bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractBackgroundThe 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.MethodsSix 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.ResultsAlthough 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).ConclusionThese 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

AbstractIn 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.
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

SummaryMany 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

BackgroundDespite several treatment options, adherence to therapy is poor in patients with bipolar disorder.AimsA double-blind, controlled comparison of aripiprazole and haloperidol in patients with bipolar I disorder experiencing acute manic or mixed episodes.MethodPatients (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.ResultsAt 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%).ConclusionsAripiprazole 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

BackgroundDespite extensive research and recommendations regarding the optimal prescription of antipsychotic drugs, polypharmacy and excessive dosing still prevail.AimsTo identify the factors associated with the polypharmacy and excessive dosing phenomena.MethodWe 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.ResultsPolypharmacy 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.ConclusionsEducational 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

BackgroundReliable, valid and easily administered screening instruments would greatly facilitate large-scale neuropsychiatric research.AimsTo test a parent telephone interview focused on autism-tics, attention-deficit hyperactivity disorder (ADHD) and other comorbidities (A-TAC).MethodParents 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.ResultsInterrater 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.ConclusionsThe 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

BackgroundThere 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.AimsThis 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.MethodUnivariate and multivariate analyses were conducted of data from questionnaires administered during pregnancy to a community sample of pregnant women.ResultsRecall 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.ConclusionsThere 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 MethodTo 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.ResultsFive 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 ImplicationsThe 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.
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.
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

PurposeConvincing 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 MethodsWe 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.ResultsThirty 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.ConclusionWe 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.