bluuebunny/crossref_metadata_2025 huggingface dataset:
Tracheal ring fracture and early tracheomalacia following percutaneous dilatational tracheostomy
Authors: Ho Eu Chin , Kapila Atul , Colquhoun-Flannery William
Published: August 2005

Background

Percutaneous dilatational tracheostomy (PDT) is increasingly popular within intensive care units for patients who need prolonged ventilatory support. Significant complications are rare.

Case presentation

Our patient suffered tracheal ring fracture and early tracheomalacia following this procedure. These complications are demonstrated in our accompanying video.

Conclusion

Contrary to common beliefs, tracheal rings are commonly fractured during the PDT procedure. The consequent granulation can lead to tracheal stenosis and tracheomalacia.
Automation of a problem list using natural language processing
Authors: Meystre Stephane , Haug Peter J
Published: August 2005

Background

The medical problem list is an important part of the electronic medical record in development in our institution. To serve the functions it is designed for, the problem list has to be as accurate and timely as possible. However, the current problem list is usually incomplete and inaccurate, and is often totally unused. To alleviate this issue, we are building an environment where the problem list can be easily and effectively maintained.

Methods

For this project, 80 medical problems were selected for their frequency of use in our future clinical field of evaluation (cardiovascular). We have developed an Automated Problem List system composed of two main components: a background and a foreground application. The background application uses Natural Language Processing (NLP) to harvest potential problem list entries from the list of 80 targeted problems detected in the multiple free-text electronic documents available in our electronic medical record. These proposed medical problems drive the foreground application designed for management of the problem list. Within this application, the extracted problems are proposed to the physicians for addition to the official problem list.

Results

The set of 80 targeted medical problems selected for this project covered about 5% of all possible diagnoses coded in ICD-9-CM in our study population (cardiovascular adult inpatients), but about 64% of all instances of these coded diagnoses. The system contains algorithms to detect first document sections, then sentences within these sections, and finally potential problems within the sentences. The initial evaluation of the section and sentence detection algorithms demonstrated a sensitivity and positive predictive value of 100% when detecting sections, and a sensitivity of 89% and a positive predictive value of 94% when detecting sentences.

Conclusion

The global aim of our project is to automate the process of creating and maintaining a problem list for hospitalized patients and thereby help to guarantee the timeliness, accuracy and completeness of this information.
Subjective assessments of comorbidity correlate with quality of life health outcomes: Initial validation of a comorbidity assessment instrument
Authors: Bayliss Elizabeth A , Ellis Jennifer L , Steiner John F
Published: September 2005

Background

Interventions to improve care for persons with chronic medical conditions often use quality of life (QOL) outcomes. These outcomes may be affected by coexisting (comorbid) chronic conditions as well as the index condition of interest. A subjective measure of comorbidity that incorporates an assessment of disease severity may be particularly useful for assessing comorbidity for these investigations.

Methods

A survey including a list of 25 common chronic conditions was administered to a population of HMO members age 65 or older. Disease burden (comorbidity) was defined as the number of self-identified comorbid conditions weighted by the degree (from 1 to 5) to which each interfered with their daily activities. We calculated sensitivities and specificities relative to chart review for each condition. We correlated self-reported disease burden, relative to two other well-known comorbidity measures (the Charlson Comorbidity Index and the RxRisk score) and chart review, with our primary and secondary QOL outcomes of interest: general health status, physical functioning, depression screen and self-efficacy.

Results

156 respondents reported an average of 5.9 chronic conditions. Median sensitivity and specificity relative to chart review were 75% and 92% respectively. QOL outcomes correlated most strongly with disease burden, followed by number of conditions by chart review, the Charlson Comorbidity Index and the RxRisk score.

Conclusion

Self-report appears to provide a reasonable estimate of comorbidity. For certain QOL assessments, self-reported disease burden may provide a more accurate estimate of comorbidity than existing measures that use different methodologies, and that were originally validated against other outcomes. Investigators adjusting for comorbidity in studies using QOL outcomes may wish to consider using subjective comorbidity measures that incorporate disease severity.
Neoadjuvant chemotherapy versus primary surgery in advanced ovarian carcinoma
Authors: Hegazy Mohamed AF , Hegazi Refaat AF , Elshafei Mohamed A , Setit Ahmed E , Elshamy Maged R , Eltatoongy Mohamed , Halim Amal AF
Published: August 2005

Background

Patients with advanced ovarian cancer should be treated by radical debulking surgery aiming at complete tumor resection. Unfortunately about 70% of the patients present with advanced disease, when optimal debulking can not be obtained, and therefore these patients gain little benefit from surgery. Neoadjuvant chemotherapy (NACT) has been proposed as a novel therapeutic approach in such cases. In this study, we report our results with primary surgery or neoadjuvant chemotherapy as treatment modalities in the specific indication of operable patients with advanced ovarian carcinoma (no medical contraindication to debulking surgery).

Patients and methods

A total of 59 patients with stage III or IV epithelial ovarian carcinomas were evaluated between 1998 and 2003. All patients were submitted to surgical exploration aiming to evaluate tumor resectability. Neoadjuvant chemotherapy was given (in 27 patients) where optimal cytoreduction was not feasible. Conversely primary debulking surgery was performed when we considered that optimal cytoreduction could be achieved by the standard surgery (32 patients).

