Comorbid Medical Illness Research Articles

Obinutuzumab for the treatment of chronic lymphocytic leukemia.

Obinutuzumab is a novel therapeutic anti-CD20 monoclonal antibody recently approved by the United States Food and Drug Administration (FDA) for use in combination with chlorambucil as first-line treatment of chronic lymphocytic leukemia (CLL). It is distinguished from other anti-B-lymphocyte antigen CD20 (anti-CD20) therapeutic antibodies in current clinical use by its type II properties and glycoengineered Fc region. In vitro these unique properties translate into higher rates of antibody-dependent cytotoxicity and direct cell death compared to rituximab, and obinutuzumab demonstrates improved efficacy in human lymphoma xenograft models and whole blood lymphocyte depletion assays. FDA approval was based upon results from a randomized phase III trial comparing treatment with single-agent chlorambucil to the combination of chlorambucil and either rituximab or obinutuzu-mab. The obinutuzumab arm resulted in higher rates of complete remission and significant improvements in progression-free survival versus either comparator regimen. The majority of patients in the obinutuzumab and chlorambucil arm finished all six planned treatment cycles, and therapy was well tolerated. Toxicities of obinutuzumab are similar to those of other anti-CD20 antibodies, although infusion-related reactions and neutropenia appear to be more common. This trial establishes chemoimmunotherapy with obinutuzumab and chlorambucil as an attractive treatment option for CLL patients, particularly those with comorbid medical illnesses or advanced age. Obinutuzumab remains under study in combination with both chemotherapy and novel agents for CLL and non-Hodgkin's lymphoma, where it is expected to find additional clinical applications.

Upper esophageal sphincter abnormalities are strongly predictive of treatment response in patients with achalasia.

To investigate the relationship between upper esophageal sphincter abnormalities achalasia treatment We performed a retrospective study of 41 consecutive patients referred for high resolution esophageal manometry with a final manometric diagnosis of achalasia. Patients were sub-divided by presence or absence of Upper esophageal sphincter (UES) abnormality, and clinical and manometric profiles were compared. Correlation between UES abnormality and sub-type (i.e., hypertensive, hypotensive or impaired relaxation) and a number of variables, including qualitative treatment response, achalasia sub-type, co-morbid medical illness, psychiatric illness, surgical history, dominant presenting symptom, treatment type, age and gender were also evaluated. Among all 41 patients, 24 (58.54%) had a UES abnormality present. There were no significant differences between the groups in terms of age, gender or any other clinical or demographic profiles. Among those with UES abnormalities, the majority were either hypertensive (41.67%) or had impaired relaxation (37.5%) as compared to hypotensive (20.83%), although this did not reach statistical significance (P = 0.42). There was no specific association between treatment response and treatment type received; however, there was a significant association between UES abnormalities and treatment response. In patients with achalasia and concomitant UES abnormalities, 87.5% had poor treatment response, while only 12.5% had favorable response. In contrast, in patients with achalasia and no UES abnormalities, the majority (78.57%) had good treatment response, as compared to 21.43% with poor treatment response (P = 0.0001). After controlling for achalasia sub-type, those with UES abnormality had 26 times greater odds of poor treatment response than those with no UES abnormality (P = 0.009). Similarly, after controlling for treatment type, those with UES abnormality had 13.9 times greater odds of poor treatment response compared to those with no UES abnormality (P = 0.017). The presence of UES abnormalities in patients with achalasia significantly predicted poorer treatment response as compared to those with normal UES function.

