A randomized comparison of fluconazole with amphotericin B as empiric anti-fungal agents in cancer patients with prolonged fever and neutropenia

The severity of heterochromia on sun-damaged skin is a good indicator for the risk of development of a skin cancer. Clinical photography under ultraviolet light allows to objectivate such a risk factor.     

Randomized, double-blind clinical trial of amphotericin B colloidal dispersion vs. amphotericin B in the empirical treatment of fever and neutropenia

The possibility that there is an inhibitory component to auditory covert orienting was addressed. Each trial consisted of a cue followed by a target, and listeners were required to detect, localize, or identify the frequency of the target. At 150-msec stimulus onset asynchrony (SOA), performance was best when stimuli sounded from the same location or were of the same frequency. However, at 750-msec SOA, performance was best when stimuli differed in location or were of different frequencies. These results document the existence of both location-based and frequency-based auditory inhibition of return.     

Current treatment of candidemia in non-neutropenic patients. Amphotericin B or fluconazole? A retrospective study of 62 consecutive patients

BACKGROUND: To analyze the epidemiologic characteristics of non-neutropenic patients with candidemia in a general hospital and the advantages and disadvantages of treatment with amphotericin B or fluconazole. PATIENTS AND METHODS: A total of 62 adult non-neutropenic patients with candidemia and treated with amphotericin B (n = 35) or fluconazole (n = 27) were studied. All episodes were considered to be associated with infection in a vein catheter. The demographic characteristics, risk factors for the development of candidemia, Candida species recovered from blood culture, underlying diseases, and clinical manifestations in both groups were compared. The evolution regarding secondary effects developed with both drugs, therapy failures, long term complications, and overall mortality rate associated with candidemia were analyzed. RESULTS: Both groups were comparable with the exception of the percentage of patients infected with species different from Candida albicans, which was higher in the group of patients who received amphotericin B (57%) than in the fluconazole group (26%) (p = 0.02), and in that patients with severe renal failure or AIDS had received preferentially fluconazole. There were no statistically significant differences regarding the evolution of patients treated with amphotericin B or fluconazole with the following factors: therapy failure (27% versus 19%; p = 0.7), overall mortality rate (40% versus 44%; p = 0.6), and mortality directly related to candidemia (33% versus 30%). Mortality was significantly higher among patients who had not their vein catheters removed early (78%) compared with those who had their vein catheters removed early (34%) (p = 0.01). Sixty-six percent of patients treated with amphotericin developed some severe secondary effect, whereas no patient in the fluconazole group developed such effects. CONCLUSIONS: Both amphotericin B and fluconazole seem to be effective drugs for the treatment of vein catheter related candidemia in the non-neutropenic patient, although fluconazole is far less toxic. The early removal of the vein catheter plays a prognostic role with at least the same relevance than the type of antifungal therapy chosen.     

A randomized trial in patients inadequately controlled with timolol alone comparing the dorzolamide-timolol combination to monotherapy with timolol or dorzolamide. Dorzolamide-Timolol Combination Study Group

OBJECTIVE: To compare the dorzolamide-timolol fixed combination twice daily to its components, timolol maleate and dorzolamide hydrochloride, given in their usual monotherapy regimens in patients whose intraocular pressure (IOP) was not controlled on timolol twice daily alone. DESIGN: Parallel, randomized, double-masked, and active-controlled study. PARTICIPANTS: Enrolled were 253 patients from 22 sites throughout the United States. INTERVENTION: After a 3-week run-in of timolol (TIMOPTIC; Merck & Co., Inc., Whitehouse Station, NJ) twice daily, eligible patients received either the combination (COSOPT; Merck & Co., Inc., Whitehouse Station, NJ) twice daily (plus placebo to ensure masking), timolol twice daily (plus placebo to ensure masking), or dorzolamide (TRUSOPT; Merck & Co. Inc., Whitehouse Station, NJ) three times daily for 3 months. MAIN OUTCOME MEASURES: Intraocular pressure taken at hours 0 (trough) and 2 (peak) after week 2 and months 1, 2, and 3 was compared to baseline within each treatment group and between the combination and each component group. The safety profile of the combination was compared to each component. RESULTS: The combination was numerically superior at all study timepoints and was statistically superior at all timepoints except for month 2, hour 0 for timolol, and month 2, hour 2 for dorzolamide. The safety profile of the combination reflected those of its two components. The number of patients reporting ocular or local adverse experiences was greater for the combination (45%) and dorzolamide (45%) than for timolol (27%), with burning and/or stinging eye being the most frequently reported. CONCLUSION: The dorzolamide-timolol combination provides additional IOP lowering compared to either of its individual components and generally is well-tolerated.     

