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PubMed2005

A new strategy to screen molecular imaging probe uptake in cell culture without radiolabeling using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

UNLABELLED: Numerous new molecular targets for diseases are rapidly being identified and validated in the postgenomic era, urging scientists to explore novel techniques for accelerating molecular probe development. In this study, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was investigated as a potential tool for high-throughput screening and characterization of molecular imaging probes. Specifically, MALDI-TOF-MS was used to screen a small library of phosphonium cations for their ability to accumulate in cells. METHODS: C6 cells incubated with phosphonium cations at room temperature were collected and lysed for experiments. Calibration curves for the internal standard, methyltriphenyl phosphonium, and for tetraphenylphosphonium bromide (TPP) and other phosphonium cations were first established. The time course of TPP uptake by C6 cells was then quantified using both MALDI-TOF-MS and liquid scintillation counting with (3)H-TPP. In addition, MALDI-TOF-MS was used to screen a library of 8 phosphonium cations and subsequently rank their ability to penetrate membranes and accumulate in cells. Finally, the accumulation of 4-fluorophenyltriphenyl phosphonium (FTPP) in the membrane potential-modulated cells was also measured by MALDI-TOF-MS. RESULTS: MALDI-TOF-MS spectra clearly revealed that TPP was easily identified from cell lysates even as early as 10 min after incubation and that levels as low as 0.11 fmol of TPP per cell could be detected, suggesting the high sensitivity of this technique. The time course of TPP influx determined by both MALDI-TOF-MS and radioactivity counting showed no statistically significant difference (P > 0.05 for all time points). These data validated MALDI-TOF-MS as an alternative approach for accurately measuring uptake of phosphonium cations by cells. TPP and FTPP demonstrated greater accumulation in cells than did the other cations evaluated in this study. Furthermore, uptake profiles suggested that FTPP preserves the membrane potential-dependent uptake property of TPP in cell cultures. Taken together, these data justify further synthesis and evaluation of (18)F-FTPP as a molecular probe for imaging mitochondrial dysfunction. CONCLUSION: These results demonstrate that MALDI-TOF-MS is a powerful analytic tool for rapid screening and characterization of phosphonium cations as molecular probes. This technique can potentially be applied to the evaluation of other imaging probes or drugs and thus may facilitate their rational design and development.

Animals↗
PubMed2000

Antibiotics for preterm premature rupture of membranes.

OBJECTIVES: The aim of the review was to evaluate the effectiveness and the immediate and long-term safety of the effects of administering antibiotics to women with preterm prelabour rupture of membranes on maternal infectious morbidity, fetal and neonatal morbidity and mortality, and longer term childhood development. SEARCH STRATEGY: All randomized trials identified using the search strategy described by the Cochrane Pregnancy and Childbirth Group. SELECTION CRITERIA: All trials which reported clinically relevant outcomes (as opposed to laboratory data) were included. DATA COLLECTION AND ANALYSIS: Data were extracted from each report without any blinding of either the results or the treatments which women received. Unpublished data were sought from a number of authors. MAIN RESULTS: Antibiotic treatment following pPROM is effective at prolonging pregnancy and reducing maternal and neonatal infectious morbidity. There is no statisically proven benefit that their use improves neonatal mortality and morbidity in the short or long term. REVIEWER'S CONCLUSIONS: There are insufficient data to recommend routine prescription of antibiotics in this clinical situation. Research into this area should continue.

Anti-Bacterial Agents↗
PubMed2006

A collaborative hit-to-lead investigation leveraging medicinal chemistry expertise with high throughput library design, synthesis and purification capabilities.

