Prevalence of neurocognitive dysfunction and other clinical manifestations in disabled patients with systemic lupus erythematosus

OBJECTIVE: While work disability is common in patients with systemic lupus erythematosus (SLE), it is not known which lupus disease characteristics predispose toward work disability. We examined demographic, clinical, serological, and neuropsychological factors in a group of disabled and nondisabled patients with SLE. METHODS: Fifty patients meeting American College of Rheumatology criteria for SLE were assessed for work status, disease characteristics, fatigue, anxiety, depressive symptoms, and quality of life. All subjects underwent an abbreviated panel of neuropsychological tests. Subjects who had formal work disability (social security or longterm disability, n = 16) and subjects who self-reported work disability without formal recognition (n = 8) were compared to subjects denying work disability from lupus (n = 26). RESULTS: Education level, African-American race, and SLICC Damage Index score were significantly associated with formal work disability relative to other subjects. Neurocognitive impairment (OR 14.44, 95% CI 3.01, 68.20; p = 0.001), nephritis (OR 3.75, 95% CI 1.01, 13.9; p = 0.048), and discoid lupus (OR 19.93, 95% CI 3.51, 113.3; p = 0.001) were all associated with formal disability. Formally disabled patients had higher fatigue and anxiety scores and more impaired quality of life in many domains relative to nondisabled subjects. Subjects with self-reported work disability also had neurocognitive dysfunction, high fatigue scores, and poor quality of life, but in other respects appeared to have milder disease than formally disabled subjects. CONCLUSION: Neurocognitive dysfunction and fatigue are 2 manifestations that may contribute materially to work disability in lupus. Other associated factors include low education levels, SLICC Damage Index scores, discoid lupus, nephritis, and possibly African-American race.     

eNOS gene therapy exacerbates hepatic ischemia-reperfusion injury in diabetes: a role for eNOS uncoupling

Previous studies indicate that endothelial nitric oxide synthase (eNOS) function is impaired in diabetes as a result of increased vascular generation of reactive oxygen species. We hypothesized that eNOS gene therapy would augment NO. bioavailability and protect against hepatic ischemia-reperfusion (I-R) injury in type 2 diabetes mellitus. We developed a transgenic (Tg) diabetic mouse in which eNOS is systemically overexpressed. We also examined the effects of hepatic eNOS adenovirus therapy in diabetic mice. Diabetic (db/db) and nondiabetic mice were subjected to hepatic I-R injury. In nondiabetic mice, genetic overexpression of eNOS (both eNOS-Tg and eNOS adenovirus) resulted in hepatoprotection. In contrast, hepatic I-R injury was significantly increased in the db/db eNOS-Tg mouse, as serum alanine aminotransaminase (ALT) levels were increased by 3.3-fold compared with diabetic controls. Similarly, eNOS adenovirus treatment resulted in a 3.2-fold increase in serum ALT levels as compared with diabetic controls. We determined that hepatic eNOS was dysfunctional in the db/db mouse and increased genetic expression of eNOS resulted in greater production of peroxynitrite. Treatment with the eNOS cofactor tetrahydrobiopterin (BH4) or the BH4 precursor sepiapterin resulted in a significant decrease in serum ALT levels following I-R injury. We present clear examples of the protective and injurious nature of NO. therapy in I-R. Our data indicate that eNOS exists in an "uncoupled" state in the setting of diabetes and that "recoupling" of the eNOS enzyme with cofactor therapy is beneficial.     

Topotecan and vincristine combination is effective against advanced bilateral intraocular retinoblastoma and has manageable toxicity

BACKGROUND:

New, effective chemotherapeutic agents are needed for intraocular retinoblastoma.