A randomized, double-blind clinical trial comparing cefepime plus metronidazole with imipenem-cilastatin in the treatment of complicated intra-abdominal infections. Cefepime Intra-abdominal Infection Study Group

OBJECTIVE: To evaluate the safety and efficacy of cefepime hydrochloride plus metronidazole vs the combination of imipenem and cilastatin sodium in the treatment of complicated intra-abdominal infections in adult patients. DESIGN: Prospective, randomized, double-blind multicenter study. SETTING: University-affiliated hospitals in the United States and Canada. PATIENTS: Three hundred twenty-three patients with complicated intra-abdominal infections in whom an operative procedure or percutaneous drainage was required for diagnosis and management. INTERVENTION: Cefepime, 2 g, was administered intravenously every 12 hours (n= 164) in addition to metronidazole, 500 mg (or 7.5 mg/kg) intravenously every 6 hours. Imipenen-cilastatin sodium, 500 mg, was administered intravenously every 6 hours (n= 159). Surgical infection management was determined by the patients' surgeons. MAIN OUTCOME ASSESSMENTS: Clinical cure, defined as elimination of all signs and symptoms relevant to the original infection; and treatment failure, defined as persistence, increase or worsening of signs and symptoms resulting in an antibiotic change, requirement of an additional surgical procedure to cure the infection, or a wound infection with fever. RESULTS: Of the initial isolates, 84% were susceptible to cefepime and 92% were susceptible to imipenem-cilastatin. Among the 217 protocol-valid patients, those treated with cefepime+metronidizole were deemed clinical cures (88%) more frequently than were imipenem-cilastatin-treated patients (76%) (P=.02). Using multivariate analysis to adjust for identified clinical risk factors for an adverse outcome (severity of presenting illness, isolation of enterococcus, type of infection, and duration of prestudy hospitalization), there was a trend (P=.06) toward a higher cure rate favoring cefepime+metronidazole. Pathogens were eradicated in significantly (P=.01) more patients treated with combined cefepime and metronidazole (89%) than with imipenem-cilastatin (76%). CONCLUSION: The combination of cefepime plus metronidazole is safe and effective therapy for patients with severe intra-abdominal infections.     

An EORTC international multicenter randomized trial (EORTC number 19923) comparing two dosages of liposomal amphotericin B for treatment of invasive aspergillosis

Experiments were performed to determine the actions of recombinant bovine interleukin-1beta (IL-1beta) on the growth of preimplantation embryos. In the first series of studies, IL-1beta was added at 8-10 h after insemination, and the percentage of oocytes developing to the blastocyst stage was evaluated. IL-1beta increased development to the blastocyst stage when embryos were cultured at high density ( approximately 25-30 embryos/drop) but decreased or had no effect on development when cultured at low density ( approximately 10 embryos/drop). Thus, the positive effect of IL-1beta depends upon some other embryo-derived product. The effect of IL-1beta on embryonic development was maintained in completely denuded embryos, indicating that cumulus cells do not mediate the actions of IL-1beta. Maximum development of embryos cultured at approximately 25-30/drop occurred at 0.1-1 ng/ml; 10 ng/ml was less effective. Addition of IL-1beta to groups of approximately 25-30 embryos/drop at 8-10 h after insemination also increased embryo cell number at Day 5 postinsemination by increasing the proportion of embryos that reached the 9- to 16-cell stage. However, IL-1beta had no effect on the proportion of blastocysts when added at Day 5 postinsemination. Thus, IL-1beta probably acts to increase blastocyst numbers by exerting actions on embryo growth before Day 5. In contrast to its effect on embryos, addition of IL-1beta during oocyte maturation did not affect cumulus expansion, cleavage rate of oocytes, or subsequent development to the blastocyst stage. In conclusion, IL-1beta can modulate growth of bovine embryos at early stages of development in a manner dependent upon embryo density.     