High throughput screening (HTS) campaigns, where laboratory automation is used to expose biological targets to large numbers of materials from corporate compound collections, have become commonplace within the lead generation phase of pharmaceutical discovery. Advances in genomics and related fields have afforded a wealth of targets such that screening facilities at larger organizations routinely execute over 100 hit-finding campaigns per year. Often, 10(5) or 10(6) molecules will be tested within a campaign/cycle to locate a large number of actives requiring follow-up investigation. Due to resource constraints at every organization, traditional chemistry methods for validating hits and developing structure activity relationships (SAR) become untenable when challenged with hundreds of hits in multiple chemical families per target. To compound the issue, comparison and prioritization of hits versus multiple screens, or physical chemical property criteria, is made more complex by the informatics issues associated with handling large data sets. This article describes a collaborative research project designed to simultaneously leverage the medicinal chemistry and drug development expertise of the Novartis Institutes for Biomedical Research Inc. (NIBRI) and ArQule Inc.'s high throughput library design, synthesis and purification capabilities. The work processes developed by the team to efficiently design, prepare, purify, assess and prioritize multiple chemical classes that were identified during high throughput screening, cheminformatics and molecular modeling activities will be detailed.

Chemistry, Pharmaceutical↗
PubMed2004

Discharge planning from hospital to home.

BACKGROUND: Discharge planning is a routine feature of health systems in many countries. The aim is to reduce hospital length of stay and unplanned readmission to hospital, and improve the co ordination of services following discharge from hospital thereby bridging the gap between hospital and place of discharge. Sometimes discharge planning is offered as part of an integrated package of care, which may cover both the hospital and community. The focus of this review is discharge planning that occurs while a patient is in hospital; we exclude studies that evaluate discharge planning with follow up care. OBJECTIVES: To determine the effectiveness of planning the discharge of patients moving from hospital. SEARCH STRATEGY: Relevant studies were identified using Medline, Embase, SIGLE database for grey literature, Bioethics database, Health Plan, Psych. Lit, Sociofile, CINAHL, Cochrane Library, Econ Lit, Social Science Citation Index, EPOC register. The review was updated using the EPOC trials register in August 2002. SELECTION CRITERIA STUDY DESIGN: randomised controlled trials (RCTs) that compare discharge planning (the development of an individualised discharge plan) with routine discharge care. PARTICIPANTS: all patients in hospital. INTERVENTION: the development of an individualised discharge plan. DATA COLLECTION AND ANALYSIS: Data analysis and quality assessment was undertaken independently by two reviewers using a data checklist. Studies are grouped according to patient group (elderly medical patients, surgical patients, and those with a mix of conditions), and by outcome. MAIN RESULTS: Three new studies were included in this update. In total we included eleven RCTS: 6 trials recruited patients with a medical condition (2,368 patients), and four recruited patients with a mix of medical and surgical conditions (2,983 patients), one of these four recruited medical and surgical patients as separate groups, and the final trial recruited 97 patients in a psychiatric hospital and from a general hospital. We failed to detect a difference between groups in mortality for elderly patients with a medical condition (OR 1.44 95% CI 0.82 to 2.51), hospital length of stay (weighted mean difference -0.86, 95% CI -1.9 to 0.18), readmission rates (OR 0.91 95% CI 0.67 to 1.23) and being discharged from hospital to home (OR 1.15 95% CI 0.72 to 1.82). This was also the case for trials recruiting patients recovering from surgery and those recruiting patients with a mix of medical and surgical conditions. One trial comparing a structured care pathway for patients recovering from a stroke with multidisciplinary care reported a significant rate of improvement in functional ability and quality of life for the control group (median change in Barthel score between 4 to 12 weeks of 2 points for the treatment group, versus 6 for the control group, p<0.01); (Euroqol scores at 6 months 63 for the treatment group, vs. 72 for the control group, p<0.005). Two trials reported that patients with medical conditions allocated to discharge planning reported increased satisfaction compared with those who received routine discharge. No statistically significant differences were reported for overall health care costs. REVIEWER'S CONCLUSIONS: The impact of discharge planning on readmission rates, hospital length of stay, health outcomes and cost is uncertain. This reflects a lack of power as the degree to which we could pool data was restricted by the different reported measures of outcome. It is possible that even a small reduction in length of stay, or readmission rate, could have an impact on the timeliness of subsequent admissions in a system where there is an shortage of acute hospital beds.