The Medical-Psychiatric Coordinating Physician–Led Model: Team-Based Treatment for Complex Patients

We propose a patient care model involving psychiatrist-led multispecialty teams for treatment of the most treatment-refractory segment of "complex" outpatients. We call the psychiatrist taking this leadership role the Medical-Psychiatric Coordinating Physician. The authors conducted a pilot study for this treatment model with 52 office-based outpatient cases each involving complex patients, and each with at least 2 major treatment failures. They followed these patients empirically for at least 18 months. Outcomes examined included Hamilton Anxiety Rating Scale; Hamilton Depression Rating Scale; and Health Related Quality of Life-14 scores (HRQOL-14, modified), in association with a comprehensive treatment review. Comprehensive treatment review indicated sustained improvement in at least 2 of 4 clinical dimensions (utilization, treatment adherence, symptomatology, and quality of life) in 44 of 52 patients. Included were Hamilton Anxiety Rating Scale scores that improved significantly from 26.27 ± 7.5 to 18.13 ± 5.74 (p < 0.0001) and Hamilton Depression Rating Scale scores that improved from 22.02 ± 7.10 to 14.58 ± 6.46 (p < 0.0001). The Health-Related Quality of Life-14 improved significantly for general health from 2.54 ± 1.03 to 2.12 ± 1.06 (p < 0.0001), and sick days per month from 11.22 ± 7.76 to 6.60 ± 7.51 (p < 0.0001). The Medical-Psychiatric Coordinating Physician-led multispecialty team method may be advantageous for the ongoing outpatient treatment of management-intensive, complex patients. We offer this model as having a place among the available integrated care models for the treatment of comorbid psychiatric-systemic medical illness.

Serotonin syndrome due to fluoxetine and tramadol in renal impaired patient

Serotonin syndrome causes confusion or altered mental status; other symptoms include myoclonus, shivering, tremors, diaphoresis, hyperreflexia, incoordination, fever and diarrhoea. Tramadol possesses dual pharmacological effects i.e., a weak opiate agonist at mu, kappa and delta opiate receptors along with reuptake inhibition of norepinephrine and serotonin. Risk associated with tramadol increases when co-administered with serotonergic antidepressants or MAOIs (monoamine oxidase inhibitors) and in renal impaired. The incidence of this syndrome is less than 1% as most of the cases remain unreported. The case highlights the fact that interaction between serotonergic agents like fluoxetine and tramadol especially in the presence of co-morbid medical illness can lead to serotonin syndrome.

Cognition in Late-Life Depression: Treatment Considerations

Late life depression (LLD) frequently presents with cognitive impairment, and growing evidence suggests that these disease processes are "linked" in multiple ways. For some individuals, LLD may be a recurrence of a long-standing depressive illness, while for others it may be the leading symptom of a developing neuropathological disorder. Overall, studies investigating the relationship between treatment of LLD and improvement in cognitive functioning have yielded mixed results. Research suggests that a subset of individuals with LLD and cognitive dysfunction will experience an improvement in cognitive function after antidepressant treatment, though a significant proportion will continue to exhibit cognitive impairment following resolution of their depressive symptoms. From a treatment standpoint, it is critical to ensure that an individual's depressive symptoms have been treated to remission, measured by a standardized rating scale such as the Geriatric Depression Scale (GDS). SSRI or SNRI monotherapy is often effective, and may be enhanced by employing an evidence-based psychotherapy such as Problem Solving Therapy (PST) or Interpersonal Therapy (IPT), modified to accommodate cognitive impairments that may be present. With respect to specific treatment of cognitive dysfunction, cognitive augmentation or training strategies can be helpful for some patients, and may be explored in combination with treatment of the primary depressive episode. While the introduction of a cholinesterase inhibitor (e.g. donepezil) may be considered, the potential benefit (modest improvement in cognition and functioning) must be weighed against an increased risk for worsening or recurrent depression. Finally, lifestyle factors-such as aerobic exercise, follow-up with a primary care physician for management of co-morbid medical illnesses, and regular participation in stimulating activities (such as through a senior center)-are important and should be included as part of the overall treatment plan.

Psychiatry in primary care using the three-stage assessment

Mental illness imposes a massive burden on all levels of service, including primary care. Challenges particular to primary care include the overwhelming service loads and time/resource constraints. A further challenge revolves around the frequent mismatch between undergraduate teaching and the clinical nature of psychiatric care in primary level clinics. Clinical presentations at primary level are often nonspecific and undifferentiated, and complicated by comorbid medical illness and psychosocial stressors. The three-stage assessment that embraces the core principles of family practice can be adapted to incorporate the psychiatric needs of patients in primary care and deliver a truly holistic and integrated assessment of their individual needs. These adaptations need not involve additional training or the need for additional clinical tasks. Psychiatric management requires continuity of care within an enduring therapeutic relationship, which provides the ideal framework within which a comprehensive assessment and management plan can be formulated. Successful adaptations to the three-stage assessment could provide an effective (and efficient) model for the integration of psychiatry at the primary care level.