A randomized controlled trial of filgrastim as an adjunct to antibiotics for treatment of hospitalized patients with community-acquired pneumonia. CAP Study Group

OBJECTIVE: The aims of the study were to follow prospectively the intrasubject progression of idiopathic PD in a cohort of patients using levodopa kinetic-dynamic modeling and to assess the relation between the rate of progression of the disease and patients' different clinical characteristics. METHODS: Thirty-four patients (Hoehn and Yahr stages 1 to 3) enrolled in the longitudinal follow-up. Each patient was examined at 1-year intervals over a median 4 years by a standardized oral levodopa test. The primary measure outcome was the computed half-life of levodopa in the "effect compartment" (t1/2eq), a proposed indicator of nigrostriatal dopaminergic functionality and integrity. RESULTS: Values of levodopa t1/2eq correlated negatively with severity of symptoms (r = -0.652, p < 0.0001) and decreased over the years together with a worsening of patients' clinical stage (p < 0.001). The rate of reduction in drug t1/2eq was more rapid in patients at the earlier stages of the disease compared with the more advanced ones, falling from a median annual reduction of 37 minutes in patients at initial Hoehn and Yahr stage 1 to 6.5 minutes in stage 3 patients (p < 0.001). Patients without tremor at onset, otherwise comparable to patients with tremor for baseline values of levodopa t1/2eq, disease severity, duration, and daily dose of levodopa, tended to show a higher rate of reduction in levodopa t1/2eq than patients with tremor. Overall, patients' annual reduction in levodopa t1/2eq over baseline values averaged 17+/-9%. CONCLUSIONS: These results are in keeping with PET findings on the objective assessment of idiopathic parkinsonism evolution, and they support the suggestion that levodopa pharmacodynamic modeling may offer a practical clinical tool to assess indirectly the functional integrity of the nigrostriatal dopaminergic system over time in parkinsonian patients.     

A randomized comparison of liposomal versus conventional amphotericin B for the treatment of pyrexia of unknown origin in neutropenic patients

One hundred and thirty-four adults and 204 children were randomized in two prospective, parallel comparative multicentre trials to receive either conventional amphotericin B 1 mg/kg/d (c-AMB), liposomal amphotericin B 1 mg/kg/d(L-AMB1) or liposomal amphotericin B 3 mg/ kg/d (L-AMB3). Patients were entered if they had a pyrexia of unknown origin (PUO) defined as temperature of 38 degrees C or more, not responding to 96 h of systemic broad-spectrum antibiotic treatment, and neutropenia (< 0.5 x 10(9)/l). The safety and toxicity of liposomal amphotericin B was compared with that of conventional amphotericin B. Efficacy of treatment was assessed, with success defined as resolution of fever for 3 consecutive days (< 38 degrees C) without the development of any new fungal infection. Clinical and laboratory parameters were collected for safety analysis. In both the paediatric and adult populations, L-AMB treated patients had a 2-6-fold decrease in the incidence (P < or = 0.01) of test-drug-related side-effects, compared to c-AMB. Severe trial-drug-related side-effects were seen in 1% of L-AMB treated patients, in contrast to 12% of patients on c-AMB (P < 0.01). Nephrotoxicity, in the patient subset not receiving concomitant nephrotoxic agents, defined as a doubling from the patients baseline serum creatinine level, was not observed in the L-AMB1 arm whereas the incidence was 3% in patients on L-AMB3 and 23% in those on c-AMB (P < 0.01). Moreover, time to develop nephrotoxicity was longer in both L-AMB arms than c-AMB (P < 0.01). Severe hypokalaemia was observed less frequently in both L-AMB arms (P < 0.01). Analysis was by intention-to-treat and included all patients randomized. Success was defined by a minimum of 3 consecutive days with fever (< 38 degrees C) continuing to study end indicated by recovery of neutrophils to 0.5 x 10(9)/l. Addition of systemic antifungal therapy or development of systemic fungal infection were failures as was persistent fever to study end. Efficacy assessments indicated success in 49% of the total group treated with c-AMB, 58% of patients responded to L-AMB1 and 64% to L-AMB3. A statistically significant difference was found between c-AMB and L-AMB3 (P = 0.03) but a Kaplan-Meier analysis of time to differvescence of fever showed there was no significant difference between the arms. It was concluded that liposomal amphotericin at either 1 or 3 mg/kg/d was significantly safer than conventional amphotericin B in children and adults. The main aim of this open-label study was to compare safety between the three trial arms. However, we provide evidence for an equivalent or possibly superior efficacy of liposomal amphotericin with regard to resolution of fever of unknown origin. Subsequent trials should compare amphotericin preparations in defined fungal infections.     