Controlled Clinical Trials as Topic↗
PubMed2000

Topical umbilical cord care at birth.

BACKGROUND: Umbilical cord infection caused many neonatal deaths before aseptic techniques were used. OBJECTIVES: The objective of this review was to assess the effects of topical cord care in preventing cord infection, illness and death. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register (Cochrane Library issue 4, 1997) and Medline. We also contacted experts in the field. SELECTION CRITERIA: Randomised and quasi-randomised trials of topical cord care compared with no routine care, and comparisons between different forms of care. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trial quality and extracted data. MAIN RESULTS: Ten studies were included, all from developed countries. No systemic infections or deaths were observed in any of the studies reviewed. Cord and other skin infections within six weeks of observation were not affected by use of antiseptics. There was a trend to reduced colonization with antibiotics compared to antiseptics and no treatment. Antiseptics prolonged the time to cord separation. Use of antiseptics was associated with a reduction in maternal concern about the cord. REVIEWER'S CONCLUSIONS: Simply keeping the cord clean appears to be as effective and safe as using antibiotics or antiseptics.

Anti-Bacterial Agents↗
PubMed2002

Development of the pancreas in medaka.

In the present work, pancreatic organogenesis has been studied in the medaka (Oryzias latipes), a teleost fish with several advantages as an experimental system in developmental biology. We demonstrated that the pancreas develops from three primordia budding from the dorsal and ventral faces of the gut epithelium. Such buds then fuse to form a single endocrine islet surrounded by exocrine tissue. Interestingly, the endocrine tissue forms only from the dorsal bud. We next analyzed a collection of medakas that had been hybridized with cDNAs derived from an anterior brain library. We found new clones expressed in the pancreatic region demonstrating that the medaka can be used to define new genes expressed in the pancreatic region that follow a specific spatial and temporal pattern of expression.

Animals↗
PubMed2000

The Ensemble/Legacy Chimera extension: standardized user and programmer interface to molecular Ensemble data and Legacy modeling programs.

Ensemble/Legacy is a toolkit extension of the Object Technology Framework (OTF) that exposes an object oriented interface for accessing and manipulating ensembles (collections of molecular conformations that share a common chemical topology) and driving Legacy programs (such as MSMS, AMBER, X-PLOR, CORMA/MARDIGRAS, Dials and Windows, and CURVES). Ensemble/Legacy provides a natural programming interface for running Legacy programs on ensembles of molecules and accessing the resulting data. Using the OTF reduces the time cost of developing a new library to store and manipulate molecular data and also allows Ensemble/Legacy to integrate into the Chimera visualization program. The extension to Chimera exposes the Legacy functionality using a graphical user interface that greatly simplifies the process of modeling and analyzing conformational ensembles. Furthermore, all the C++ functionality of the Ensemble/Legacy toolkit is "wrapped" for use in the Python programming language. More detailed documentation on using Ensemble/Legacy is available online (http:¿picasso.nmr.ucsf.edu/dek/ensemble. html).

Computer Graphics↗
PubMed2002

The Australian Twin Registry.

The Australian Twin Registry (ATR), established in the late 1970s, is a volunteer registry of over 30,000 pairs of Australian twins of all zygosity types and ages unselected for their health or medical history. The ATR does not undertake research itself but acts as facilitator, providing an important national and international resource for medical and scientific researchers across a broad range of disciplines. Its core functions are the maintenance of an up-to-date database containing basic contact details and baseline information, and the management of access to the resource in ways that enhance research capacity within Australia while protecting the rights of twins. The ATR has facilitated more than 200 studies using a variety of designs, including classic biometrical twin and twin family studies, co-twin control studies, intervention studies, longitudinal studies, and studies of issues relevant specifically to twins. These have yielded more than 300 peer-reviewed publications to date. Areas of major research include studies of behavior, musculoskeletal conditions, teeth and face patterns, cardiovascular risk factors, substance abuse, and risk factors for melanoma and breast cancer. Extensive longitudinal data are available for around 10,000 pairs. DNA samples have been obtained from more than 6000 twins. Considerable efforts are devoted to maintaining the commitment of registry members and recruitment. The ATR hopes to secure funding to expand its activities, including the systematic collection of DNA samples, so that it can continue to play a major role in the development of twin research and contribute to the annotation of the human genome.