Results

Optimal cytoreduction was higher in the NACT group (72.2%) than the conventional group (62.4%), though not statistically significant (P = 0.5). More important was the finding that parameters of surgical aggressiveness (blood loss rates, ICU stay and total hospital stay) were significantly lower in NACT group than the conventional group. The median overall survival time was 28 months in the conventional group and 25 months in NACT group with a P value of 0.5. The median disease free survival was 19 months in the conventional group and 21 months in NACT group (P = 0.4). In multivariate analysis, the pathologic type and degree of debulking were found to affect the disease free survival significantly. Overall survival was not affected by any of the study parameters.

Conclusion

Primary chemotherapy followed by interval debulking surgery in select group of patients doesn't appear to worsen the prognosis, but it permits a less aggressive surgery to be performed.
Transfer of efficient anti-melanocyte T cells from vitiligo donors to melanoma patients as a novel immunotherapeutical strategy
Authors: Palermo Belinda , Garbelli Silvia , Mantovani Stefania , Giachino Claudia
Published: August 2005

Background

Vitiligo is a relatively common progressive depigmentary condition that is believed to be due to the autoimmune-mediated loss of epidermal melanocytes. High frequencies of self-reactive T lymphocytes directed toward melanocyte differentiation antigens are found in vitiligo patients and might be directly responsible for the pathogenesis of the disease. An interesting aspect of vitiligo is its relation to melanoma: cytotoxic T lymphocytes directed to self antigens shared by normal melanocytes and melanoma cells are found in both conditions, but the resulting immune reactions are completely different. From this standpoint, the selective destruction of pigment cells that occurs in cases of vitiligo is the therapeutic goal sought in melanoma research.

Presentation of the hypothesis

Our working hypothesis is that vitiligo patients might represent a unique source of therapeutic cells to be used in allo-transfer for HLA-matched melanoma patients. The adoptive transfer ofex-vivogenerated autologous tumor-specific T cells is a therapy that has met with only limited success, essentially because of inability to isolate therapeutically valuable T cells from the majority of tumor patients. Ideally, model systems where strong and efficient responses against the same (tumor) antigens are achieved would represent a better source of therapeutic cells. We believe it is possible to identify one such model in the melanoma-vitiligo dichotomy: T lymphocytes specific for different melanocyte differentiation antigens are found in vitiligo and represent the effective anti-melanocyte reactivity that is often ineffective in melanoma.

Testing the hypothesis

Melanocyte-specific T cell clones can be isolated from the peripheral blood of vitiligo patients and tested for their capacity to efficiently expandin vitrowithout loosing their cytotoxic activity and to migrate to the skin. Cytotoxicity against melanoma patients' non-tumor cells can also be tested. In addition, it would be interesting to attempt an in vivo animal model. If the results obtained from these validation steps will be satisfactory, it might be possible to plan the clinical grade preparation of relevant clones for transfer.

Implications of the hypothesis

When translated into a clinical trial, the possibility ofin vitroselecting few effective tumor-specific T cell clones for infusion, inherent with this approach, could enhance the therapeutic graft-versus-tumor effect while possibly decreasing the risk of graft-versus-host disease.
Assessing observational studies of medical treatments
Authors: Hartz Arthur , Bentler Suzanne , Charlton Mary , Lanska Douglas , Butani Yogita , Soomro G Mustafa , Benson Kjell
Published: September 2005

Background

Previous studies have assessed the validity of the observational study design by comparing results of studies using this design to results from randomized controlled trials. The present study examined design features of observational studies that could have influenced these comparisons.

Methods

To find at least 4 observational studies that evaluated the same treatment, we reviewed meta-analyses comparing observational studies and randomized controlled trials for the assessment of medical treatments. Details critical for interpretation of these studies were abstracted and analyzed qualitatively.

Results

Individual articles reviewed included 61 observational studies that assessed 10 treatment comparisons evaluated in two studies comparing randomized controlled trials and observational studies. The majority of studies did not report the following information: details of primary and ancillary treatments, outcome definitions, length of follow-up, inclusion/exclusion criteria, patient characteristics relevant to prognosis or treatment response, or assessment of possible confounding. When information was reported, variations in treatment specifics, outcome definition or confounding were identified as possible causes of differences between observational studies and randomized controlled trials, and of heterogeneity in observational studies.

Conclusion

Reporting of observational studies of medical treatments was often inadequate to compare study designs or allow other meaningful interpretation of results. All observational studies should report details of treatment, outcome assessment, patient characteristics, and confounding assessment.
Association study of polymorphisms in synaptic vesicle-associated genes, SYN2 and CPLX2, with schizophrenia
Authors: Lee Hee Jae , Song Ji Young , Kim Jong Woo , Jin Sheng-Yu , Hong Mi Suk , Park Jin Kyoung , Chung Joo-Ho , Shibata Hiroki , Fukumaki Yasuyuki
Published: August 2005

Background

The occurrence of aberrant functional connectivity in the neuronal circuit is one of the integrative theories of the etiology of schizophrenia. Previous studies have reported that the protein and mRNA levels of the synapsin 2 (SYN2) and complexin 2 (CPLX2) genes were decreased in patients with schizophrenia. Synapsin 2 and complexin 2 are involved in synaptogenesis and the modulation of neurotransmitter release. This report presents a study of the association of polymorphisms ofSYN2andCPLX2with schizophrenia in the Korean population.

