Evaluating the health-related quality of life effects of cochlear implants: a prospective study of an adult cochlear implant program

This paper prospectively documents the health-related quality of life (HRQoL) and social participation benefits of adult patients receiving cochlear implants in Australia and New Zealand. Thirty-four consecutively implanted patients completed the Assessment of Quality of Life (AQoL) and Hearing Participation Scale (HPS) instruments before implantation, and at 3- and 6-month follow-ups. Implantation resulted in significant improvements in AQoL and HPS scores, The effect size was 1.09 for both measures. Those in the top socio-economic tertile obtained the greatest gains. The HRQoL and social participation benefits were slightly larger than those reported elsewhere. This may be because participants used more recent technology (Nucleus 24 rather than Nucleus 22) and received auditory and self-efficacy training as part of their rehabilitation. The results suggest that cochlear implants have a large beneficial effect. They show that social and HRQoL outcomes can be parsimoniously measured using the HPS and AQoL instruments.     

Sex differences in outcomes after cardiac catheterization: effect modification by treatment strategy and time

Context  Studies comparing outcomes of cardiac care in women vs men yield various results, with some suggesting worse outcomes for women and others suggesting equivalent outcomes. Objective  To determine whether extent of coronary disease, treatment strategy, and follow-up time influence the risk of death in women vs men among patients who have had cardiac catheterization. Design, Setting, and Patients  We studied a large inception cohort by using detailed clinical data from a registry of 37 401 patients undergoing cardiac catheterization in Alberta, Canada, from 1995-2000, with follow-up through December 31, 2001. Main Outcome Measures  The risk of death for women vs men was assessed for all patients combined and then in analyses stratified by degree of coronary anatomic risk and by treatment strategy (no revascularization, percutaneous coronary intervention [PCI], coronary artery bypass graft [CABG] surgery). The latter analysis included a graphic assessment of the changing relative risk over time for women vs men. Results  Women had higher 1-year mortality than men did (5.6% vs 4.6%; P<.001). However, stratified analyses demonstrated that sex differences in risk occurred only early after catheterization and were most apparent among patients undergoing revascularization. The early risk-adjusted relative risks for women vs men were elevated at 3.49 (95% confidence interval [CI], 1.95-6.24) for CABG surgery and 2.38 (95% CI, 1.48-3.83) for PCI on day 1 after catheterization, with a subsequent decrease in relative risk over time to equivalence in risk between sexes before 1 year. Conclusions  Sex-based differences in death rates after cardiac catheterization are time- and treatment-specific. This finding may at least partially explain the discrepancies in results from earlier studies on sex differences in outcomes of cardiac care.      

Self-injurious behaviour: a comparison of caffeine and pemoline models in rats

Self-injurious behaviour (SIB) is a debilitating behaviour disorder that can have life-threatening consequences. It is often exhibited in intellectually handicapped and autistic populations, and it has been modeled with pharmacological manipulations in animals. We have characterized the induction of SIB using high doses of caffeine and pemoline in rats. Caffeine only produced very mild SIB in a small proportion of the rats, when administered repeatedly at very high doses (140-185 mg/kg/day). All the caffeine-treated rats showed profound signs of caffeine-toxicity at these doses, and lower doses did not induce any self-injury. On the other hand, pemoline was effective across a range of doses (100-300 mg/kg/day), including doses that did not produce overt signs of toxicity (100-200 mg/kg/day). The topography of the tissue injury sites (tail vs. paws and ventrum) differed between caffeine and pemoline treatments, and across doses of pemoline. The speed of onset, the incidence, and the severity of SIB occurred in a dose-orderly manner across the pemoline doses, and there was substantial individual variability in the induction of SIB when a moderately high dose (200 mg/kg/day) was used. These individual differences in vulnerability to self-injure are reminiscent of the fact that some humans with specific neurobiological disorders express SIB and some individuals with those same disorders do not. Accordingly, the pemoline model of SIB may be useful to investigate the neurobiological basis of factors that contribute to etiology of SIB.     

A Phase II study of docetaxel and carboplatin as neoadjuvant therapy for nasopharyngeal carcinoma with early T status and advanced N status

BACKGROUND: Promising results from a Phase II trial of induction chemotherapy and sequential radiotherapy for advanced nasopharyngeal carcinoma (NPC) at The University of Texas M. D. Anderson Cancer Center (Houston, TX) and two retrospective reviews of the authors' historical experience with NPC demonstrated that distant failure was directly correlated with advanced lymph node status. Furthermore, local control was excellent for patients with T1-3 disease that was managed with radiation alone or with a sequential approach involving chemotherapy. Neoadjuvant chemotherapy (primarily with cisplatin + 5-fluorouracil) was associated with a significantly decreased risk of distant metastasis and with improved survival. Based on these findings, the authors evaluated a novel induction regimen involving docetaxel and carboplatin for patients with previously untreated T1-2N2-3M0 NPC. METHODS: Docetaxel (80 mg/m2 on Day 1) and carboplatin (to an area under the time-concentration curve of 6 on Day 1) were administered every 21 days for 3 cycles, after which radiotherapy was administered. NPC was restaged with magnetic resonance imaging and nasopharyngoscopy 3 weeks after the completion of chemotherapy and 6 weeks after the completion of radiotherapy. RESULTS: Over 5 years, 18 patients were enrolled in the study. Grade 4 neutropenia and Grade 2 fatigue were observed in 51% and 28% of chemotherapy courses, respectively. After chemotherapy, 2 patients had complete responses, 14 had partial responses, 1 had a minor response, and 1 had progressive disease. The latter two patients and one patient who had a partial response underwent off-study chemoradiotherapy. After radiotherapy or chemoradiotherapy, 12 patients had complete responses and 6 had partial responses. Seven patients had recurrent disease; two had local recurrences, and five had distant metastases. CONCLUSIONS: Although unlikely to be superior to cisplatin + 5-fluorouracil, the trial regimen could be administered quickly in the outpatient setting, was logistically more convenient for the patient, and was devoid of serious nonhematologic toxic effects. We believe that the risk-based approach examined in the current study merits further investigation.     