Adolescent↗
PubMedDate not supplied

Does a multidisciplinary total parenteral nutrition team improve patient outcomes? A systematic review.

BACKGROUND: Total parenteral nutrition (TPN) is a specialized form of nutrition support. The complexity associated with the management of patients receiving TPN therapy has led to the development of multidisciplinary TPN teams. The purpose of this review was to critically analyze the literature and present the best available evidence that investigated the effectiveness of multidisciplinary TPN teams in the provision of TPN to adult hospitalized patients. METHODS: A systematic review of studies identified from the Cochrane Library (2001, Issue 4), CINAHL, Complete MEDLINE, Complete Biomedical Collection, Complete Nursing Collection, and EMBASE, published in any language. RESULTS: Eleven studies, 4 with concurrent controls and 7 with historical controls, were eligible for inclusion in the review. Results of the studies indicate that the incidence of total mechanical complications is reduced in patients managed by the TPN team. However, the benefit of the TPN team in the reduction of catheter-related sepsis remains inconclusive. Four of the 5 studies reported fewer total metabolic and electrolyte abnormalities in patients cared for by the team, and these patients were more likely to receive their optimal caloric intake. However it was unclear if the management of the patients by the TPN team prevented the inappropriate use of TPN therapy. Although only 2 studies (n = 356) investigated total costs associated with management of patients by the TPN teams, there was evidence that a team approach is a cost-effective strategy. CONCLUSIONS: Overall, the general effectiveness of the TPN team has not been conclusively demonstrated. There is evidence that patients managed by TPN teams have a reduced incidence of total mechanical complications; however, it is unclear if there is a reduction in catheter-related sepsis and metabolic and electrolyte complications. The available evidence, although limited, suggests financial benefits from the introduction of multidisciplinary TPN teams in the hospital setting.

Cost-Benefit Analysis↗
PubMed2005

Calorie and protein-enriched formula versus standard term formula for improving growth and development in preterm or low birth weight infants following hospital discharge.

BACKGROUND: Preterm and low birth weight infants are often growth-restricted at hospital discharge. Feeding infants post-hospital discharge with calorie and protein-enriched formula milk might facilitate "catch-up" growth and improve development. OBJECTIVES: To review the evidence from randomised controlled trials that feeding following hospital discharge with calorie and protein-enriched formula compared with standard term formula improves growth and development for preterm or low birth weight infants. SEARCH STRATEGY: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2004), MEDLINE (1966 - December 2004), EMBASE (1980 - December 2004), CINAHL (1982 - December 2004), conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared the effect of feeding preterm or low birth weight infants post-hospital discharge with calorie and protein-enriched formula compared with standard term formula. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two authors, and synthesis of data using weighted mean difference and a fixed effects model for meta-analysis. MAIN RESULTS: We found six trials that were eligible for inclusion. These recruited a total of 424 infants and were generally of good methodological quality. These trials found little evidence that feeding with calorie and protein-enriched formula milk affected growth and development. Because of differences in the way individual trials measured and presented outcomes, data synthesis was limited. Meta-analysis of data from two trials found a statistically significant effect on crown-heel length at 18 months post-term (weighted mean difference 9.7 millimetres (95% confidence interval 3.2 to 16.2)), but not on weight or head circumference. Meta-analysis of data from the two trials that assessed neurodevelopment at 18 months post-term did not reveal a statistically significant difference in either Bayley Mental Development Index (weighted mean difference 0.23 (95% confidence interval -2.99 to 3.45)) or Psychomotor Development Index (weighted mean difference 0.56 (95% confidence interval -1.95 to 3.07)). There are not yet any data on growth or development through later childhood. AUTHORS' CONCLUSIONS: The limited available data do not provide strong evidence that feeding preterm or low birth weight infants following hospital discharge with calorie and protein-enriched formula compared with standard term formula affects growth rates or development up to 18 months post-term.