Methods

Six single nucleotide polymorphisms (SNPs) and one 5-bp insertion/deletion inSYN2and five SNPs inCPLX2were genotyped in 154 Korean patients with schizophrenia and 133 control patients using direct sequencing or restriction fragment length polymorphism analysis. An intermarker linkage disequilibrium map was constructed for each gene.

Results

Although there was no significant difference in the genotypic distributions and allelic frequencies of eitherSYN2orCPLX2polymorphisms between the schizophrenia and control groups, the two-way haplotype analyses revealed significant associations with the disease (P< 0.05 after Bonferroni correction). The three-way haplotype analyses also revealed a significant association ofSYN2with schizophrenia (P< 0.001 after Bonferroni correction).

Conclusion

These results suggest that bothSYN2andCPLX2may confer susceptibility to schizophrenia in the Korean population.
A computational method to predict genetically encoded rare amino acids in proteins
Authors: Chaudhuri Barnali N , Yeates Todd O
Published: August 2005

In several natural settings, the standard genetic code is expanded to incorporate two additional amino acids with distinct functionality, selenocysteine and pyrrolysine. These rare amino acids can be overlooked inadvertently, however, as they arise by recoding at certain stop codons. We report a method for such recoding prediction from genomic data, using read-through similarity evaluation. A survey across a set of microbial genomes identifies almost all the known cases as well as a number of novel candidate proteins.
A single-neuron PID adaptive multicontroller scheme based on RBFNN
Authors: Guo Bingjun , Yu Jinshou
Published: August 2005

In order to improve the control performance of the multicontroller proposed by Guo and Jutan (Canadian Journal of Chemical Engineering, 79, 817-22, 2001), a single-neuron PID multicontroller scheme based on a radial base function neural network (RBFNN) is proposed in this paper. This scheme has four controllers, specifically a set-point controller, two load controllers and a proportional controller. These controllers may be designed independently to achieve good control performance for both set-point tracking and load rejection. In particular, the set-point controller and the load controller have been chosen as single-neuron PID controllers. The model parameters and the parameters of the two single-neuron PID controller are updated in real time. For simplicity, the feedforward controller can be chosen as a unity gain proportional controller. It guarantees physical realizability and provides complete compensation for measurable disturbance. The simulation results show that the single-neuron PID adaptive multicontroller scheme based on RBFNN is very effective and the controller is of relatively strong robustness.
Teleoperated substitute robot with swing-type obstacle sensor
Authors: Takahashi Yoshihiko , Yatsumonji Takayoshi
Published: August 2005

A teleoperated substitute robot with a swing-type obstacle sensor is proposed in this paper. The teleoperated robot can, for example, act as a substitute for a child who is staying in a hospital room. Also, a person can take care of his/her elderly parents from overseas using the substitute robot. The two personal computers of the robot and an operator are connected using the Internet. Using a CCD camera, a speaker, a microphone and a PC display, both persons can communicate with each other. A swing-type obstacle sensor and an easy graphical human interface are proposed in order to ease the difficulties of remote operation. The design of the swing-type obstacle sensor has the advantage of cutting down the sensor numbers and the system cost. The system concept, the obstacle sensor, the human interface and some of the experimental results are presented. The validity of the robot system was confirmed by the application experiments with the assistance of a bedridden person.
Further considerations of defocus rangefinders
Authors: Whitehouse J. C.
Published: August 2005

This article follows a previous one that used a geometrical optics approach to analyse the operation of a defocus rangefinder system. In it, procedures were developed to enable range estimation to be made from width measurements of the blur profile when the temporally incoherent light source on the object was small and of unknown finite width. In this article, it is shown that the same procedures can be used for spatially incoherent monochromatic and quasi-monochromatic light sources in the presence of diffraction provided some constraints are met.
Emotional and physical health benefits of expressive writing
Authors: Baikie Karen A. , Wilhelm Kay
Published: August 2005

Writing about traumatic, stressful or emotional events has been found to result in improvements in both physical and psychological health, in non-clinical and clinical populations. In the expressive writing paradigm, participants are asked to write about such events for 15–20 minutes on 3–5 occasions. Those who do so generally have significantly better physical and psychological outcomes compared with those who write about neutral topics. Here we present an overview of the expressive writing paradigm, outline populations for which it has been found to be beneficial and discuss possible mechanisms underlying the observed health benefits. In addition, we suggest how expressive writing can be used as a therapeutic tool for survivors of trauma and in psychiatric settings.
Eye movement desensitisation and reprocessing: an update
Authors: Coetzee Rikus H. , Regel Stephen
Published: August 2005

Eye movement desensitisation and reprocessing (EMDR) is a relatively recent therapeutic approach to the treatment of traumatic memories in the wake of psychological trauma such as those found in post-traumatic stress disorder (PTSD). It is based on the theory that bilateral stimulation, mostly in the form of eye movements, allows the processing of traumatic memories. While the patient focuses on specific images, negative sensations and associated cognitions, bilateral stimulation is applied to desensitise the individual to these memories and more positive sensations and cognitions are introduced. Although there is still uncertainty about the theoretical concepts underlying EMDR and the role of bilateral stimulation, it is an effective and proven treatment for PTSD and traumatic memories. It should form part of treatment approaches offered to individuals with PTSD.
Anxiety disorders in people with learning disabilities
Authors: Cooray Sherva Elizabeth , Bakala Alina
Published: August 2005