METHODS:

This institutional clinical trial sought to estimate the rate of response to 2 courses of vincristine and topotecan (VT) window therapy in patients with bilateral retinoblastoma and advanced disease (Reese‐Ellsworth group IV or V) in at least 1 eye. The topotecan dose started at 3 mg/m²/day for 5 days and was adjusted to target a systemic exposure of 140 ± 20 ng/mL · hour. The vincristine dose was 0.05 mg/kg for patients <12 months of age and 1.5 mg/m² for those >12 months of age at diagnosis.

RESULTS:

From February 2005 to June 2010, 27 patients received VT window therapy. Median age at enrollment was 8.1 months (range, 0.7‐22.1 months). Twenty‐four patients (88.9%) responded to window therapy (95% confidence interval = 71.3%‐96.9%). Hematologic toxicity comprised grade 4 neutropenia (n = 27), grade 3 anemia (n = 19), and grade 3/4 thrombocytopenia (n = 16). Thirteen patients had grade 3 nonhematologic toxicity. Granulocyte colony‐stimulating factor support was added after 10 patients had been treated, and it significantly reduced the duration of grade 4 neutropenia (median, 7 vs 24 days; P < .001). Pharmacokinetic studies showed rapid changes in topotecan clearance rates during the first year of life.

CONCLUSIONS:

The combination of topotecan and vincristine is effective for the treatment of advanced intraocular retinoblastoma. Granulocyte colony‐stimulating factor treatment alleviates the duration of grade 4 neutropenia. Appropriate topotecan starting doses for patients 0‐3, 3‐6, 6‐9, 9‐12, and >12 months of age are specified. Cancer 2012. © 2012 American Cancer Society.     

Colon Cancer Perforation Presenting as a Strangulating Ventral Hernia

Colorectal cancer remains the second leading cause of death from malignant disease. Despite improvements in the treatment modalities offered to patients, more than half of the operated patients die from the disease. The most common presenting symptoms of colonic carcinoma are changes in bowel habits, bleeding, abdominal pain, abdominal mass, stools mixed with mucus or not, weight loss, anorexia, and other characteristics related to metastasis. Here, the case of a 74-year-old female patient with colon cancer perforation presenting as a strangulating ventral hernia and a mini-review of the current literature are presented.Key words: Colon cancer, Unusual presentation of cancer, Perforation     

Implementation of a multidisciplinary treatment team for hepatocellular cancer at a Veterans Affairs Medical Center improves survival

Several methods of treatment for hepatocellular carcinoma (HCC) are often used in combination for either palliation or cure. We established a multidisciplinary treatment team (MDTT) at the San Francisco Veterans Affairs Medical Center in November 2003 and assessed whether aggressive multimodality treatment strategies may affect survival. A prospective database was established and follow-up information from patients with presumed HCC was collected up to November 2006. Information from the American College of Surgeons (ACS) cancer registry from January 2000 to November 2003 identified patients with HCC that were evaluated at the same institution prior to the establishment of the MDTT. The establishment of a MDTT resulted in the doubling of patient referrals for treatment. Significantly more patients were evaluated at earlier stages of disease and received either palliative or curative therapies. The overall survival (p<0.0001) and length of follow-up (p<0.05) were significantly improved after the establishment of the MDTT. Stage-by-stage comparisons indicate that aggressive multimodality therapy conferred significant survival advantage to patients with American Joint Commission on Cancer (AJCC) stage II HCC (odds ratio 15.50, p<0.001). Multidisciplinary collaboration and multimodality treatment approaches are important in the management of hepatocelluar carcinoma and improves patient survival.     