Child Development↗
PubMed2006

An efficient rapid system for profiling the cellular activities of molecular libraries.

Rapid quantitative methods for characterizing small molecules, peptides, proteins, or RNAs in a broad array of cellular assays would allow one to discover new biological activities associated with these molecules and also provide a more comprehensive profile of drug candidates early in the drug development process. Here we describe a robotic system, termed the automated compound profiler, capable of both propagating a large number of cell lines in parallel and assaying large collections of molecules simultaneously against a matrix of cellular assays in a highly reproducible manner. To illustrate its utility, we have characterized a set of 1,400 kinase inhibitors in a panel of 35 activated tyrosine-kinase-dependent cellular assays in dose-response format in a single experiment. Analysis of the resulting multidimensional dataset revealed subclusters of both inhibitors and kinases with closely correlated activities. The approach also identified activities for the p38 inhibitor BIRB796 and the dual src/abl inhibitor BMS-354825 and exposed the expected side activities for Glivec/STI571, including cellular inhibition of c-kit and platelet-derived growth factor receptor. This methodology provides a powerful tool for unraveling the cellular biology and molecular pharmacology of both naturally occurring and synthetic chemical diversity.

Animals↗
PubMed2000

Creating a human phantom for the virtual human program.

A high-resolution human phantom--a computer representation of the human anatomy--is needed as part of the Virtual Human (VH) simulation environment being developed by Oak Ridge National Laboratory and collaborators. Within the VH environment, this 3D anatomical phantom is coupled with physiological models and data to investigate a wide range of human biological and physical responses to stimuli. This paper describes how the phantom was created using the Visible Human (male) image data from the U.S. National Library of Medicine. Initially, X-ray computed tomography (CT) as well as photographic images of the Visible Human (male) torso were segmented and classified with software developed using IDL. From these data, non-uniform, rational B-spline (NURBS) spatial models were fitted to represent the surfaces of discrete body structures such as bones and organs. This collection of NURBS models, referred to as the NURBS VH, defines the fundamental Virtual Human phantom. The NURBS VH is compatible with modeling and animation software, enabling dynamic manipulation of body structures and their associated visual representations. The organization of the structural data lends itself to existing and evolving Web and electronic communication standards, making it attractive for applications such as medical training. In addition, finite-element (FE) meshes were created from the NURBS VH for use in trauma simulation, electromagnetic field exposure modeling, dosimetry, and other applications requiring spatially-defined tissue properties. The ability to scale the NURBS VH to account for age and size and the ability to easily animate NURBS objects yield a very flexible human phantom for the VH simulation environment.

Anatomy, Cross-Sectional↗
PubMed2000

Kangaroo mother care to reduce morbidity and mortality in low birthweight infants.