People with learning disabilities are much more vulnerable to psychiatric illnesses, and will increasingly be accessing generic services. Treatment and management of psychiatric disorders is problematic, primarily because of difficulties in diagnosis, since classificatory systems are standardised on people with average intellectual functioning. This article provides an overview of the clinical implications of anxiety disorders within the context of learning disability.
Time for a shift in focus in schizophrenia: From narrow phenotypes to broad endophenotypes
Authors: Weiser Mark , van Os Jim , Davidson Michael
Published: September 2005

Many manifestations of mental illness, risk factors, course and even response to treatment are shared by several diagnostic groups. For example, cognitive and social impairments are present to some degree in most DSM and ICD diagnostic groups. The idea that diagnostic boundaries of mental illness, including schizophrenia, have to be redefined is reinforced by recent findings indicating that on the one hand multiple genetic factors, each exerting a small effect, come together to manifest as schizophrenia, and on the other hand, depending on interaction with the environment, the same genetic variations can present as diverse clinical phenotypes. Rather than attempting to find a unitary biological explanation for a DSM construct of schizophrenia, it would be reasonable to deconstruct it into the most basic manifestations, some of which are common with other DSM constructs, such as cognitive or social impairment, and then investigate the biological substrate of these manifestations.
Effectiveness of aripiprazole v. Haloperidol in acute bipolar mania
Authors: Vieta Eduard , Bourin Michel , Sanchez Raymond , Marcus Ronald , Stock Elyse , McQuade Robert , Carson William , Abou-Gharbia Neveen , Swanink Rene , Iwamoto Taro
Published: August 2005

Background

Despite several treatment options, adherence to therapy is poor in patients with bipolar disorder.

Aims

A double-blind, controlled comparison of aripiprazole and haloperidol in patients with bipolar I disorder experiencing acute manic or mixed episodes.

Method

Patients (n=347) were randomised to receive aripiprazole or haloperidol in this 12-week, multicentre study. The primary outcome measure was the number of patients in response (550% improvement from baseline in Young Mania Rating Scale score) and receiving therapy at week 12.

Results

At week 12, significantly more patients taking aripiprazole (49. 7%) were in response and receiving therapy compared with those taking haloperidol (28. 4%; P<0. 001). Continuation rates differed markedly between treatments (week 12: aripiprazole, 50. 9%; haloperidol, 29. 1%). Extrapyramidal adverse events were more frequent with haloperidol than aripiprazole (62. 7% v. 24. 0%).

Conclusions

Aripiprazole showed superior levels of response and tolerability to haloperidol in the treatment of an acute manic episode for up to 12 weeks.
Polypharmacy and excessive dosing: Psychiatrists' perceptions of antipsychotic drug prescription
Authors: Ito Hiroto , Koyama Asuka , Higuchi Teruhiko
Published: September 2005

Background

Despite extensive research and recommendations regarding the optimal prescription of antipsychotic drugs, polypharmacy and excessive dosing still prevail.

Aims

To identify the factors associated with the polypharmacy and excessive dosing phenomena.

Method

We studied 139 patients with schizophrenia, in 19 acute psychiatric units in Japanese hospitals, who were due to be discharged between October and December 2003. We examined patient characteristics, nurses' requests, and psychiatrists' characteristics and perceptions of prescribing practice and algorithms.

Results

Polypharmacy and excessive dosing were observed in 96 cases. Logistic regression analysis revealed that the use of multiple medications and excessive dosing were influenced by the psychiatrist's scepticism towards the use of algorithms, nurses' requests for more drugs and the patient's clinical condition.

Conclusions

Educational interventions are necessary for psychiatrists and nurses to follow evidence-based guidelines or algorithms.
Psychiatric telephone interview with parents for screening of childhood autism – tics, attention-deficit hyperactivity disorder and other comorbidities (A-TAC)
Authors: Hansson Sara Lina , Svanströmröjvall Annika , Rastam Maria , Gillberg Carina , Gillberg Christopher , Anckarsäter Henrik
Published: August 2005

Background

Reliable, valid and easily administered screening instruments would greatly facilitate large-scale neuropsychiatric research.

Aims

To test a parent telephone interview focused on autism-tics, attention-deficit hyperactivity disorder (ADHD) and other comorbidities (A-TAC).

Method

Parents of 84 children in contact with a child neuropsychiatric clinic and 27 control children were interviewed. Validity and interrater and test–retest reliability were assessed.

Results

Interrater and test–retest reliability were very good. Areas under receiver operating characteristics curves between interview scores and clinical diagnoses were around 0. 90 for ADHD and autistic spectrum disorders, and above 0. 70 for tics, learning disorders and developmental coordination disorder. Using optimal cut-off scores for autistic spectrum disorder and ADHD, good to excellent kappa levels for interviews and clinical diagnoses were noted.

Conclusions

The A–TAC appears to be a reliable and valid instrument for identifying autistic spectrum disorder, ADHD, tics, learning disorders and developmental coordination disorder.
Early experiences and their relationship to maternal eating disorder symptoms, both lifetime and during pregnancy
Authors: Senior R. , Barnes J. , Emberson J. R. , Golding J.
Published: September 2005

Background

There is some evidence that early sexual abuse is an aetiological factor for eating disorder. However, there is sparse information from large-scale, non-clinical studies.

