Working Memory and Language Relate to Report of Socio-Emotional Functioning in Children with Hearing Loss.

Background: Children with hearing loss have been found to have significantly more behavioral and emotional challenges than their typically hearing peers, though these outcomes are variable at the individual level. Working memory deficits have been found to relate to executive functioning and overall emotion regulation, leading to behavior challenges. Language development is essential for development of social relationships and communicating one's needs and this may lead to distress when children cannot communicate effectively. Based on prior findings in children with hearing loss and their typically hearing peers, working memory and language skills were hypothesized to be related to parent and teacher report of socio-emotional functioning. Methods: Participants were 35 children with hearing loss (66% female, M = 5.17 years old, SD = ±1.97) whose language, working memory, and socio-emotional functioning were evaluated during the course of treatment and educational planning. Results: Bivariate analyses indicated that working memory was related to a number of socio-emotional domains (e.g., functional communication, atypicality, withdrawal), as were language scores (e.g., social skills, inattention). The direction of these associations was such that stronger working memory and language skills were related to more regulated socio-emotional functioning. Conclusions: This study is limited in generalizability by size and the relative homogeneity of the sample. A call to action of the current study includes more education with regard to profiles and presentations of children with hearing loss, and an early focus on socio-emotional learning to foster the development of regulatory skills.

Management of adverse events associated with the use of everolimus in patients with advanced renal cell carcinoma.

PURPOSE: In April 2009, an expert group of 11 physicians and clinical nurses met to discuss the management of selected adverse events associated with the use of everolimus for the treatment of metastatic renal cell carcinoma (mRCC). Everolimus is an orally administered inhibitor of the mammalian target of rapamycin that recently received approval from the European Medicines Agency for the treatment of advanced RCC that has progressed on or after treatment with vascular endothelial growth factor (VEGF)-targeted therapy, and from the United States Food and Drug Administration for treatment of advanced RCC after failure of sorafenib or sunitinib. Before the approval of everolimus, no standard therapy existed for the treatment of mRCC after failure of VEGF-targeted therapy. RECORD-1 (Renal Cell cancer treatment with Oral RAD001 given Daily) was the pivotal multicenter, phase III, randomised, double-blind, placebo-controlled trial of everolimus that led to approval for patients with disease progression on or after treatment with VEGF-targeted agents. Safety data from RECORD-1 were reviewed by these clinicians, all of whom had experience using everolimus in patients with mRCC. Adverse events discussed were non-infectious pneumonitis, infections, stomatitis and metabolic abnormalities. RESULTS: The outcome of this discussion is summarised here. Guidance for management of these adverse events is provided. Both clinicians and patients should be aware of the potential side-effects of everolimus and understand that these side-effects are manageable with standard care to optimise patient benefit.

Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma.

RATIONALE: Noninfectious pneumonitis is a known class effect of mammalian target of rapamycin (mTOR) inhibitors. OBJECTIVES: To assess the incidence, radiographic patterns, management, and outcome of pneumonitis in patients with advanced renal cell carcinoma receiving everolimus. METHODS: Clinical study data from 416 patients, randomized to receive everolimus versus placebo, were analyzed for adverse events of pneumonitis. Radiographic studies performed every 8 weeks were subject to a prospective, independent, blinded central review for the presence of findings indicative of pneumonitis. MEASUREMENTS AND MAIN RESULTS: Of 274 patients receiving everolimus, clinical pneumonitis was suspected for 37 patients (13.5%) (none with placebo). Nine cases (3.3%) were grade 1 (asymptomatic), 18 (6.6%) were grade 2 (not interfering with daily living), and 10 (3.6%) were grade 3 (interfering with daily living or oxygen indicated). No grade 4 (life-threatening) pneumonitis was observed. Of the 10 patients with grade 3 pneumonitis, 5 had baseline radiological evidence of pneumonitis before everolimus therapy. Twenty of the 37 cases (54.0%) were reversible within the follow-up period; resolution followed dose reduction for 20 patients and treatment discontinuation in 10 patients. Corticosteroid therapy was initiated in 16 cases. Dedicated radiological review of available serial radiographic studies (245 patients receiving everolimus and 132 receiving placebo) found a higher percentage of new radiographic findings even in patients without a diagnosis of clinical pneumonitis who were receiving everolimus versus placebo (38.9 vs. 15.2%). CONCLUSIONS: Early recognition, prompt intervention, and a conservative approach are important in managing the risk associated with noninfectious pneumonitis in association with everolimus. Clinical trial registered with www.clinicaltrials.gov (NCT 00410124).

Characterization of pneumonitis in patients with advanced non-small cell lung cancer treated with everolimus (RAD001).