A prospective randomized trial comparing somatostatin and sclerotherapy in the treatment of acute variceal bleeding

Somatostatin and endoscopic sclerotherapy are widely used in the treatment of acute variceal bleeding. Although objective evidence does exist about the advantages of either treatment, data comparing both procedures are scarce. In order to compare the effectiveness and safety of somatostatin and sclerotherapy in the treatment of acute variceal bleeding, 70 consecutive cirrhotic patients suffering from esophageal variceal hemorrhage and meeting the inclusion criteria were randomly assigned to treatment with somatostatin (35 patients) or sclerotherapy (35 patients). No differences in age, sex, alcohol intake, etiology of cirrhosis and severity of liver failure were found between groups. Failure of treatment (defined as persistence of bleeding despite therapy or subsequent rebleeding within the 48-hr trial period) occurred in seven patients (20%) in the somatostatin group and in six (17.1%) in the sclerotherapy group (NS). Early rebleeding occurred in seven of 28 patients (25%) in the somatostatin group and in five of 29 (17.2%) in the sclerotherapy group (NS). Mortality within the first 6 wk was no different between both groups: 10 (28.5%) and eight (22.8%) in the somatostatin and sclerotherapy groups, respectively. Sclerotherapy, but not somatostatin, was associated with major complications in five cases (14.2%) (p = 0.026), two of which resulted in patient's death. These results suggest that somatostatin is safer, and as effective as sclerotherapy, in controlling acute variceal bleeding until an elective treatment can be established.     

A randomized trial comparing day and residential drug abuse treatment: 18-month outcomes.

Extending an earlier report of 6-month outcomes, this study reports 12- and 18-month follow-up data for clients (N?=?188) entering a therapeutic community drug treatment program who were randomly assigned to day or residential treatment conditions. Outcomes included Addiction Severity Index composite scores and measures of depression, psychiatric symptoms, and social support. Both groups showed significant change over time. The pattern of change indicated decreased problem severity in the 1st 6 months and then maintenance of lowered problem severity. Comparisons between groups indicated greater improvement for residential treatment clients on social problems and psychiatric symptoms but no differences on the remaining outcomes. Although residential treatment may offer some specific advantages, the conclusion here is that improvement among day treatment clients was not significantly different from that of residential treatment clients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hypnotic taper with or without self-help treatment of insomnia: A randomized clinical trial.

This study aimed to assess the efficacy of a minimal intervention focusing on hypnotic discontinuation and cognitive-behavioral treatment (CBT) for insomnia. Fifty-three adult chronic users of hypnotics were randomly assigned to an 8-week hypnotic taper program, used alone or combined with a self-help CBT. Weekly hypnotic use decreased in both conditions, from a nearly nightly use at baseline to less than once a week at posttreatment. Nightly dosage (in lorazepam equivalent) decreased from 1.67 mg to 0.12 mg. Participants who received CBT improved their sleep efficiency by 8%, whereas those who did not remained stable. Total wake time decreased by 52 min among CBT participants and increased by 13 min among those receiving the taper schedule alone. Total sleep time remained stable throughout withdrawal in both CBT and taper conditions. The present findings suggest that a systematic withdrawal schedule might be sufficient in helping chronic users stop their hypnotic medication. The addition of a self-help treatment focusing on insomnia, a readily available and cost-effective alternative to individual psychotherapy, produced greater sleep improvement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A randomized controlled trial comparing two vocational models for persons with severe mental illness.