Aims

This study was designed to explore which early experiences, recalled during pregnancy, were associated with both lifetime and antenatal eating disorder symptoms in a community sample.

Method

Univariate and multivariate analyses were conducted of data from questionnaires administered during pregnancy to a community sample of pregnant women.

Results

Recall of parental mental health problems and of early unwanted sexual experiences were independently associated with both lifetime eating problems, laxative use and vomiting during pregnancy, and marked concern during pregnancy over shape and weight.

Conclusions

There are public health implications for these results. Eating disorders in mothers represent a risk for child development. It may be important to enquire during pregnancy about a history of eating problems and to provide the opportunity for early experiences to be discussed.
Development and evaluation of a screening tool for identifying prisoners with severe mental illness
Authors: Birmingham Luke , Mullee Mark
Published: September 2005

Aims and Method

To develop and evaluate a screening tool based on the observational skills of prison officers to identify adult male prisoners with severe mental illness. The tool was developed from open-ended interviews with officers and diagnostic interviews with prisoners. A case–comparison study was used to evaluate the tool. Fifty prisoners identified using the tool and 50 randomly selected prisoners underwent diagnostic interviews to determine the proportion in each group with severe mental illness.

Results

Five behavioural indicators of severe mental illness were identified and incorporated into the tool. In the evaluation, 19 out of 50 (38%) of the cases identified were found to have severe mental illness compared with none in the comparison group.

Clinical Implications

The simple tool shows promise for the identification of prisoners with severe mental illness by prison officers. It does require further evaluation in other prison settings.
Tsunami psychiatry
Authors: Kua Heok , Iskandar Yul
Published: September 2005

We report a conference to discuss the mental health response to the recent tsunami disaster that struck the coasts of the Indian Ocean on 26 December 2004. The conference was convened in Jakarta on 3–5 February 2005 and was organised by the Indonesian Society for Biological Psychiatry and chaired by Dr Yul Iskandar. The meeting brought together the Asian psychiatrists who helped out in the disaster zones in Aceh and Meulaboh (Indonesia), Penang (Malaysia) and Phuket (Thailand). The experiences shared by these psychiatrists have important implications for the future training of psychiatrists, especially those from developing countries.
Proteasome Inhibition With Bortezomib (PS-341): A Phase I Study With Pharmacodynamic End Points Using a Day 1 and Day 4 Schedule in a 14-Day Cycle
Authors: Hamilton A.L. , Eder J.P. , Pavlick A.C. , Clark J.W. , Liebes L. , Garcia-Carbonero R. , Chachoua A. , Ryan D.P. , Soma V. , Farrell K. , Kinchla N. , Boyden J. , Yee H. , Zeleniuch-Jacquotte A. , Wright J. , Elliott P. , Adams J. , Muggia F.M.
Published: August 2005

Purpose

We performed a phase I study of a day (D) 1 and D4 bortezomib administration once every 2 weeks to determine the recommended phase II dose and toxicity profile, and the extent of 20S proteasome inhibition obtained.

Patients and Methods

Patients with solid tumors or lymphomas were treated with bortezomib at 0.25 to 1.9 mg/m2 on D1 and D4, every 2 weeks. 20S proteasome levels in blood were assayed at baseline and at 1, 4, and 24 hours postdose in cycle 1.

Results

On this D1 and D4 every 2 weeks' schedule, dose-limiting toxicity (DLT) was evident at the 1.75 and 1.9 mg/m2 dose levels, most commonly in patients receiving individual total doses ≥ 3.0 mg. The main DLT was peripheral neuropathy evident at the higher doses and in patients previously exposed to neurotoxic agents. Other DLTs included diarrhea and fatigue; grade 3 thrombocytopenia was also noted. Reversible inhibition of 20S proteasome activity was dose dependent and best fit a total dose (mg) per fraction rather than mg/m2; 70% of baseline activity was inhibited by a dose of 3.0 to 3.5 mg given on D1 and on D4 every other week. Antitumor effects short of confirmed partial responses were observed in patients with melanoma, non–small-cell lung cancer, and renal cell carcinoma.

Conclusion

Bortezomib (PS-341) is a novel antineoplastic agent that is well tolerated at doses not exceeding 3.0 mg (equivalent to 1.75 mg/m2), repeated on D1 and D4 every other week. This dose correlates with 70% inhibition of 20S proteasome activity. DLTs include neuropathy, fatigue, and diarrhea.
Preoperative PSA Velocity Is an Independent Prognostic Factor for Relapse After Radical Prostatectomy
Authors: Patel Deep A. , Presti Joseph C. , McNeal John E. , Gill Harcharan , Brooks James D. , King Christopher R.
Published: August 2005

Purpose

Preoperative prostate-specific antigen (PSA) velocity (PSAV), or the rate of PSA rise before diagnosis, predicts for risk of cancer death after radical prostatectomy (RP). We evaluated the relative merit of established preoperative factors, including biopsy indices and preoperative PSAV, for their impact on relapse after RP.

Patients and Methods

The outcomes of 202 men who underwent RP were reviewed. Biopsies were characterized for grade, percentage positive cores, and total linear tumor length. Surgical specimens were characterized for cancer volume, relative percentage by grade, extracapsular extension, and margin status. Univariate and multivariate analyses were performed with respect to relapse-free survival after RP.

