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Renal cell carcinoma: review of novel single-agent therapeutics and combination regimens.

A search of the Medline database and ASCO 2003 conference proceedings was conducted to identify clinical trials currently underway using single-agent therapy for renal cell carcinoma (RCC). Combination trials were identified using the ASCO 2003 conference proceedings. Fourteen single-agent therapies employing different mechanisms of action were identified in the published literature: imatinib mesylate (Gleevec); bevacizumab (Avastin); thalidomide (Thalomid); gefitinib (ZD1839) (Iressa); cetuximab (IMC-C225) (Erbitux); bortezomib (PS-341) (Velcade); HSPPC-96 (Oncophage); BAY 59-8862; ABT-510; G250; CCI-779; SU5416; PTK/ZK; and ABX-EGF. Six distinct fields of clinical research have emerged: monoclonal antibodies, small molecules, vaccines, second-generation taxanes, nonapeptides and immunomodulators. Five combination regimens, primarily biological response modifiers (interleukin-2 or interferon-alpha), chemotherapy- or thalidomide-based, were identified. All therapies demonstrated acceptable toxicity profiles. Clinical benefit was assessed based on each study's reported criteria: antitumor response (regression or stability) ranged from 5% to 71%. In the past several years, significant advances in the underlying biological mechanisms of RCC, particularly the role of tumor angiogenesis, have permitted the design of molecularly targeted therapeutics. Based on preliminary and limited studies, combination therapies offer the greatest clinical benefit in the management of this malignancy, although additional basic research is still warranted.

Antibodies, Monoclonal↗

Cognitive dysfunctions in schizophrenia: potential benefits of cholinesterase inhibitor adjunctive therapy.

OBJECTIVE: In schizophrenia, cognitive dysfunctions commonly affect attention, memory and executive function, interfere with functional outcome and remain difficult to treat. Previous studies have implicated the cholinergic system in cognitive functioning. In Alzheimer's disease, cholinergic agonists have shown modest clinical benefits on cognitive and behavioural symptoms. Impaired cholinergic activity might also be involved in schizophrenia. Hence the role of cholinesterase inhibitors (ChEI) as adjunctive therapy is under study. We aimed to review the literature and evaluate the overall effectiveness of ChEI adjunctive therapy for the management of cognitive dysfunctions in schizophrenia. METHODS: We conducted a computer-based search using PubMed (up to February 15, 2006) and ISI Web of Science (conference proceeding abstracts from January 2003 to December 2005) databases. We used the search terms "schizophrenia," "cognition or memory" and "tacrine or donepezil or rivastigmine or galantamine." Studies included were critically analyzed for allocation, blindness, duration and study design, demographic data, and clinical and neuropsychological outcome assessments. We excluded studies that involved patients with psychiatric disorders other than schizophrenia-spectrum or if they involved animals or molecular investigations. We also excluded conference proceeding abstracts with no explicit neuropsychological battery and/or results. RESULTS: Data on ChEI as adjunctive therapy for the cognitive impairments in schizophrenia are sparse and so far derived from small samples and mostly open uncontrolled studies. ChEI's potential in long-term management has barely been documented and remains to be fully explored. CONCLUSION: There is insufficient evidence on whether ChEI should be used for the treatment of cognitive dysfunctions in schizophrenia. Nevertheless, further studies with appropriate trial designs and outcome measures in homogenous schizophrenia populations are warranted.

Cholinesterase Inhibitors↗

The effectiveness of hospital pharmacy in the UK: methodology for finding the evidence.

OBJECTIVE: To describe the methodology used to identify United Kingdom (UK) hospital pharmacy practice research work from the last two decades. METHOD: A comprehensive search for citations that appeared to contribute to the overall evidence or in some way measure, demonstrate or evaluate the effectiveness of UK hospital pharmacy practice. This involved a search of thirteen electronic databases covering a wide variety of UK, European and international publications, hand searching of selected UK journals and conference proceedings, a written request for details sent to all UK Chief Pharmacists and Directors of Pharmacy and a bibliography search of each reference identified. All appropriate references were then added to a single computer database. MAIN OUTCOME MEASURE: Number of references identified by each strand of the search strategy. RESULTS: The search initially highlighted a total of 10,099 articles from the thirteen reference databases, but only 281 were considered suitable for inclusion in the final review. Hand searching of the selected journals and conference proceedings yielded another 173 references and the written requests to hospital chief pharmacists resulted in another 128 references being identified. Finally, bibliography searches of the articles identified by the above three methods resulted in another 242 references, bringing the total number of references to 824. CONCLUSION: This paper describes a strategy to identify a comprehensive collection of citations supporting the evidence for the effectiveness of hospital pharmaceutical services in the UK. The large number of references identified demonstrate that hospital pharmacists in the UK make significant contributions to both the research literature and to patient care. However, database searches alone highlighted just 34% of the total references finally included in this study, demonstrating that pharmacy practice research work may be difficult to access by conducting database searches alone. The results from this project provide a resource for the profession and can be utilised as a foundation for future developments in both the delivery and research of hospital pharmacy practice.