The authors compared 2 approaches to vocational rehabilitation for individuals with severe mental illness: the individual placement and support (IPS) model of supported employment and the diversified placement approach (DPA), which emphasizes work readiness and offers a range of vocational options, including agency-run businesses and agency-contracted placements with community employers. In all, 187 unemployed participants with severe mental illness were randomly assigned to IPS or DPA. Over 2 years, IPS had significantly better competitive employment outcomes than DPA. Competitive employment rates over the 2-year follow-up were 75.0% for IPS and 33.7% for DPA. However, IPS and DPA did not differ on paid employment outcomes. The authors conclude that IPS is more effective than DPA in achieving competitive employment, but not paid employment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A randomized prospective trial comparing 45 and 90-ml oral sodium phosphate with X-Prep in the preparation of patients for colonoscopy

Incontinentia pigmenti is an uncommon genodermatosis that occurs in female infants. The characteristic dental defects are partial anodontia and the presence of some peg-shaped teeth. This report describes a patient with incontinentia pigmenti who exhibited multiple missing teeth in both arches. The patient had malpositioned teeth and decreased occlusal vertical dimension associated with the missing teeth. Orthodontic treatment was required for prosthetic purposes. The dental anomalies of incontinentia pigmenti and the treatment procedure are presented.     

Amphotericin B colloidal dispersion combined with flucytosine with or without fluconazole for treatment of murine cryptococcal meningitis

Junctional epidermolysis bullosa is a heritable, heterogeneous blistering skin disease with mechanically induced dermal-epidermal separation, mild skin atrophy, nail dystrophy, and alopecia. Four unrelated junctional epidermolysis bullosa families with different phenotypes were investigated here and four novel mutations associated with the disease were identified. Patients 1, 2, and 3 had generalized atrophic benign epidermolysis bullosa, with nonscarring blistering and varying degree of alopecia. Patient 4 had the localisata variant of junctional epidermolysis bullosa, with predominantly acral blistering and normal hair. All patients had mutations in the COL17A1 gene encoding collagen XVII, a hemidesmosomal transmembrane protein. Patients 1 and 2 carried homozygous deletions 520delAG and 2965delG, respectively. Patient 3 was compound heterozygous for a missense and a deletion mutation (G539E and 2666delTT), and patient 4 was heterozygous for a known mutation R1226X. The deletions led to premature termination codons and to drastically reduced collagen XVII mRNA and protein levels, consistent with the absence of the collagen in generalized atrophic benign epidermolysis bullosa skin. The missense mutation G539E allowed synthesis of immunoreactive collagen XVII in keratinocytes, but prevented its secretion, thus causing lack of the protein in the skin. The data suggest that different COL17A1 mutations and their combinations can result in a spectrum of biologic and clinical phenotypes of not only generalized atrophic benign epidermolysis bullosa, but also localized junctional epidermolysis bullosa.     

Computer-assisted cognitive rehabilitation for the treatment of patients with substance use disorders: A randomized clinical trial.

The purpose of this study was to examine the comparative efficacy of cognitive rehabilitation as an intervention for substance misuse. Patients with substance use disorders entering long-term residential care (N = 160) were randomly assigned to one of two conditions: (a) standard treatment plus computer-assisted cognitive rehabilitation (CACR), which was designed to improve cognitive performance in areas such as problem solving, attention, memory, and information processing speed; and (b) an equally intensive attention control condition consisting of standard treatment plus a computer-assisted typing tutorial (CATT). Participants were assessed at baseline, during treatment, at treatment completion, and 3-, 6-, 9-, and 12-month follow-up. Intent-to-treat analyses showed that, compared with those randomized to CATT, patients who received CACR were significantly more engaged in treatment (e.g., higher ratings of positive participation by treatment staff, higher ratings of therapeutic alliance), more committed to treatment (e.g., longer stays in residence) and reported better long-term outcomes (e.g., higher percentage of days abstinent after treatment). Mediational analyses revealed the positive comparative effect of CACR on abstinence during the year after treatment was mediated by treatment engagement and length of stay in residence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. The Severe Pneumonia Study Group