Results

Thirty-one patients relapsed after RP (defined as PSA ≥ 0.2 ng/mL), with a median time to failure of 16 months. Median follow-up was 48 months. Kaplan-Meier relapse-free survival at 5 years was 89%, compared with 73% for PSAV ≤ 2 v > 2 ng/mL/year (P = .003). On multivariate analysis, only the biopsy Gleason sum (P < .008; relative risk, > 4.8) and the preoperative PSAV (P < .04; relative risk, 3.0 to 4.7) remained significant. Patients with a PSAV of > 2 ng/mL/year were more likely to be pT3 (P = .007), have positive margins (P = .01), have tumors > 1 mL (P = .05), and possess > 10% grade 4/5 tumors (P = .04).

Conclusion

The preoperative PSAV is a significant independent clinical factor predicting for relapse after RP and also predicts for larger, more aggressive, and more locally advanced tumors. Its inclusion will be useful in risk stratification, evaluation for alternatives to surgery, and patient selection for neoadjuvant or adjuvant therapies as part of randomized clinical trials.
Randomized Controlled Trial of an Educational Intervention for Managing Fatigue in Women Receiving Adjuvant Chemotherapy for Early-Stage Breast Cancer
Authors: Yates Patsy , Aranda Sanchia , Hargraves Maryanne , Mirolo Bev , Clavarino Alexandra , McLachlan SueAnne , Skerman Helen
Published: August 2005

Purpose

To evaluate the efficacy of a psychoeducational intervention in improving cancer-related fatigue.

Patients and Methods

This randomized controlled trial involved 109 women commencing adjuvant chemotherapy for stage I or II breast cancer in five chemotherapy treatment centers. Intervention group patients received an individualized fatigue education and support program delivered in the clinic and by phone over three 10- to 20-minute sessions 1 week apart. Instruments included a numeric rating scale assessing confidence with managing fatigue; 11-point numeric rating scales measuring fatigue at worst, average, and best; the Functional Assessment of Cancer Therapy–Fatigue and Piper Fatigue Scales; the Cancer Self-Efficacy Scale; the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30; and the Hospital Anxiety and Depression Scale. For each outcome, separate analyses of covariance of change scores between baseline (T1) and the three follow-up time points (T2, T3, and T4) were conducted, controlling for the variable's corresponding baseline value.

Results

Compared with the intervention group, mean difference scores between the baseline (T1) and immediate after the test (T2) assessments increased significantly more for the control group for worst and average fatigue, Functional Assessment of Cancer Therapy–Fatigue, and Piper fatigue severity and interference measures. These differences were not observed between baseline and T3 and T4 assessments. No significant differences were identified for any pre- or post-test change scores for confidence with managing fatigue, cancer self-efficacy, anxiety, depression, or quality of life.

Conclusion

Preparatory education and support has the potential to assist women to cope with cancer-related fatigue in the short term. However, further research is needed to identify ways to improve the potency and sustainability of psychoeducational interventions for managing cancer-related fatigue.
Durable Clinical, Cytogenetic, and Molecular Remissions After Allogeneic Hematopoietic Cell Transplantation for Refractory Sezary Syndrome and Mycosis Fungoides
Authors: Molina Arturo , Zain Jasmine , Arber Daniel A. , Angelopolou Maria , O’Donnell Margaret , Murata-Collins Joyce , Forman Stephen J. , Nademanee Auayporn
Published: August 2005

Purpose

Sezary syndrome (SS) and tumor-stage mycosis fungoides (MF) are generally incurable with currently available treatments. We conducted a retrospective study to evaluate the outcome of allogeneic hematopoietic stem-cell transplantation (HSCT) in this patient population.

Patient and Methods

From August 1996 through October 2002, eight patients with advanced MF/SS underwent allogeneic HSCT at our institution. All patients were heavily pretreated, having failed a median number of seven prior therapies (range, five to 12). Clonal T-cell populations in peripheral blood or bone marrow were detectable by polymerase chain reaction analyses of T-cell receptor γ-chain gene rearrangements in six patients and cytogenetics in three patients. The conditioning regimen included total-body irradiation and cyclophosphamide (n = 3), busulfan and cyclophosphamide (n = 1), and the reduced-intensity regimen of fludarabine and melphalan (n = 4). Allogeneic hematopoietic stem cells were obtained from HLA-matched siblings (n = 4) and unrelated donors (n = 4).

Results

All patients achieved complete clinical remission and resolution of molecular and cytogenetic markers of disease within 30 to 60 days after HSCT. Two patients died from transplantation-related complications; graft-versus-host disease (GVHD; n = 1) and respiratory syncytial virus pneumonia (n = 1). With a median follow-up of 56 months, six patients remain alive and without evidence of lymphoma.