PURPOSE: To assess the incidence and radiographic and clinical presentation of pneumonitis associated with the mammalian target of rapamycin inhibitor everolimus in patients with advanced non-small cell lung cancer. PATIENTS AND METHODS: A retrospective, centralized review of serial computed tomography scans and corresponding clinical data from patients with advanced non-small cell lung cancer treated with 10-mg oral once daily everolimus monotherapy in a phase II clinical study was conducted. Serial chest CT scans underwent a consensus read by two radiologists for presence of pneumonitis. These cases were then reviewed with corresponding clinical data by a pulmonologist to assess the suspected causality to everolimus and outcome. RESULTS: Twenty-four of 64 patients reviewed were found to have radiographic evidence of pneumonitis. In 16 of these 24 patients, pneumonitis was suspected as either possibly (12) or probably (4) related to everolimus. The most common radiographic manifestations were focal areas of consolidation at the lung bases or ground-glass opacities. Pneumonitis evaluated with Common Terminology Criteria for Adverse Events (version 3) was grade 1 or 2 in 12 of 16 suspected cases, with 4 patients experiencing higher grades. In most of the patients, pneumonitis remained at the same or lower grade without discontinuation of therapy. Patients with evidence of interstitial lung disease at baseline had an increased risk of Common Terminology Criteria for Adverse Events grade more than or equal to 3 pneumonitis. CONCLUSION: Within the limitation of this retrospective study, results suggest that a mostly low-grade pneumonitis with a possible or probable relationship to everolimus was relatively frequent, occurring in 25% of evaluated patients. These results suggest a need for monitoring of pulmonary adverse events and the development of guidelines for managing pneumonitis in future studies with everolimus.

Pulmonary toxicity associated with erlotinib.

Interstitial lung disease (ILD) related to therapy with the drug gefitinib has been well reported. The adverse pulmonary effects of erlotinib are less well known. We report a case of fatal pulmonary toxicity in a patient with advanced non-small cell lung cancer who received erlotinib. He had been found to have pathologic findings of usual interstitial pneumonia (UIP) on the resected lung cancer specimen prior to receiving erlotinib. This case and other published evidence should alert physicians to the possibility of fatal erlotinib-induced ILD. Similar to reports in patients receiving gefitinib, those with pathologic findings of UIP on resected lung specimens or known pulmonary fibrosis may be at particular risk for erlotinib pulmonary toxicity.

Phase I study of inhaled Doxorubicin for patients with metastatic tumors to the lungs.

PURPOSE: To evaluate the toxicity profile of inhalational doxorubicin in patients with malignant disease in the lung. EXPERIMENTAL DESIGN: The OncoMyst Model CDD-2a inhalation device aerosolizes compounds to particles of 2 to 3 mum and prevents exhaled aerosol from escaping into the environment. Deposition efficiency of inhaled Technetium 99m was used to predict deposition of doxorubicin and calculate dose. Treatment was repeated every 3 weeks. No more than moderate pulmonary dysfunction was permitted (forced expiratory volume in 1 s, forced vital capacity, and diffusing capacity for carbon monoxide, all >50% predicted; resting SaO(2) >90%). RESULTS: Fifty-three patients were enrolled at 13 dose levels ranging from 0.4 to 9.4 mg/m(2). The most common histologic diagnoses were sarcoma (n = 19) and non-small cell lung cancer (n = 16). Dose-limiting toxicity (DLT) was observed at the 9.4 mg/m(2) dose level when two of four patients experienced pulmonary DLT. Of 11 patients treated at the 7.5 mg/m(2) dose level, only one showed DLT consisting of a decline in forced vital capacity of >20% from baseline. No significant systemic drug-related toxicity was observed. Several patients experienced declines in pulmonary function test variables, which were attributed to progressive disease. Observed activity included a partial response in a patient with metastatic soft tissue sarcoma previously treated with i.v. doxorubicin and ifosfamide. CONCLUSIONS: Inhaled doxorubicin is safe up to a dose of 7.5 mg/m(2) every 3 weeks in patients with cancer who had normal to moderately impaired pulmonary function.

Aspergillus pulmonary infections in transplant recipients.

Aspergillus infections are increasing in frequency in those undergoing solid organ and hematopoietic stem cell transplantation. The ongoing impact of Aspergillus infection on morbidity and mortality after transplantation makes this subject an area of intense clinical and research interest. This article discusses the evolving epidemiologic features of the infection and its management and diagnosis.

Smoking and timing of cessation: impact on pulmonary complications after thoracotomy.

STUDY OBJECTIVE: The benefit of smoking cessation just prior to surgery in preventing postoperative pulmonary complications has not been proven. Some studies actually show a paradoxical increase in complications in those quitting smoking only a few weeks or days prior to surgery. We studied the effect of smoking and the timing of smoking cessation on postoperative pulmonary complications in patients undergoing thoracotomy. DESIGN AND SETTING: Prospective study conducted in a tertiary care cancer center in 300 consecutive patients with primary lung cancer or metastatic cancer to the lung who were undergoing anatomical lung resection. RESULTS: The groups studied were nonsmokers (21%), past quitters of > 2 months duration (62%), recent quitters of < 2 months duration (13%), and ongoing smokers (4%). Overall pulmonary complications occurred in 8%, 19%, 23%, and 23% of these groups, respectively, with a significant difference between nonsmokers and all smokers (p = 0.03) but no difference among the subgroups of smokers (p = 0.76). The risk of pneumonia was significantly lower in nonsmokers (3%) compared to all smokers (average, 11%; p < 0.05), with no difference detected among subgroups of smokers (p = 0.17). Comparing recent quitters and ongoing smokers, no differences in pulmonary complications or pneumonia were found (p = 0.67). Independent risk factors for pulmonary complications were a lower diffusing capacity of the lung for carbon monoxide (Dlco) [odds ratio [ OR] per 10% decrement, 1.41; 95% confidence interval [ CI], 1.17 to 1.70; p = 0.01) and primary lung cancer rather than metastatic disease (OR, 3.94; 95% CI, 1.34 to 11.59; p = 0.003). Among smokers, a lower Dlco percent predicted (OR per 10% decrement, 1.42; 95% CI, 1.16 to 1.75; p = 0.008) and a smoking history of > 60 pack-years (OR, 2.54; 95% CI, 1.28 to 5.04; p = 0.0008) were independently associated with overall pulmonary complications. CONCLUSIONS: In patients undergoing thoracotomy for primary or secondary lung tumors, there is no evidence of a paradoxical increase in pulmonary complications among those who quit smoking within 2 months of undergoing surgery. Smoking cessation can safely be encouraged prior to surgery.