Primary or secondary? What came first and how to treat?

Most of the literature regarding the importance of accurately and efficiently differentiating neuropsychiatric symptoms as secondary to medical conditions or as a primary psychiatric illnesses is found in the emergency department setting. It has been reported that 6 to 12% of patients presenting to the emergency department have psychiatric complaints or behavioral disturbances.12 Patients with psychiatric or behavioral disturbances are generally “medically cleared” prior to transfer to psychiatric care.2 Assessing if a patient is “medically cleared” helps to identify medical illnesses that could cause or contribute to psychiatric or behavioral symptoms which may make treatment at a psychiatric facility inappropriate or even dangerous.2 Appropriate treatment in the emergency department setting, therefore, may prevent morbidity and mortality associated with misdiagnosing of a medical illness as a psychiatric illness and from improper treatment of psychiatric illnesses.2 When psychiatric, neurologic, or behavioral manifestations are secondary to medical conditions, the focus of treatment should be on the underlying condition.3 This can be said for any kind of signs or symptoms – rarely is a single or set of signs or symptoms addressed without an evaluation for the underlying root cause. Symptomatic treatment of the neuropsychiatric manifestations, however, should not be overlooked and should run parallel to the primary condition.3To help identify a primary psychiatric illness compared to symptoms secondary to a medical illness, several factors that may assist in clarifying diagnosis include a focus on cognitive versus somatic symptoms, identification of personal or family history of psychiatric illness and response to treatment, careful neurologic exam emphasizing cognitive and mental status exam as part of the physical exam, and an understanding that a psychiatric diagnosis is not purely a diagnosis of exclusion of medical illnesses.3 Features suggesting that psychiatric symptoms are secondary to a medical illness include an abrupt onset with no known or readily recognizable precipitants, a temporal association with onset, worsening, or remission of the psychiatric symptoms concurrent with the medical illness, and the presence of atypical features.34 Additionally, the absence of a personal or family history of psychiatric diagnosis, late onset of new behavioral symptoms, obvious systemic disease, evidence of increased intracranial pressure, nonauditory hallucinations, use of psychoactive or centrally-acting medications, the occurrence of autonomic dysfunction with good premorbid function, and treatment resistance further suggest a medical origin.4 Though routine laboratory testing of all psychiatric patients presenting to the emergency department has not been supported in the literature, it is suggested that a complete history (including a detailed medication history) and physical exam with a full set of vital signs may be sufficient to exclude medical reasons for symptom presentation.125 Further laboratory and ancillary testing may be guided by the obtained information.125 Obtaining information directly from the patient may be, at times, difficult to obtain, therefore, collateral history from bystanders, family, friends, caregivers, health care professionals, law enforcement, paramedics, etc. is important.2Illnesses that may be commonly known to be associated with psychiatric symptoms are presented in Table 1. Increasing awareness and understanding of neuropsychiatric symptoms and adverse effects (and subsequently, management) may lead to more appropriate therapy choices or management and improved patient care. Additionally, comorbid medical illnesses may have implications on psychotropic medication selection. This issue of the Mental Health Clinician highlights psychiatric and neurologic manifestations of medical illnesses or those adverse effects secondary to medications.