Conclusion

Our results suggest that allogeneic HSCT from both HLA–matched sibling and unrelated donors can induce durable clinical, molecular, and cytogenetic remissions in patients with advanced cutaneous T-cell lymphoma that is refractory to standard therapies.
Current Management of Brain Metastases, With a Focus on Systemic Options
Authors: Langer Corey J. , Mehta Minesh P.
Published: August 2005

Brain metastases are an important sequelae of many types of cancer, most commonly lung cancer. Current treatment options include whole-brain radiation therapy (WBRT), surgical resection, stereotactic radiosurgery, and chemotherapy. Corticosteroids and antiepileptic medications are commonly used for palliation of mass effect and seizures, respectively. The overall median survival is only 4 months after WBRT. Combined-modality strategies of WBRT with either chemotherapy or novel anticancer agents are under clinical investigation. Promising results have been obtained with several experimental agents and confirmatory phase III trials are underway. Although improvement in overall survival has not been seen universally, reduction in death due to progression of brain metastases and prolongation of the time to neurologic and neurocognitive progression have been reported in selected series. On the basis of these findings, it might be possible to identify new agents that may enhance the efficacy of WBRT.
Study of Etanercept, a Tumor Necrosis Factor-Alpha Inhibitor, in Recurrent Ovarian Cancer
Authors: Madhusudan Srinivasan , Muthuramalingam Sethupathi R. , Braybrooke Jeremy P. , Wilner Susan , Kaur Kulwinder , Han Cheng , Hoare Susan , Balkwill Frances , Ganesan Trivadi S.
Published: August 2005

Purpose

Convincing data support the link between inflammation and ovarian cancer. Tumor necrosis factor-alpha (TNF-α), a major mediator of inflammation, is chronically produced in the ovarian tumor microenvironment and may enhance tumor growth and invasion by inducing the secretion of cytokines, proangiogenic factors, and metalloproteinases. Etanercept is a recombinant human soluble p75 TNF receptor that binds to TNF-α and renders it biologically unavailable. In the current study, we sought to determine the toxicity, biologic activity, and therapeutic efficacy of etanercept in recurrent ovarian cancer.

Patients and Methods

We initiated a phase I-B, nonrandomized, open-label study in patients with recurrent ovarian cancer. Etanercept was administered subcutaneously at a dose of 25 mg twice weekly (cohort one) and 25 mg thrice weekly (cohort two) until disease progression.

Results

Thirty patients were recruited (cohort one, 17 patients; cohort two, 13 patients). Eighteen of the 30 patients (cohort one, 11 patients; cohort two, seven patients) completed ≥ 12 weeks of treatment. Six patients achieved prolonged disease stabilization (cohort one, two patients [40 and 25 weeks]; cohort two, four patients [34, 24, 22, and 24 weeks]). A significant rise in immunoreactive TNF was seen in all patients (pretreatment compared with end of treatment). A phytohemagglutinin-stimulated whole-blood cytokine assay showed a significant fall in interleukin-6 (cohort one [11 of 17]) and CCL2 (cohort one [13 of 17]) levels. Common adverse effects were injection-site reactions and fatigue.

Conclusion

We provide evidence for the biologic activity and safety of etanercept in recurrent ovarian cancer. Our data suggest possible clinical activity that must be confirmed in future studies.
Prospective Multicenter Validation of the Independent Prognostic Value of the Mitotic Activity Index in Lymph Node–Negative Breast Cancer Patients Younger Than 55 Years
Authors: Baak Jan P.A. , van Diest Paul J. , Voorhorst Feja J. , van der Wall Elsken , Beex Louk V.A.M. , Vermorken Jan B. , Janssen Emiel A.M.
Published: August 2005

Purpose

To validate the independent strong prognostic value of mitotic activity index (MAI) in lymph node (LN) –negative invasive breast cancer patients younger than 55 years in a nationwide multicenter prospective study.

Patients and Methods

Analysis of routinely assessed MAI and other prognosticators in 516 patients (median follow-up, 118 months; range, 8 to 185 months), without systemic adjuvant therapy or previous malignancies.

Results

Distant metastases occurred in 127 patients (24.6%); 90 (17.4%) died as a result of metastases. MAI (< 10, ≥ 10) showed strong association with recurrence (hazard ratio [HR], 3.12; 95% CI, 2.17 to 4.50; P ≤ .0001) and mortality (HR, 4.42; 95% CI, 2.79 to 7.01; P < .0001). The absolute difference in 10-year Kaplan-Meier estimates of time to distant recurrence as well as survival was 22% between MAI less than 10 versus ≥ 10. This effect was independent of age, estrogen receptor (ER) status, and tumor diameter (which were significant prognosticators). In multivariate analysis with regard to patient age, tumor diameter, grade, ER status, and the St Gallen criterion, MAI proved to be an independent and the strongest prognosticator. Tubular formation (TF) and nuclear atypia (NA), as constituents of (expert revised) grade, had no (for TF) or limited (for NA, P = .048) additional prognostic value to the MAI. In the group with MAI less than 10, MAI less than 3 versus more than 3 had additional value but the classical threshold of 0 to 5 v 6 to 10 did not. With this additional subdivision of MAI as less than 3, 3 to 9, and more than 9, NA lost its additive prognostic value.

Conclusion

The MAI is the strongest, most widely available, easily assessable, inexpensive, well-reproducible prognosticator and is well suited to routinely differentiate between high- and low-risk LN-negative breast cancer patients younger than 55 years.
Prognostic Factors in Advanced Cancer Patients: Evidence-Based Clinical Recommendations—A Study by the Steering Committee of the European Association for Palliative Care
Authors: Maltoni Marco , Caraceni Augusto , Brunelli Cinzia , Broeckaert Bert , Christakis Nicholas , Eychmueller Steffen , Glare Paul , Nabal Maria , Viganò Antonio , Larkin Philip , De Conno Franco , Hanks Geoffrey , Kaasa Stein
Published: August 2005

Purpose

To offer evidence-based clinical recommendations concerning prognosis in advanced cancer patients.