BACKGROUND: Kangaroo mother care (KMC), defined as skin-to-skin contact between a mother and her newborn, frequent and exclusive or nearly exclusive breastfeeding, and early discharge from hospital, has been proposed as an alternative to conventional neonatal care for low birthweight (LBW) infants. OBJECTIVES: To determine whether there is evidence to support the use of KMC in LBW infants as an alternative to conventional care after the initial period of stabilization with conventional care. SEARCH STRATEGY: We used the standard search strategy of the Neonatal Review Group of the Cochrane Collaboration. MEDLINE, EMBASE, LILACS, POPLINE and CINAHL databases, and the Cochrane Controlled Trials Register (Cochrane Library) up to Issue 2, 2000, were searched using the key words terms "kangaroo mother care" or "kangaroo mother method" or "skin-to-skin contact" and "infants" or "low birthweight infants". SELECTION CRITERIA: Randomised trials comparing KMC and conventional neonatal care in LBW infants. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. Statistical analysis was conducted using the standard Cochrane Collaboration methods. MAIN RESULTS: Three studies, involving 1362 infants, were included. All the trials were conducted in developing countries. The studies were of moderate to poor methodological quality. The most common shortcomings were in the areas of blinding procedures for those who collected the outcomes measures, handling of drop outs, and completeness of follow-up. The great majority of results consist of results of a single trial. KMC was associated with the following reduced risks: nosocomial infection at 41 weeks' corrected gestational age (relative risk 0.49, 95% confidence interval 0.25 to 0.93), severe illness (relative risk 0.30, 95% confidence interval 0.14 to 0.67), lower respiratory tract disease at 6 months follow-up (relative risk 0.37, 95% confidence interval 0.15 to 0.89), not exclusively breastfeeding at discharge (relative risk 0.41, 95% confidence interval 0.25 to 0.68), and maternal dissatisfaction with method of care (relative risk 0.41, 95% confidence interval 0.22 to 0.75). KMC infants had gained more weight per day by discharge (weighted mean difference 3.6 g/day, 95% confidence interval 0.8 to 6.4). Scores on mother's sense of competence according to infant stay in hospital and admission to NICU were better in KMC than in control group (weighted mean differences 0.31 [95% confidence interval 0.13 to 0.50] and 0.28 [95% confidence interval 0.11 to 0.46], respectively). Scores on mother's perception of social support according to infant stay in NICU were worse in KMC group than in control group (weighted mean difference -0.18 (95% confidence interval -0.35 to -0.01). There was no evidence of a difference in infant mortality. However, serious concerns about the methodological quality of the included trials weaken credibility in these findings. REVIEWER'S CONCLUSIONS: Although KMC appears to reduce severe infant morbidity without any serious deleterious effect reported, there is still insufficient evidence to recommend its routine use in LBW infants. Well designed randomized controlled trials of this intervention are needed.

Breast Feeding↗
PubMed2006

1,3,5-Triazepane-2,6-diones as structurally diverse and conformationally constrained dipeptide mimetics: identification of malaria liver stage inhibitors from a small pilot library.

The development of the 1,3,5-triazepane-2,6-dione system as a novel, conformationally restricted, and readily accessible class of dipeptidomimetics is reported. The synthesis of the densely functionalized 1,3,5-triazepane-2,6-dione skeleton was achieved in only four steps from a variety of simple linear dipeptide precursors. To extend the practical value of 1,3,5-triazepane-2,6-diones, a general polymer-assisted solution-phase synthesis approach amenable to library production in a multiparallel format was developed. The conformational preferences of the 1,3,5-triazepane-2,6-dione skeleton were investigated in detail by NMR spectroscopy and X-ray diffraction. The ring exhibits a characteristic folded conformation which was compared to that of related dipeptide-derived scaffolds including the more planar 2,5-diketopiperazine (DKP). Molecular and structural diversity was increased further through post-cyclization appending operations at urea nitrogens. Preliminary biological screens of a small collection of 1,3,5-triazepane-2,6-diones revealed inhibitors of the underexplored malaria liver stage and suggest strong potential for this dipeptide-derived scaffold to interfere with and to modulate biological pathways.

Combinatorial Chemistry Techniques↗
PubMed2000

Barbiturates for acute traumatic brain injury.