Databases, Factual↗

Partial liquid ventilation for the prevention of mortality and morbidity in paediatric acute lung injury and acute respiratory distress syndrome.

BACKGROUND: Acute lung injury, and acute respiratory distress syndrome, are syndromes of severe respiratory failure. Children with acute lung injury or acute respiratory syndrome have high mortality and significant morbidity. Partial liquid ventilation is proposed as a less injurious form of respiratory support for these children. Uncontrolled studies in adults have shown improvement in gas exchange and lung compliance with partial liquid ventilation A single uncontrolled study in six children with acute respiratory syndrome showed some improvement in gas exchange during three hours of partial liquid ventilation. OBJECTIVES: To assess whether partial liquid ventilation reduces either mortality or morbidity, or both, in children with acute lung injury or acute respiratory syndrome. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library issue 2, 2003; MEDLINE (1966 to April 2003); and CINAHL (1982 to April 2003); intensive care journals and conference proceedings; reference lists and 'grey literature'. SELECTION CRITERIA: Randomized controlled trials which compared partial liquid ventilation with other forms of ventilation, in children (28 days - 18 years) with acute lung injury or acute respiratory syndrome, reporting one or more of the following: mortality; duration of mechanical ventilation, respiratory support, oxygen therapy, stay in the intensive care unit, or stay in hospital; infection; or long term cognitive impairment or neurodevelopmental progress or other long term morbidities. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated the quality of the relevant studies and extracted the data from the included studies. MAIN RESULTS: Only one study enrolling 182 patients (only reported as an abstract in conference proceedings) was identified and found eligible for inclusion: the authors report only limited results. The trial was stopped prematurely and therefore under-powered to detect any significant differences. The only outcome of clinical significance available was 28 day mortality: there was no statistically significant difference between groups with a relative risk for 28 day mortality in the partial liquid ventilation group of 1.54 (95% confidence intervals of 0.82 to 2.9). REVIEWERS' CONCLUSIONS: There is no evidence from randomized controlled trials to support or refute the use of partial liquid ventilation in children with acute lung injury or acute respiratory syndrome: adequately powered, high quality randomized controlled trials are still needed to assess its efficacy. Clinically relevant outcome measures should be assessed (mortality at discharge and later, duration of respiratory support and hospital stay, and long-term neurodevelopmental outcomes) and the studies should be published in full.

Adolescent↗

Inhaled nitric oxide for acute hypoxemic respiratory failure in children and adults.

OBJECTIVES: To determine the effect of iNO, compared with inhaled placebo, on outcome in AHRF in children and/or adults. SEARCH STRATEGY: Randomised controlled trials (RCT's) were identified from electronic databases; MEDLINE, EMBASE, the Cochrane Library, and CINAHL, as well as from bibliographies of retrieved articles. Relevant journals and conference proceedings were hand searched and authors published in this field were contacted for knowledge of unpublished ongoing trials. SELECTION CRITERIA: RCT's comparing iNO with maximal conventional therapy and inhaled placebo, for AHRF in either children or adults. DATA COLLECTION AND ANALYSIS: Data were extracted and the analyses performed independently by two reviewers. All 5 authors were contacted for missing data. Qualitative assessment of each trial was made according to methodology described by Schulz (Schulz 1995), and analyses according to statistical methods in Review Manager MetaView 3.1. The fixed effect model was applied. Where possible, sub-group analyses were performed to assess the impact of iNO in varied doses. MAIN RESULTS: Five RCT's were evaluated, assessing 535 patients with AHRF. Inhaled nitric oxide made no impact on mortality in trials without cross-over (RR 0.98, 95%CI 0.66, 1.44), or with cross-over of treatment failures to open-label iNO (RR 1.22, 95%CI 0.65, 2.29). Published evidence from one study demonstrated that iNO resulted in a transient improvement in oxygenation in the first 24 hours of treatment: the oxygenation index (OI) showed a mean difference of -3 [95% CI -5.354, -0.646], and PaO2/FiO2 ratio, a mean difference of 35 [95% CI 20.236, 49.764]. Limited data demonstrated no difference in ventilator-free days between treatment and placebo groups, and no specific dose of iNO was significantly advantageous over another. Other clinical indicators of effectiveness, such as duration of hospital and intensive care stay, were inconsistently reported. There were no complications reported to be directly attributable to this treatment. REVIEWER'S CONCLUSIONS: From the data provided to date, iNO had no effect on mortality and only transiently improved oxygenation in AHRF in children and/or adults. There was a lack of data to assess other end points. The long term adverse effects of this drug are not known, as no long term follow-up of trial participants has been reported. If further trials comparing iNO with an inhaled placebo are to proceed, they should be stratified for primary disease and must specifically evaluate clinically relevant outcomes, before any benefit of iNO in AHRF can be excluded.

Acute Disease↗

Nursing record systems: effects on nursing practice and health care outcomes.