Methods

A Working Group of the Research Network of the European Association for Palliative Care identified clinically significant topics, reviewed the studies, and assigned the level of evidence. A formal meta-analysis was not feasible because of the heterogeneity of published studies and the lack of minimal standards in reporting results. A systematic electronic literature search within the main available medical literature databases was performed for each of the following four areas identified: clinical prediction of survival (CPS), biologic factors, clinical signs and symptoms and psychosocial variables, and prognostic scores. Only studies on patients with advanced cancer and survival ≤ 90 days were included.

Results

A total of 38 studies were evaluated. Level A evidence-based recommendations of prognostic correlation could be formulated for CPS (albeit with a series of limitations of which clinicians must be aware) and prognostic scores. Recommendations on the use of other prognostic factors, such as performance status, symptoms associated with cancer anorexia-cachexia syndrome (weight loss, anorexia, dysphagia, and xerostomia), dyspnea, delirium, and some biologic factors (leukocytosis, lymphocytopenia, and C-reactive protein), reached level B.

Conclusion

Prognostication of life expectancy is a significant clinical commitment for clinicians involved in oncology and palliative care. More accurate prognostication is feasible and can be achieved by combining clinical experience and evidence from the literature. Using and communicating prognostic information should be part of a multidisciplinary palliative care approach.
Salvage Therapy of Progressive and Recurrent Hodgkin’s Disease: Results From a Multicenter Study of the Pediatric DAL/GPOH-HD Study Group
Authors: Schellong Günther , Dörffel Wolfgang , Claviez Alexander , Körholz Dieter , Mann Georg , Scheel-Walter Hans-G. , Bökkerink Jos P.M. , Riepenhausen Marianne , Lüders Heike , Pötter Richard , Rühl Ursula
Published: August 2005

Purpose

To evaluate a salvage therapy (ST-HD-86) for patients with progressive and relapsed Hodgkin’s disease after primary treatment in the pediatric DAL/GPOH studies. The essential chemotherapeutic regimens were ifosfamide, etoposide, and prednisone (IEP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

Methods

One hundred seventy-six patients with progression (n = 51) or first relapse (n = 125) were enrolled by 67 centers. The median time from initial diagnosis to progression/relapse was 1.1 year (range, 0.1 to 15.3 years), and the patients’ median age was 14.7 years (range, 4.3 to 24.5 years). Salvage chemotherapy consisted of two to three cycles of IEP alternating with one to two cycles of ABVD supplemented in part by one to two cycles of cyclophosphamide, vincristine, procarbazine, and prednisone or lomustine (CCNU), etoposide, and prednimustine. Radiotherapy was given to involved areas using individualized doses. In the 1990s, additional high-dose chemotherapy with autologous stem-cell transplantation (SCT) was introduced for patients with unfavorable prognosis.

Results

Disease-free survival (DFS) and overall survival (OS) after 10 years are 62% and 75%, respectively (SE, 4% each). Of 176 patients, 73 suffered second events. The risk-factor analysis revealed the time to progression/relapse as the strongest prognostic factor (P = .0001). Patients with progression have an inferior outcome (DFS, 41%; OS, 51%), whereas patients with late relapse (> 12 months after end of therapy) do well (DFS, 86%; OS, 90%), although none of them received SCT in second remission.

Conclusion

The result can be considered favorable. Whereas the salvage strategy for progressive disease has to be optimized further, it is possible to reduce intensity and avoid SCT in late relapses after Hodgkin’s disease in childhood/adolescence.
Survival in Patients Operated on for Pathologic Fracture: Implications for End-of-Life Orthopedic Care
Authors: Nathan Saminathan S. , Healey John H. , Mellano Danilo , Hoang Bang , Lewis Isobel , Morris Carol D. , Athanasian Edward A. , Boland Patrick J.
Published: August 2005

Purpose

Life expectancy is routinely used as part of the decision-making process in deciding the value of surgery for the treatment of bone metastases. We sought to investigate the validity of frequently used indices in the prognostication of survival in patients with metastatic bone disease.

Methods

The study prospectively assessed 191 patients who underwent surgery for metastatic bone disease. Diagnostic, staging, nutritional, and hematologic parameters cited to be related to life expectancy were evaluated. Preoperatively, the surgeon recorded an estimate of projected life expectancy for each patient. The time until death was recorded.

Results

Kaplan-Meier survival analyses indicated that the survival estimate, primary diagnosis, use of systemic therapy, Eastern Cooperative Oncology Group (ECOG) performance status, number of bone metastases, presence of visceral metastases, and serum hemoglobin, albumin, and lymphocyte counts were significant for predicting survival (P < .004). Cox regression analysis indicated that the independently significant predictors of survival were diagnosis (P < .006), ECOG performance status (P < .04), number of bone metastases (P < .008), presence of visceral metastases (P < .03), hemoglobin count (P < .009), and survival estimate (P < .00005). Diagnosis, ECOG performance status, and visceral metastases covaried with surgeon survival estimate. Linear regression and receiver-operator characteristic assessment confirmed that clinician estimation was the most accurate predictor of survival, followed by hemoglobin count, number of visceral metastases, ECOG performance status, primary diagnosis, and number of bone metastases. Nevertheless, survival estimate was accurate in predicting actual survival in only 33 (18%) of 181 patients.

Conclusion

A better means of prognostication is needed. In this article, we present a sliding scale for this purpose.