Intravenously administered ciprofloxacin was compared with imipenem for the treatment of severe pneumonia. In this prospective, randomized, double-blind, multicenter trial, which included an intent-to-treat analysis, a total of 405 patients with severe pneumonia were enrolled. The mean APACHE II score was 17.6, 79% of the patients required mechanical ventilation, and 78% had nosocomial pneumonia. A subgroup of 205 patients (98 ciprofloxacin-treated patients and 107 imipenem-treated patients) were evaluable for the major efficacy endpoints. Patients were randomized to receive intravenous treatment with either ciprofloxacin (400 mg every 8 h) or imipenem (1,000 mg every 8 h), and doses were adjusted for renal function. The primary and secondary efficacy endpoints were bacteriological and clinical responses at 3 to 7 days after completion of therapy. Ciprofloxacin-treated patients had a higher bacteriological eradication rate than did imipenem-treated patients (69 versus 59%; 95% confidence interval of -0.6%, 26.2%; P = 0.069) and also a significantly higher clinical response rate (69 versus 56%; 95% confidence interval of 3.5%, 28.5%; P = 0.021). The greatest difference between ciprofloxacin and imipenem was in eradication of members of the family Enterobacteriaceae (93 versus 65%; P = 0.009). Stepwise logistic regression analysis demonstrated the following factors to be associated with bacteriological eradication: absence of Pseudomonas aeruginosa (P < 0.01), higher weight (P < 0.01), a low APACHE II score (P = 0.03), and treatment with ciprofloxacin (P = 0.04). When P. aeruginosa was recovered from initial respiratory tract cultures, failure to achieve bacteriological eradication and development of resistance during therapy were common in both treatment groups (67 and 33% for ciprofloxacin and 59 and 53% for imipenem, respectively). Seizures were observed more frequently with imipenem than with ciprofloxacin (6 versus 1%; P = 0.028). These results demonstrate that in patients with severe pneumonia, monotherapy with ciprofloxacin is at least equivalent to monotherapy with imipenem in terms of bacteriological eradication and clinical response. For both treatment groups, the presence of P. aeruginosa had a negative impact on treatment success. Seizures were more common with imipenem than with ciprofloxacin. Monotherapy for severe pneumonia is a safe and effective initial strategy but may need to be modified if P. aeruginosa is suspected or recovered from patients.     

Group support for patients with metastatic cancer. A randomized outcome study

The effects of weekly supportive group meetings for women with metastatic carcinoma of the breast were systematically evaluated in a one-year, randomized, prospective outcome study. The groups focused on the problems of terminal illness, including improving relationships with family, friends, and physicians and living as fully as possible in the face of death. We hypothesized that this invention would lead to improved mood, coping strategies, and self-esteem among those in the treatment group. Eighty-six patients were tested at four-month intervals. The treatment group had significantly lower mood-disturbance scores on the Profile of Mood States scale, had fewer maladaptive coping responses, and were less phobic than the control group. This study provides objective evidence that a supportive group intervention for patients with metastatic cancer results in psychological benefit. Mechanisms underlying the effectiveness of this group intervention are explored.     