A study of psychiatry morbidity and co-morbid physical illness among convicted and awaiting trial inmates in Jos prison

BackgroundHaving a psychiatric diagnosis is still considered a major burden in life. In addition to dealing with stigma regarding mental illness, persons with severe mental illness have an added risk of having co-morbid medical illnesses that can further impair their already turbulent life. The importance of detecting co-morbid medical illnesses is to ensure a holistic treatment. This study assessed the prevalence of psychiatric morbidity and co-morbid physical illness among convicted and awaiting trial inmates in Jos prison. MethodA cross-sectional, descriptive study was carried out among 608 male inmates in Jos maximum security prison, Plateau State, Nigeria. They were screened with self administered GHQ-28 questionnaire and interviewed using CIDI. ResultsMore than half (57%) of the studied subjects had a psychiatric disorder with substance use disorder as the commonest (48.7%) diagnosis. Physical co-morbidity was found in (18%) of the subjects with infectious disease (A00–A99) as the commonest source 13 (3.7%) of physical co-morbidity among the subjects. A statistically significant relationship was found between psychiatric disorder and co-morbid physical illness (p = 0.000). ConclusionThe study showed a high rate of psychiatric morbidity and co-morbid physical illness with infectious disease being the commonest source of physical co-morbidity; and substance use disorder the commonest psychiatric disorder among the prison inmates.

Upper Esophageal Sphincter Abnormalities Are Strongly Predictive of Treatment Response in Patients with Achalasia

Purpose: The introduction of high resolution esophageal manometry (HRM) has allowed the ability to assess the upper esophageal sphincter (UES). However, UES abnormalities are often interpreted as incidental findings with no defined significance. We hypothesized that UES abnormalities have clinical significance and may predict treatment response in patients with achalasia. Methods: We performed a retrospective study of 41 consecutive patients referred for HRM with a final manometric diagnosis of achalasia. Patients were sub-divided by presence or absence of UES abnormality, and clinical and manometric profiles were compared. Correlation between UES abnormality and sub-type (i.e. hypertensive, hypotensive or impaired relaxation) and a number of variables, including qualitative treatment response, achalasia sub-type, co-morbid medical illness, psychiatric illness, surgical history, dominant presenting symptom, treatment type, age, and gender were also evaluated. Results: Among all 41 patients, 24 (58.54%) had a UES abnormality present. There were no significant differences between the groups in terms of age, gender or any other clinical or demographic profi les. Among those with UES abnormalities, the majority were either hypertensive (41.67%) or had impaired relaxation (37.5%), as compared to hypotensive (20.83%), although this did not reach statistical significance (p=0.42). There was no specific association between treatment response and treatment type received; however, there was a significant association between UES abnormalities and treatment response. In patients with achalasia and concomitant UES abnormalities, 87.5% had poor treatment response, while only 12.5% had favorable response. In contrast, in patients with achalasia and no UES abnormalities, the majority (78.57%) had good treatment response, as compared to 21.43% with poor treatment response (p=0.0001). After controlling for achalasia sub-type, those with UES abnormality had 26 times greater odds of poor treatment response than those with no UES abnormality (p = 0.009). Similarly, after controlling for treatment type, those with UES abnormality had 13.9 times greater odds of poor treatment response compared to those with no UES abnormality (p=0.017). Conclusion: The presence of UES abnormalities in patients with achalasia significantly predicted poorer treatment response as compared to those with normal UES function, irrespective of the type of treatment received or achalasia sub-type. Future prospective studies are needed to determine whether specific UES abnormalities have additional prognostic value and to further delineate the underlying mechanism between UES dysfunction with achalasia in order to optimize therapeutic treatment modalities.

Acute Hemodilution is Safe in Patients with Comorbid Illness Undergoing Partial Hepatectomy

Despite increased use of acute hemodilution (AH) to reduce perioperative blood transfusion in patients undergoing partial hepatectomy, there is a lack of data on safety in those with comorbid medical illness. We performed a retrospective review of 96 patients undergoing partial hepatectomy with AH and low central venous pressure (CVP) anesthesia. The cohort was compared with 63 patients undergoing partial hepatectomy using standard anesthetic management (SA) and low CVP anesthesia. All were American Society of Anesthesiologists physical status 3 or 4. 58 per cent were baseline hypertensive on medication. Hepatic resection was predominantly performed for metastatic colorectal (41%) and primary hepatic (32%) cancer. Forty per cent underwent major hepatectomy. The mean volume of blood removed for AH was 497 mL (range, 0 to 1 L). Most achieved low CVP (AH 90% vs SA 84%, P = 0.3). Blood loss was lower with AH (mean 480 mL vs 904 mL, P < 0.001). Blood transfusion rate was 74 per cent lower with AH (P < 0.001). There was no difference in cardiac, respiratory, renal, or overall complications with AH compared with SA. Acute hemodilution is well tolerated by patients with comorbid illness undergoing partial hepatectomy, favoring ongoing use and further study.