BACKGROUND: Raised intracranial pressure (ICP) is an important complication of severe brain injury, and is associated with a high mortality rate. Barbiturates are believed to reduce intracranial pressure by suppressing cerebral metabolism, thus reducing cerebral metabolic demands and cerebral blood volume. However, barbiturates also reduce blood pressure and therefore may adversely effect cerebral perfusion pressure. OBJECTIVES: To assess the effects of barbiturates in reducing raised intracranial pressure, mortality and morbidity in people with acute traumatic brain injury. To quantify any side effects resulting from the use of barbiturates. SEARCH STRATEGY: The review draws largely on the search strategy developed for the Cochrane Injuries Group as a whole. However, in addition the Cochrane Library was searched in December 1996 using the text terms "barbiturate*," "pentobarb*," "phenobarb*," "head," and "brain." An updated search was done in April 1999. SELECTION CRITERIA: Randomised or quasi randomised trials of any one or more of the barbiturate class of drugs (amobarbital, barbital, hexobarbital, mephobarbital, methohexital, murexide, pentobarbital, phenobarbital, secobarbital, thiobarbiturate) where study participants had a clinically diagnosed acute traumatic brain injury of any severity. DATA COLLECTION AND ANALYSIS: The reviewer extracted the data and assessed the quality of allocation concealment in the trials. MAIN RESULTS: The pooled relative risk for death (barbiturate vs no barbiturate) was 1.09 (95%CI 0.81 to 1.47). The pooled effect of barbiturates on adverse neurological outcome, measured using the Glasgow Outcome Scale (death, persistent vegetative state or severe disability) was 1.15 (95% 0.81 to 1.64). Two studies examined the effect of barbiturate therapy on intracranial pressure. In the study by Eisenberger et al, a smaller proportion of patients in the barbiturate group had uncontrolled ICP (68% vs 83%). The relative risk for uncontrolled ICP was 0.81 (95%CI 0.62 to 1.06). Similarly, in the study by Ward et al, mean ICP was lower in the barbiturate treated group. Barbiturate therapy results in an increase in the occurrence of hypotension (RR=1.80 95%CI 1.19 to 2.70). For every four patients treated one will develop clinically significant hypotension. Mean body temperature was significantly lower in the barbiturate treated group. Schwartz et al compared pentobarbital with mannitol in the control of intracranial pressure. Pentobarbital was less effective than mannitol for control of raised ICP. 68% of patients in the pentobarbital treated group required a second drug for the treatment of raised intracranial pressure compared to 39% in the mannitol treated group (RR=1.75 95%CI 1.05 to 2.92). There was no substantial difference in mortality between the two study groups (RR=1.18 95%CI 0.73 to 1.92). REVIEWER'S CONCLUSIONS: There is no evidence that barbiturate therapy in patients with acute severe head injury improves outcome. Barbiturate therapy results in a fall in blood pressure in 1 in 4 treated patients. The hypotensive effect of barbiturate therapy will offset any ICP lowering effect on cerebral perfusion pressure.

Barbiturates↗
PubMed2004

Nasal versus oral route for placing feeding tubes in preterm or low birth weight infants.

BACKGROUND: Enteral feeding tubes for preterm or low birth weight infants may be placed via either the nose or mouth. Nasal placement may compromise respiration. However, orally placed tubes may be more prone to displacement, local irritation, and vagal stimulation. OBJECTIVES: To assess the available evidence from randomised controlled trials concerning the effects of nasally placed compared with orally placed feeding tubes on growth and development, and the incidence of adverse consequences in preterm or low birth weight infants. SEARCH STRATEGY: We used the standard search strategy of the Cochrane Neonatal Review Group, including electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2004), MEDLINE (1966 - April 2004), EMBASE (1988 - April 2004), and CINAHL (1982- April 2004), conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared the use of the nasal versus oral route for placing feeding tubes in preterm or low birth weight infants. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author, and analysis of data using relative risk, risk difference and mean difference. MAIN RESULTS: We found only one eligible trial. Forty-two infants participated in the study. This primary aim of the trial was to assess the effect of oral versus nasal placement of feeding tubes on the incidence of apnea and periodic breathing in preterm infants. The trial did not report data on the pre-specified primary outcomes for this review (growth and development). REVIEWERS' CONCLUSIONS: There are insufficient data available to inform practice. A large randomised controlled trial is required to determine if the use of nasally placed feeding tubes compared with orally placed feeding tubes improves growth and development, without increasing adverse consequences in preterm or low birth weight infants.