Thoracentesis in patients with hematologic malignancy: yield and safety.

BACKGROUND: Pleural effusions occur in patients with hematologic malignancies, particularly during periods of hospitalization. Thoracentesis is often performed to diagnose infection and to exclude the presence of complicated parapneumonic effusions. The efficacy and safety of thoracentesis in this setting has not been well-studied. DESIGN: Retrospective chart review of hospitalized patients with hematologic malignancies undergoing thoracentesis. The aim of this study was to assess the role of thoracentesis in establishing a diagnosis of infection in this population and to determine the risk of complications. RESULTS: A total of 100 thoracentesis findings were analyzed in patients with lymphoma (52 patients) and leukemia (27 patients), and in patients who had undergone bone marrow or stem cell transplantation (21 patients). The indication for performing thoracentesis was to exclude infection in 69% of cases. Fever was present in 59% of the patients, and a concomitant lung parenchymal abnormality was present in 69% of cases. Effusions were moderate to large in size (87% of cases), and were both bilateral (62%) and unilateral (38%). Exudates were documented in 83%of the cases. A specific diagnosis was found in 21 patients and was more frequently established in those with lymphoma (31%) compared to the other groups of patients. Diagnoses found included malignancy in 14 cases, chylous effusions in 6 cases, and infection in 1 case. The one patient in whom empyema was found required drainage. The criteria for a parapneumonic effusion were not found in any other patients. The complication rate of 9% (pneumothorax, seven patients; hemothorax, two patients) was comparable to that in other populations of patients. CONCLUSIONS: Despite a high propensity for developing pulmonary infections, hospitalized patients with hematologic malignancies rarely developed complex parapneumonic effusions. The etiology of many of the effusions that occurred in this setting was unclear.

Drug-induced pulmonary infection.

Immunosuppressive drugs lead to an enhanced risk for infection. The impact of these drugs on the immune system can be broad (eg, corticosteroids) or targeted (eg, rituximab). Infections can have serious consequences, particularly if there is a delay in diagnosis. It is hoped that a knowledge of the type of immune defects that are induced by these drugs and the specific infections that have been reported will guide clinicians in the appropriate use of prophylactic regimens and diagnostic considerations in the event of pneumonia.

Role of fine-needle aspirates of focal lung lesions in patients with hematologic malignancies.

OBJECTIVES: To evaluate the yield and safety of transthoracic fine-needle aspiration (FNA) in the diagnosis of pulmonary disease in patients with hematologic malignancy. DESIGN: Retrospective chart review. SETTING: Tertiary-care medical center. PATIENTS: Sixty-seven patients with a hematologic malignancy or after bone marrow transplantation (BMT) for a hematologic malignancy who underwent a total of 71 FNAs for diagnosis of an unexplained parenchymal lung lesion from January 1, 1991, to June 30, 1999. RESULTS: The underlying malignancy was lymphoma in 42 patients (63%), leukemia in 8 patients (12%), after allogeneic BMT in 12 patients (18%), after autologous BMT in 3 patients (4%), and other diseases in 2 patients. Radiographs showed focal abnormalities in all cases, and were nodules in 37%, masses in 37%, focal infiltrates in 21%, and cavitary lesions in 5%. The yield of FNA for a finding specific infection or cancer was 56% (40 of 71 FNAs). The FNA with inflammatory changes was clinically sufficient in another 11 patients for a total yield of 72% (51 of 71 FNAs). The yield for lung cancer was 90% (9 of 10 FNAs), for pulmonary lymphoma was 68% (21 of 31 FNAs), and for infection was 67% (10 of 15 FNAs). Complications occurred in 18 of 71 FNAs (25%), with pneumothorax in 14 patients (20%) and chest tube placement required in 4 patients (6%). Bleeding occurred in six patients (8%), including one death in a patient with abnormal hematologic parameters. CONCLUSION: Transthoracic FNA in patients with hematologic malignancy and focal lung lesions has an excellent yield for detecting cancer and a yield comparable to bronchoscopy for the diagnosis of infections. It should be considered a useful diagnostic tool in this setting.