A phase I/II trial of induction chemotherapy with carboplatin and gemcitabine followed by concurrent vinorelbine and paclitaxel with chest radiation in patients with stage III non-small cell lung cancer

PURPOSE: We designed a phase I/II trial in order to evaluate the efficacy and tolerability of induction carboplatin and gemcitabine and the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of subsequent chemoradiotherapy with weekly vinorelbine and paclitaxel in patients with stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients had pathologically confirmed N2-N3 stage NSCLC, adequate end-organ function, and ECOG performance status 0-2. Carboplatin was administered at an AUC of 5 on day 1 and gemcitabine 1000 mg/m2 on days 1 and 8, every 21 days, for two cycles, followed by weekly vinorelbine 10-15 mg/m2 and paclitaxel 50 mg/m2 and conventional chest radiotherapy up to 66 Gy. Patients with resectable disease underwent thoracotomy after 40-45 Gy. RESULTS: Thirty-nine eligible patients were enrolled; 17 had stage IIIB NSCLC. Grade 3 esophagitis developed in 4/5 patients on the second dose level of chemoradiotherapy (i.e. vinorelbine 15 mg/m2) and was considered dose-limiting. Of 34 patients treated at the maximum tolerated dose (i.e. vinorelbine 10 mg/m2), 2 patients (6%) had pneumonitis >grade 2 and 3 (9%), esophagitis >grade 2. Induction chemotherapy was well tolerated with only one patient developing >grade 2 non-hematologic toxicity (nausea). Forty-one percent of patients had an objective response after induction chemotherapy and 51% after chemoradiotherapy. Nineteen patients, 16 of whom had stage IIIA, underwent surgical resection. The pathologic complete response rate was 16% (42% in the mediastinal lymph nodes). With a median follow-up of 31 months, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 23 and 34%, respectively, and the median OS was 25 months. CONCLUSIONS: We identified a well-tolerated and active chemoradiotherapy regimen. Survival results are promising and the addition of a biologic agent to this regimen is of interest.     

The role of cervical lymphadenectomy after aggressive concomitant chemoradiotherapy: the feasibility of selective neck dissection

OBJECTIVES: To evaluate the necessity, technical feasibility, and complication rate of neck dissection performed on patients with head and neck cancer after 5 cycles of concomitant chemoradiotherapy (CRT) and to justify a selective neck dissection (SND) approach and define the optimal timing of post-CRT neck dissection. DESIGN AND SETTING: Retrospective analysis in an academic university medical center. PATIENTS: Sixty-nine eligible patients with advanced (stage III and IV) head and neck cancer who have undergone 1 of 4 CRT protocols. Patients ranged in age from 36 to 75 years, and surgical procedures were performed over a 4-year period. Follow-up ranged from 6 to 64 months. INTERVENTION: Neck dissection (most commonly unilateral SND) performed within 5 to 17 weeks after CRT completion. MAIN OUTCOME MEASURES: Complication rate and incidence of positive pathology (viable cancer) in pathologic neck dissection specimens. RESULTS: Seven (10%) of 69 patients developed wound healing complications, 4 (6%) of whom required surgical intervention for ultimate closure. There were no wound infections. Other complications occurred in 11 (16%) of 69 patients and included need for tracheotomy, nerve transection and paresis, and permanent hypocalcemia. Twenty-four (35%) of 69 patients revealed microscopic residual disease. Ten (50%) of 20 patients with N3 neck disease had positive pathology, whereas 14 (36%) of 39 patients with N2 disease had viable carcinoma in the dissection specimen (P =.09 by chi(2) analysis). There was no significant relation between radiologic complete response or partial response and residual microscopic cancer. In 1 patient, disease recurred in the neck after dissection. Mean follow-up time was 30.3 months. CONCLUSIONS: (1) Neck dissection for patients with N2 or greater neck disease after CRT is necessary to eradicate residual disease. (2) The complication rate of SND after CRT with hyperfractionated radiotherapy is low. (3) SNDs are technically feasible when performed within the "window" between the acute and chronic CRT injury (4-12 weeks). (4) SNDs, rather than more radical procedures, appear to be therapeutically appropriate in this group of patients because of the low incidence of disease recurrence in the neck.