Predictors and Adverse Pregnancy Outcomes Associated with Antepartum Discharge Against Medical Advice

To determine predictors and pregnancy outcomes associated with antepartum discharge against medical advice (AMA D/C). Retrospective cohort study of state-level maternal and infant hospital discharge data linked to vital statistics data for antepartum admissions in California from 1995 to 2005. (N = 203,250). After adjusting for comorbid conditions, the odds of AMA D/C for Black women were twice that of white women (OR = 2.00, 95% CI 1.70-2.35). Publicly insured women had 3.5 times the odds of AMA D/C compared to privately insured women (OR = 3.54, 95% CI 3.02-4.15). AMA D/C was also higher among substance abusers and women with mental illness (OR = 1.96, 95% CI 1.43-2.67 and OR = 4.45, 95% CI 3.81-5.21 respectively). Most notably, AMA D/C tripled the odds of fetal death in patients admitted for pregnancy-induced hypertension (OR = 3.08, 95% CI 1.36-6.98) and increased the odds of neonatal morbidity (respiratory distress syndrome OR = 1.35, 95% CI 1.07-1.70 and small-for-gestational-age OR = 1.47, 95% CI 1.15-1.89) in patients admitted with preterm premature rupture of membranes. Vulnerable populations and patients with comorbid medical and mental illnesses are at increased risk for AMA D/C and its associated adverse pregnancy outcomes. Targeted interventions and resources to support at-risk populations are needed.

Cross-sectional study of the characteristics, healthcare usage, morbidity and mortality of injecting drug users attending an inner city emergency department

BackgroundThe affliction of injecting drug use (IDU) has resulted in the emergence of a subgroup of people with a unique set of medical issues. We aimed to describe the emergency...

Management of Human Immunodeficiency Virus Infection in Advanced Age

Human immunodeficiency virus (HIV)-positive patients treated with antiretroviral therapy now have increased life expectancy and develop chronic illnesses that are often seen in older HIV-negative patients. To address emerging issues related to aging with HIV. Screening older adults for HIV, diagnosis of concomitant diseases, management of multiple comorbid medical illnesses, social isolation, polypharmacy, and factors associated with end-of-life care are reviewed. Published guidelines and consensus statements were reviewed. PubMed and PsycINFO were searched between January 2000 and February 2013. Articles not appearing in the search that were referenced by reviewed articles were also evaluated. The population of older HIV-positive patients is rapidly expanding. It is estimated that by 2015 one-half of the individuals in the United States with HIV will be older than age 50. Older HIV-infected patients are prone to having similar chronic diseases as their HIV-negative counterparts, as well as illnesses associated with co-infections. Medical treatments associated with these conditions, when added to an antiretroviral regimen, increase risk for polypharmacy. Care of aging HIV-infected patients involves a need to balance a number of concurrent comorbid medical conditions. HIV is no longer a fatal disease. Management of multiple comorbid diseases is a common feature associated with longer life expectancy in HIV-positive patients. There is a need to better understand how to optimize the care of these patients.

Evaluation of the Cardiac Depression Visual Analogue Scale in a medical and non-medical sample

Comorbid depression and medical illness is associated with a number of adverse health outcomes such as lower medication adherence and higher rates of subsequent mortality. Reliable and valid psychological measures capable of detecting a range of depressive symptoms found in medical settings are needed. The Cardiac Depression Visual Analogue Scale (CDVAS) is a recently developed, brief six-item measure originally designed to assess the range and severity of depressive symptoms within a cardiac population. The current study aimed to further investigate the psychometric properties of the CDVAS in a general and medical sample. The sample consisted of 117 participants, whose mean age was 40.0 years (SD = 19.0, range 18–84). Participants completed the CDVAS, the Cardiac Depression Scale (CDS), the Depression Anxiety Stress Scales (DASS) and a demographic and health questionnaire. The CDVAS was found to have adequate internal reliability (α = .76), strong concurrent validity with the CDS (r = .89) and the depression sub-scale of the DASS (r = .70), strong discriminant validity and strong predictive validity. The principal components analysis revealed that the CDVAS measured only one component, providing further support for the construct validity of the scale. Results of the current study indicate that the CDVAS is a short, simple, valid and reliable measure of depressive symptoms suitable for use in a general and medical sample.