A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis. Myasthenia Gravis Study Group

Noninvasive alternatives to esophageal pressure (Pes) are needed to evaluate respiratory effort during sleep. Pulse transit time (PTT) is the time taken for pulse pressure to travel from the aortic valve to the periphery. PTT has been shown to be inversely correlated with blood pressure, and can reveal acute changes generated by high pleural pressure swings during pulsus paradoxus. A close relationship has been demonstrated between the increase in Pes and a progressive rise in the amplitude of PTT oscillations. The aim of the present study was to assess the accuracy of PTT for the classification of sleep respiratory events as central or obstructive. Respiratory events occurring during sleep were randomly chosen from 13 unselected male patients (mean apnea-hypopnea index [AHI] = 25.1 per hour of sleep; age = 47.3 yr, body mass index [BMI] = 27.1 kg/m2). Two observers experienced in polysomnography classified 177 events on the basis of the "gold standard method": the measurement of Pes. For 167 events about which the observers agreed, the PTT signal was analyzed visually and independently by the two observers blinded to Pes, in order to reclassify the same sleep respiratory events. The two observers were in agreement for 94.6% of the events scored visually on PTT recordings. We evaluated sensitivity (Se) (Observer 1: 94%, Observer 2: 91%), specificity (Sp) (97% and 95%, respectively), negative predictive value (NPV) (95% and 92%, respectively), and positive predictive value (PPV) (96% and 94%, respectively), of PTT with Pes as the reference. Misclassifications of respiratory episodes were usually due to artifacts or baseline variations of the PTT signal (57%), and occurred during rapid eye movement (REM) sleep (42.8%). PTT has shown a high sensitivity and specificity in differentiating obstructive and central respiratory events, and may become the reference noninvasive tool for this purpose.     

Preliminary report of the Asian-Oceanian Clinical Oncology Association randomized trial comparing cisplatin and epirubicin followed by radiotherapy versus radiotherapy alone in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. Asian-Oceanian Clinical Oncology Association Nasopharynx Cancer Study Group

BACKGROUND: The aim of this trial was to compare the outcome achieved with neoadjuvant chemotherapy followed by radiotherapy to that achieved with radiotherapy alone for patients with locoregionally advanced undifferentiated or poorly differentiated nasopharyngeal carcinoma (NPC) meeting one of the following criteria: Ho's T3 disease, Ho's N2-N3 disease, or lymph node size > or =3 cm. METHODS: Between September 1989 and August 1993, 334 patients were enrolled in the study, with equal numbers of patients randomized to the neoadjuvant chemotherapy arm (CT arm) and the radiotherapy arm (RT arm). Neoadjuvant chemotherapy consisting of 2-3 cycles of cisplatin (60 mg/m2 on Day 1) and epirubicin (110 mg/m2 on Day 1) followed by radiotherapy was given to the CT arm. For radiotherapy, a dose of 66-74 gray (Gy) (median, 71 Gy) was delivered to the primary tumor and 60-76 Gy (median, 66 Gy) to the neck. Two hundred eighty-six eligible patients completed the treatment and were evaluable for treatment response (134 in the CT arm, 152 in the RT arm). All patients were included in the survival analysis based on the intention to treat. The median follow-up was 30 months for the whole cohort and 41 months for the surviving patients. RESULTS: Analysis of the 334 patients based on the intention to treat showed no significant difference in relapse free survival (RFS) or overall survival (OS) between the 2 treatment arms (3-year RFS rate: 48% in the CT arm vs. 42% in the RT arm, P = 0.45; 3-year OS rate: 78% vs. 71%, P = 0.57). In an efficacy analysis based on only the 286 evaluable patients, a trend of improved RFS favoring the CT arm was observed (3-year RFS rate: 58% vs. 46%, P = 0.053), with again no significant difference in OS (3-year OS rate: 80% vs. 72%, P = 0.21). In the subgroup of 49 patients with bulky neck lymph nodes >6 cm, improved RFS (3-year RFS rate: 63% vs. 28%, P = 0.026) and OS (3-year OS rate: 73% vs. 37%, P = 0.057) were observed, favoring the CT arm. CONCLUSIONS: This multicenter randomized study did not demonstrate any benefit with the addition of cisplatin-epirubicin neoadjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma; therefore routine administration of neoadjuvant chemotherapy to this target group cannot be recommended. Although the overall incidence of recurrence was reduced with the addition of chemotherapy in the efficacy analysis, the overall survival was not affected. A more effective chemotherapy regimen, the selection of an appropriate target group, and the use of an alternative strategy for combining chemoradiotherapy should be explored in future trials.