggest that OPs administration may boost Mf anti-microbial response. On the other hand, during sterile in ammation, enhanced generation of ROIs by Mf influenced by opioids may increase the risk of tissue damage, but co-administration of adjuvants could abolish this adverse effect.

The role of macrophages in anti-inflammatory activity of antidepressant drugs.

Depression is a common disease influencing patients' quality of life, whose etiology involves complex interactions of environmental, genetic and immunological factors. The latter factors include proinflammatory activation of monocytes and macrophages and increased serum levels of proinflammatory cytokines, altogether formulated as the "macrophage theory of depression". Our current review summarizes the impact of the most commonly used antidepressant drugs on the immune response with special emphasis on the role of macrophages in the clinically observed effects. The anti-inflammatory action of antidepressants mainly results from their direct interaction with immune cells and from changes in the concentration and the relations of neurotransmitters sensed by these cells. The summarized data revealed that Mφs are one of the leading cell populations involved in drug-mediated immune effects that can be observed both in subjects with depression as well as in individuals not suffering from depression. Thus, currently reviewed immunomodulatory effects of the experimental use of different antidepressant drugs suggest the possibility of utilizing them in complex therapeutic strategies dedicated to various inflammatory and immune-mediated diseases. It is worth noting that an excessive inflammatory reaction is also associated with the pathogenesis of various cardiovascular, metabolic and neuro-endocrine diseases. Thus, the inclusion of antidepressants in the complex therapy of these disorders may have beneficial effects through the enhancement of the mood of the patient and alleviation of chronic inflammation. On the other hand, presented data suggest that the influence of chronically used antidepressants on anti-microbial and anti-tumor immunity could also be taken into consideration.

Adult tonsillectomy: postoperative pain depends on indications / Tonsilectomia no adulto: a dor pós-operatória depende das indicações

ABSTRACT INTRODUCTION: Intense pain is one of the most important postoperative complaints after tonsillectomy. It is often described by patients as comparable to the pain that accompanies an acute tonsillitis. Although recurrent tonsillitis is the most frequent indication for surgery, many tonsillectomies are performed due to other indications and these patients may be unfamiliar with such pain. OBJECTIVE: To verify whether individuals with recurrent tonsillitis experience different post-tonsillectomy pain intensity than those with other indications for surgery, with no history of episodes of acute tonsillitis. METHODS: A total of 61 tonsillectomies were performed under general anesthesia, using a potassium titanyl phosphate (KTP) laser (to eliminate the potential influence on the study results of forceful dissection of fibrotic tonsils in patients with history of recurrent tonsillitis) and multiple ligations of blood vessels within the tonsillar beds. The patients received 37.5 mg Tramadoli hydrochloridum + 325 mg Paracetamol tablets for 10 days. Postoperative variables included the duration of hospital stay, postoperative hemorrhage and readmission rate. The patients reported pain intensity on consecutive days, pain duration, weight loss on postoperative day 10, character, intensity and duration of swallowing difficulties, and the need for additional doses of painkillers. Healing was also assessed. Capsular nerve fibers were histologically examined in the resected tonsils by immunostainings for general and sensory markers. RESULTS: Indications for the surgery were: recurrent acute tonsillitis (34 patients), no history of recurrent tonsillitis: focus tonsil (20) and intense malodour (7). Pain intensity on postoperative days 3-4 and incidence of readmissions due to dehydration were significantly higher in the group with no history of recurrent tonsillitis. No significant differences in relative densities of protein gene product (PGP) 9.5- and calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers were observed. CONCLUSION: Patients with recurrent tonsillitis qualified for tonsillectomy reported lower pain intensity than those without recurrent tonsillitis and the pain scores were unrelated to nerve fibers density.

Resumo Introdução: Dor intensa é uma das queixas mais importantes no pós-operatório de uma tonsilectomia. Com frequência, essa dor é descrita pelos pacientes, como comparável à dor que acompanha a tonsilite aguda. Apesar da tonsilite recorrente ser a indicação mais frequente para cirurgia, muitas tonsilectomias são realizadas por outras indicações, e esses pacientes podem não estar familiarizados com essa dor. Objetivo: Verificar se indivíduos com tonsilite recorrente apresentam diferenças na intensidade dolorosa pós-tonsilectomia vs. pacientes com outras indicações para cirurgia, sem histórico de episódios de tonsilite aguda. Método: Foram realizadas 61 tonsilectomias sob anestesia geral, com o uso de um laser potassium titanyl phosphate (KTP) (para que fosse eliminada uma possível influência de uma dissecção agressiva das tonsilas fibrosadas em pacientes com história de tonsilite recorrente), e hemostasia através de ligaduras de vasos sanguíneos nos leitos tonsilares. Os pacientes foram medicados com 37,5 mg de cloridrato de tramadol + 325 mg de paracetamol (comprimidos) durante 10 dias. As variáveis pós-operatórias foram tempo de internação hospitalar, hemorragia e percentual de readmissão. Os pacientes forneceram informações sobre a intensidade da dor em dias consecutivos, duração da dor, perda de peso corpóreo no dia 10 do pós-operatório, intensidade e duração da dificuldade de deglutição, e necessidade de doses adicionais de analgésicos. A velocidade de cicatrização também foi avaliada. Fibras nervosas capsulares foram examinadas histologicamente nas tonsilas resecadas com o uso de imunocorantes para marcadores de fibras nervosas gerais e de sensibilidade. Resultados: As indicações para a cirurgia foram: tonsilite aguda recorrente (34 pacientes), ausência de história de tonsilite recorrente - Tonsilite focal (20) e halitose (7). A intensidade da dor nos dias 3-4 do pós-operatório e a incidência de reinternações em decorrência de desidratação foram significativamente mais altas no grupo sem história de tonsilite recorrente. Não foram observadas diferenças significantes nas densidades relativas de fibras nervosas imunorreativas para protein gene product (PGP) 9.5 e calcitonin gene-related peptide (CGRP). Conclusão: Os pacientes com tonsilite recorrente e qualificados para tonsilectomia informaram menor intensidade da dor em relação aos pacientes sem histórico se tonsilite recorrente, e os escores para dor não apresentaram relação com a densidade das fibras nervosas.