BACKGROUND: A nursing record system is the record of care planned and/or given to individual patients/clients by qualified nurses or other caregivers under the direction of a qualified nurse. Nursing record systems may be an effective way of influencing nurse practice. OBJECTIVES: To assess the effects of nursing record systems on nursing practice and patient outcomes. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, Cinahl, Sigle, and databases of the Royal College of Nursing, King's Fund, the NHS Centre for Reviews and Dissemination, and the Institute of Electrical Engineers up to August 1999; and OCLC First Search, Department of Health database, NHS Register of Computer Applications and the Health Visitors' Association database up to the end of 1995. We hand searched the Journal of Nursing Administration (1971-1999), Computers in Nursing (1984-1999), Information Technology in Nursing (1989-1999) and reference lists of articles. We also hand searched the major health informatics conference proceedings. We contacted experts in the field of nursing informatics, suppliers of nursing computer systems, and relevant Internet groups. SELECTION CRITERIA: Randomised trials, controlled before and after studies and interrupted time series comparing one kind of nursing record system with another, in hospital, community or primary care settings. The participants were qualified nurses, students or health care assistants working under the direction of a qualified nurse and patients receiving care recorded and/or planned using nursing record systems. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Six trials involving 1407 people were included. In three studies of client held records, there were no overall positive or negative effects, although some administrative benefits through fewer missing notes were suggested. A paediatric pain management sheet study showed a positive effect on the children's pain intensity. A computerised nursing care planning study showed a negative effect on documented nursing care planning. A controlled before-and-after study of two paper nursing record systems showed improvement in meeting documentation standards. REVIEWER'S CONCLUSIONS: No evidence was found of effects on practice attributable to changes in record systems. Although there is a paucity of studies of sufficient methodological rigour to yield reliable results in this area, it is clear from the literature that it is possible to set up randomised trials or other quasi-experimental designs needed to produce evidence for practice. The research undertaken so far may have suffered both from methodological problems and faulty hypotheses.

Humans↗

Palliative radiotherapy regimens for non-small cell lung cancer.

BACKGROUND: Palliative radiotherapy (RT) to the chest is often used in patients with lung cancer, but RT regimens are more often based on tradition than research results. OBJECTIVES: To discover the most effective and least toxic regimens of palliative RT, and whether higher doses increase survival. SEARCH STRATEGY: Electronic databases, reference lists, handsearching of journals and conference proceedings, and discussion with experts were used to identify potentially eligible trials, published and unpublished. SELECTION CRITERIA: Randomised controlled clinical trials comparing different regimens of palliative RT in patients with non-small lung cancer. DATA COLLECTION AND ANALYSIS: Ten randomised trials were reviewed. There were important differences in the doses of RT investigated, the patient characteristics and the outcome measures. Because of this heterogeneity no meta-analysis was attempted. MAIN RESULTS: There is no strong evidence that any regimen gives greater palliation. Higher dose regimens give more acute toxicity. There is evidence for a modest increase in survival (6% at 1 year and 3% at 2 years) in patients with better performance status (PS) given higher dose RT. REVIEWER'S CONCLUSIONS: The majority of patients should be treated with short courses of palliative RT, of 1 or 2 fractions. Care should be taken with the dose to the spinal cord. The use of high dose palliative regimens should be considered for and discussed with selected patients with good PS. More research is needed into reducing the acute toxicity of large fraction regimens and into the role of radical compared to high dose palliative RT and more homogeneous studies are needed.

Carcinoma, Non-Small-Cell Lung↗

Conservative management of post prostatectomy incontinence.

BACKGROUND: Urinary incontinence after prostatectomy is a common problem. Conservative management of this condition includes pelvic floor muscle training, biofeedback, electrical stimulation using a rectal electrode, transcutaneous electrical nerve stimulation, or a combination of methods. OBJECTIVES: To assess the effects of conservative management for urinary incontinence after transurethral, suprapubic, radical retropubic or perineal prostatectomy. SEARCH STRATEGY: The Cochrane Incontinence Group's trials register, Medline, Cinahl, Embase, PsycLit and ERIC all up to January 1999, and reference lists of relevant articles. We contacted investigators to locate studies and we handsearched the following conference proceedings: American Urological Association (1989-1999); Society of Urologic Nurses and Associates (1991-1998); Wound Ostomy and Continence Nurses (1996-1999); and International Continence Society (1980-1998). Date of most recent searches: January 1999. SELECTION CRITERIA: Randomised or quasi-randomised trials which evaluated conservative management aimed at improving urinary continence after prostatectomy. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the methodological quality of studies and abstracted data from included trials onto a standard form. MAIN RESULTS: Only five randomised trials were identified which included 365 men, each evaluating different treatments, and all studying men after radical prostatectomy. The trials were of moderate quality and data were not available for many of the pre-stated outcomes. Confidence intervals for both dichotomous and continuous data were wide; it was not possible to reliably identify or rule out a useful effect. Men's symptoms tended to improve over time, irrespective of management. REVIEWER'S CONCLUSIONS: The value of the various approaches to conservative management of post prostatectomy incontinence remains uncertain. Further well designed trials are needed.

Biofeedback, Psychology↗