General medical burden in bipolar disorder: findings from the LiTMUS comparative effectiveness trial

This study examined general medical illnesses and their association with clinical features of bipolar disorder. Data were cross-sectional and derived from the Lithium Treatment - Moderate Dose Use Study (LiTMUS), which randomized symptomatic adults (n = 264 with available medical comorbidity scores) with bipolar disorder to moderate doses of lithium plus optimized treatment (OPT) or to OPT alone. Clinically significant high and low medical comorbidity burden were defined as a Cumulative Illness Rating Scale (CIRS) score ≥4 and <4 respectively. The baseline prevalence of significant medical comorbidity was 53% (n = 139). Patients with high medical burden were more likely to present in a major depressive episode (P = .04), meet criteria for obsessive-compulsive disorder (P = .02), and experience a greater number of lifetime mood episodes (P = 0.02). They were also more likely to be prescribed a greater number of psychotropic medications (P = .002). Sixty-nine per cent of the sample was overweight or obese as defined by body mass index (BMI), with African Americans representing the racial group with the highest proportion of stage II obesity (BMI ≥35; 31%, n = 14). The burden of comorbid medical illnesses was high in this generalizable sample of treatment-seeking patients and appears associated with worsened course of illness and psychotropic medication patterns.

Ethics Commentary: Ethical Issues in Geriatric Psychiatry

By 2030, due to the aging of the baby boomers, the U.S. Census Bureau predicts that nearly one in five people will be 65 or older—a substantial increase from the 13% of the population that was 65 or older in 2010. This population of older adults is projected to have increased needs for mental health care, which the current workforce is inadequate to meet (1, 2). For example, by the year 2050, an estimated 13 million adults will suffer from Alzheimer’s disease (AD) (3). Many of these individuals will develop behavioral and psychological symptoms as their disease progresses. Depressive disorders remain underdetected in older adults, and despite years of attention to the issue of undertreatment of depression in the older adult population, this continues to be a problem (1, 4). Ongoing stigma about mental health treatment on the part of patients, as well as misconceptions and inadequate training regarding depression on the part of health care providers, likely contribute to the lack of identification and treatment of depressive disorders in older adults (5). Thus, although many older adults will age “successfully,” with intact cognition and stable mental health, a substantial minority will experience new onset psychiatric disorders, recurrence of disorders that initially developed earlier in life, or psychiatric manifestations of neurologic and medical disorders and their treatment. Special ethical challenges emerge at the intersection of aging, comorbidmedical illnesses, and psychiatric illnesses. Although a complete discussion of these issues is beyond the scope of this column, two topics that have received relatively little attention in the literature—financial exploitation and ethical issues in hospice care for patients with psychiatric disorders—will be discussed through the use of case examples.

Frequent Emergency Department Use Among Released Prisoners With Human Immunodeficiency Virus: Characterization Including a Novel Multimorbidity Index