Enteral Nutrition↗
PubMed2004

Acupuncture for induction of labour.

BACKGROUND: This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. The use of complementary therapies is increasing and some women look to complementary therapies during pregnancy and childbirth to be used alongside conventional medical practice. Acupuncture involves the insertion of very fine needles into specific points of the body. The limited observational studies to date suggest acupuncture for induction of labour appears safe, has no known teratogenic effects, and may be effective. The evidence regarding the clinical effectiveness of this technique is limited. OBJECTIVES: To determine the effects of acupuncture for third trimester cervical ripening or induction of labour. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register (February 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2003), PubMed (1966 to present), CISCOM (1960 to present), EMBASE (1980 to present) and bibliographies of relevant papers. SELECTION CRITERIA: Clinical trials comparing acupuncture used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods. DATA COLLECTION AND ANALYSIS: A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. MAIN RESULTS: One trial of 56 women was included in the review. Data were not in a form that could be included in the meta-analysis. REVIEWER'S CONCLUSIONS: There is a need for well-designed randomised controlled trials to evaluate the role of acupuncture to induce labour and for trials to assess clinically meaningful outcomes.

Acupuncture Therapy↗
PubMed2005

Interventions to improve outpatient referrals from primary care to secondary care.

BACKGROUND: The primary care specialist interface is a key organisational feature of many health care systems. Patients are referred to specialist care when investigation or therapeutic options are exhausted in primary care and more specialised care is needed. Referral has considerable implications for patients, the health care system and health care costs. There is considerable evidence that the referral processes can be improved. OBJECTIVES: To estimate the effectiveness and efficiency of interventions to change outpatient referral rates or improve outpatient referral appropriateness. SEARCH STRATEGY: We conducted electronic searches of the Cochrane Effective Practice and Organisation of Care (EPOC) group specialised register (developed through extensive searches of MEDLINE, EMBASE, Healthstar and the Cochrane Library) (February 2002) and the National Research Register. SELECTION CRITERIA: Randomised controlled trials, controlled clinical trials, controlled before and after studies and interrupted time series of interventions to change or improve outpatient referrals. Participants were primary care physicians. The outcomes were objectively measured provider performance or health outcomes. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Seventeen studies involving 23 separate comparisons were included. Nine studies (14 comparisons) evaluated professional educational interventions. Ineffective strategies included: passive dissemination of local referral guidelines (two studies), feedback of referral rates (one study) and discussion with an independent medical adviser (one study). Generally effective strategies included dissemination of guidelines with structured referral sheets (four out of five studies) and involvement of consultants in educational activities (two out of three studies). Three studies evaluated organisational interventions (patient management by family physicians compared to general internists, attachment of a physiotherapist to general practices and requiring a second 'in-house' opinion prior to referral), all of which were effective. Five studies (six comparisons) evaluated financial interventions. Two studies evaluating change from a capitation based to mixed capitation and fee-for-service system and from a fee-for-service to a capitation based system (with an element of risk sharing for secondary care services) observed a reduction in referral rates. Modest reductions in referral rates of uncertain significance were observed following the introduction of the general practice fundholding scheme in the United Kingdom (UK). One study evaluating the effect of providing access to private specialists demonstrated an increase in the proportion of patients referred to specialist services but no overall effect on referral rates. AUTHORS' CONCLUSIONS: There are a limited number of rigorous evaluations to base policy on. Active local educational interventions involving secondary care specialists and structured referral sheets are the only interventions shown to impact on referral rates based on current evidence. The effects of 'in-house' second opinion and other intermediate primary care based alternatives to outpatient referral appear promising.

Family Practice↗