Evaluating the Effectiveness of Dispatch-assisted Cardiopulmonary Resuscitation Instructions

Objectives: To determine the frequency of agonal breathing during cardiac arrest (CA), its impact on the ability of 9‐1‐1 dispatchers to identify CA, and the impact of dispatch‐assisted cardiopulmonary resuscitation (CPR) instructions on bystander CPR rates. Methods: A before‐after observational study enrolling out‐of‐hospital adult CA patients where resuscitation was attempted in a single city with basic life support with defibrillation/advanced life support tiered emergency medical services. Victim, caller, and system characteristics were measured during two successive nine‐month periods before (control group) and after (intervention group) the introduction of dispatch‐assisted CPR instructions. Results: There were 529 CAs between July 1, 2003, and December 31, 2004. Victim characteristics were similar in the control (n= 295) and intervention (n= 234) period; mean age was 68.3 years; 66.7% were male; 50.1% of CAs were witnessed; call‐to‐vehicle stop was 6 minutes, 37 seconds; ventricular fibrillation/ventricular tachycardia occurred in 29.9%; and the survival rate was 4.0%. Dispatchers identified 56.3% (95% confidence interval [CI] = 48.9% to 63.0%) of CA cases; agonal breathing was present in 37.0% (95% CI = 30.1% to 43.9%) of all CA cases and accounted for 50.0% (95% CI = 39.1% to 60.9%) of missed diagnoses. Callers provided ventilations in 17.2% and chest compressions in 8.3% of cases as a result of the intervention. Long time intervals were observed between call to diagnosis (2 minutes, 38 seconds) and during ventilation instructions (2 minutes, 5 seconds). Bystander CPR rates increased from 16.7% in the control phase to 26.4% in the intervention phase (absolute rate, 9.7%; 95% CI = 8.5% to 11.3%; p = 0.006). Conclusions: This trial demonstrates an increase in bystander CPR rate after the introduction of dispatch‐assisted CPR. Agonal breathing occurred frequently and had a negative impact on the recognition of CA. There were long time intervals between call initiation and diagnosis of CA and during mouth‐to‐mouth ventilation instructions.     

Lymphedema: A primer on the identification and management of a chronic condition in oncologic treatment

The primary goals of oncologic therapy are the compassionate care of cancer patients, eradication of disease, and palliation of symptoms. Advances in various targeted therapies such as highly conformal and image‐guided radiotherapy techniques, sentinel lymph node dissection, and molecularly targeted agents hold the promise of allowing those goals to be reached with fewer treatment‐related complications. Unfortunately, certain side effects remain problematic due to the inability to completely avoid injuring normal tissues. Lymphedema, a chronic condition that occurs as a result of the body's inability to drain lymph fluid from the tissues, is a common treatment‐related side effect experienced by cancer patients. In this review, many of the important aspects of lymphedema with which clinicians who treat cancer patients should be familiar are outlined, including the anatomy, pathophysiology, diagnosis, and management of this condition. The authors also identify some of the resources available both to cancer patients with lymphedema and to the clinicians who treat them. It is hoped that this review will convey the importance of the early identification and management of this incurable disorder because this is essential to minimizing its complications. CA Cancer J Clin 2009;59:8–24. © 2009 American Cancer Society.     

Nursing staff attitudes and behaviours regarding family presence in the hospital setting

Title. Nursing staff attitudes and behaviours regarding family presence in the hospital setting. Aim. This paper is a report of a study conducted to assess the attitudes and values of nursing staff towards family presence during routine nursing care. Background. Nursing staff attitudes are an important factor in the adoption of family‐centred care for children, and for all ages in the emergency room, special care units, and anaesthesia induction and recovery. Little is documented about nurse attitudes and behaviours related to family presence during day‐to‐day routine nursing care. Method. In 2006, primary data were collected with a convenience sample of 89 nursing staff using an 18‐item questionnaire developed by the authors and based on several family‐centred care instruments in the literature. Items assessed attitude and nurse behaviours related to family presence during routine nursing care. Findings. Nurses’ attitudes and behaviours towards family presence during routine nursing care were generally favourable. There was low agreement about family members being allowed to visit whenever the patient wished. Nursing staff attitudes were consistent with their self‐reported behaviours supporting family presence. Conclusion. Nursing staff who believe family presence is important are more likely to include families in daily care. The organization plays a key role in encouraging family‐centred care by providing appropriate education and support to nursing staff.