The objective was to characterize the medical, social, and psychiatric correlates of frequent emergency department (ED) use among released prisoners with human immunodeficiency virus (HIV). Data on all ED visits by 151 released prisoners with HIV on antiretroviral therapy (ART) were prospectively collected for 12 months. Correlates of frequent ED use, defined as having two or more ED visits postrelease, were described using univariate and multivariate models and generated medical, psychiatric, and social multimorbidity indices. Forty-four (29%) of the 151 participants were defined as frequent ED users, accounting for 81% of the 227 ED visits. Frequent ED users were more likely than infrequent or nonusers to be female; have chronic medical illnesses that included seizures, asthma, and migraines; and have worse physical health-related quality of life (HRQoL). In multivariate Poisson regression models, frequent ED use was associated with lower physical HRQoL (odds ratio [OR] = 0.95, p = 0.02) and having not had prerelease discharge planning (OR = 3.16, p = 0.04). Frequent ED use was positively correlated with increasing psychiatric multimorbidity index values. Among released prisoners with HIV, frequent ED use is driven primarily by extensive comorbid medical and psychiatric illness. Frequent ED users were also less likely to have received prerelease discharge planning, suggesting missed opportunities for seamless linkages to care.

Perceived Stress and Comorbid Illness Predict Depressive Symptomatology in People with Coeliac Disease

A high prevalence of depression is found in people with coeliac disease (CD). People with CD who are depressed are less likely to manage their illness effectively, which may lead to complications. Identification of variables associated with depression in people with CD may facilitate early detection and intervention. Participants were 749 members (125 males, 622 females) of the Queensland Coeliac Society (aged 18–88 years), recruited via a mailout. Participants completed the Modified Zung Self‐Rating Depression Scale, the Perceived Stress Scale, and the Perceived Consequences Subscale (from the Revised Illness Perception Questionnaire). Stress (p = .001) and comorbid medical illness (p = .01) were significantly associated with depression in CD. The current study made an original contribution to the body of literature by identifying stress and comorbid medical illness as predictors of depression in CD.

Dysregulated relationship of inflammation and oxidative stress in major depression

Chronic inflammation and oxidative stress have been implicated in the pathophysiology of Major Depressive Disorder (MDD), as well as in a number of chronic medical conditions. The aim of this study was to examine the relationship between peripheral inflammatory and oxidative stress markers in un-medicated subjects with MDD compared to non-depressed healthy controls and compared to subjects with MDD after antidepressant treatment. We examined the relationships between IL-6, IL-10, and the IL-6/IL-10 inflammatory ratio vs. F2-isoprostanes (F2-IsoP), a marker of oxidative stress, in un-medicated MDD patients (n=20) before and after 8 weeks of open-label sertraline treatment (n=17), compared to healthy non-depressed controls (n=20). Among the un-medicated MDD subjects, F2-IsoP concentrations were positively correlated with IL-6 concentrations (p<0.05) and were negatively correlated with IL-10 concentrations (p<0.01). Accordingly, F2-IsoP concentrations were positively correlated with the ratio of IL-6/IL-10 (p<0.01). In contrast, in the control group, there were no significant correlations between F2-IsoPs and either cytokine or their ratio. After MDD subjects were treated with sertraline for 8 weeks, F2-IsoPs were no longer significantly correlated with IL-6, IL-10 or the IL-6/IL-10 ratio. These data suggest oxidative stress and inflammatory processes are positively associated in untreated MDD. Our findings are consistent with the hypothesis that the homeostatic buffering mechanisms regulating oxidation and inflammation in healthy individuals become dysregulated in untreated MDD, and may be improved with antidepressant treatment. These findings may help explain the increased risk of comorbid medical illnesses in MDD.

Update on bloodstream infections in ICUs

To describe new developments in the epidemiology and outcomes associated with bloodstream infections (BSIs) in ICUs. The incidence and outcomes associated with BSI among patients admitted to ICUs have been changing as a result of increasing numbers of older patients with comorbid medical illnesses suffering critical illness. Community-onset healthcare-associated BSIs are recognized as important causes of BSIs in ICUs and are distinct from community-acquired and nosocomial BSIs. Electronic surveillance systems are evolving that provide efficient information about the occurrence of BSIs and for tracking the emergence of resistance. The incidence of healthcare-associated BSIs increases and is associated with bacteria resistant to antimicrobials used in community-acquired infections. The recent years have witnessed the emergence of extensively resistant bacteria in many regions worldwide, and this is associated with major implications for failure of antimicrobial therapies. Enhanced preventive efforts and optimization of therapy are needed in order to reduce the major burden of BSIs in critically ill patients and to minimize the further emergence of resistance.