Association of a P2RX7 gene missense variant with brachycephalic dog breeds.

Missense variants are associated with various phenotypic traits and disorders in dogs. The canine P2RX7 gene, coding the ATP-gated P2X7 receptor ion channel, contains four known missense variants. The current study aimed to examine the presence of these variants in a random sample of pedigree and mixed-pedigree dogs. Exons 3, 8, 11 and 13 of the P2RX7 gene, encoding these four respective variants, in 65 dogs were assessed by Sanger sequencing and combined with existing sequencing data from another 69 dogs. The distribution of these variants was then evaluated in all 134 dogs combined and separately within individual breeds including 35 different pure breeds. The rs23314713 (p.Phe103Leu) and rs23315462 (p.Pro452Ser) variants were present in 47 and 40% of all dogs studied respectively, with the rs23314713 variant associated with brachycephalic breeds. Among pedigree dogs, the rs23314713 and rs23315462 variants were associated with brachycephalic and non-brachycephalic breeds respectively. The rs851148233 (p.Arg270Cys) and rs850760787 (p.Arg365Gln) variants were present only in dogs of Cocker Spaniel and Labrador Retriever pedigrees respectively. No other missense variants were found in exons 3, 8, 11 and 13 of the P2RX7 gene within the dogs. In conclusion, the rs23314713 and rs23315462 missense variants of the P2RX7 gene are present in a large proportion of dogs, with the rs23314713 variant associated with a number of brachycephalic breeds. However, the association of this variant with dogs of bulldog ancestry, not brachycephaly per se, cannot be excluded.

The mystery of our mathematical universe.

Why is it that fundamental laws discovered through pure mathematics have been able to describe the behavior of our physical world with such precision? Given that the physical universe is composed of mathematical properties, some have posited that mathematics is the language of the universe, whose laws reveal what appears to be a hidden order in the natural world. Physicist S. James Gates, Jr. and science writer Margaret Wertheim explore the uncanny ability of mathematics to reveal the laws of nature.

Correlation between neonatal outcomes of twins depends on the outcome: secondary analysis of twelve randomised controlled trials.

OBJECTIVE: To estimate the magnitude of the correlation between neonatal outcomes of twins and demonstrate how this information can be used in the design of randomised controlled trials (RCTs) in women with twin pregnancies. DESIGN: Secondary analysis of data from 12 RCTs. SETTING: Obstetric care in multiple countries, 2004-2012. POPULATION OR SAMPLE: 4504 twin pairs born to women who participated in RCTs to assess treatments given during pregnancy. METHODS: Intraclass correlation coefficients (ICCs) were estimated using log-binomial and linear models. MAIN OUTCOME MEASURES: Perinatal death, respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular haemorrhage, necrotising enterocolitis, sepsis, neonatal intensive care unit admission, birthweight, low birthweight and two composite measures of adverse neonatal outcome. RESULTS: ICCs for the composite measures of adverse neonatal outcome were all above 0.5, indicating moderate to strong correlation between adverse outcomes of twins. For individual neonatal outcomes, median ICCs across trials ranged from 0.13 to 0.79 depending on the outcome. An example illustrates how ICCs can be used in sample size calculations for RCTs in women with twin pregnancies. CONCLUSIONS: The correlation between neonatal outcomes of twins varies considerably between outcomes and may be lower than expected. Our ICC estimates can be used for designing and analysing RCTs that recruit women with twin pregnancies and for performing meta-analyses that include such RCTs. Researchers are encouraged to report ICCs for neonatal outcomes in twins in their own RCTs. TWEETABLE ABSTRACT: Correlation between neonatal outcomes of twins depends on the outcome and may be lower than expected.

A call for more science in forensic science.

Forensic science is critical to the administration of justice. The discipline of forensic science is remarkably complex and includes methodologies ranging from DNA analysis to chemical composition to pattern recognition. Many forensic practices developed under the auspices of law enforcement and were vetted primarily by the legal system rather than being subjected to scientific scrutiny and empirical testing. Beginning in the 1990s, exonerations based on DNA-related methods revealed problems with some forensic disciplines, leading to calls for major reforms. This process generated a National Academy of Science report in 2009 that was highly critical of many forensic practices and eventually led to the establishment of the National Commission for Forensic Science (NCFS) in 2013. The NCFS was a deliberative body that catalyzed communication between nonforensic scientists, forensic scientists, and other stakeholders in the legal community. In 2017, despite continuing problems with forensic science, the Department of Justice terminated the NCFS. Just when forensic science needs the most support, it is getting the least. We urge the larger scientific community to come to the aid of our forensic colleagues by advocating for urgently needed research, testing, and financial support.

Post-admission outcomes of participants in the PARAMEDIC trial: A cluster randomised trial of mechanical or manual chest compressions.

BACKGROUND: The PARAMEDIC cluster randomised trial evaluated the LUCAS mechanical chest compression device, and did not find evidence that use of mechanical chest compression led to an improvement in survival at 30 days. This paper reports patient outcomes from admission to hospital to 12 months after randomisation. METHODS: Information about hospital length of stay and intensive care management was obtained through linkage with Hospital Episode Statistics and the Intensive Care National Audit and Research Centre. Patients surviving to hospital discharge were approached to complete questionnaires (SF-12v2, EQ-5D, MMSE, HADS and PTSD-CL) at 90days and 12 months. The study is registered with Current Controlled Trials, number ISRCTN08233942. RESULTS: 377 patients in the LUCAS arm and 658 patients in the manual chest compression were admitted to hospital. Hospital and intensive care length of stay were similar. Long term follow-up assessments were limited by poor response rates (53.7% at 3 months and 55.6% at 12 months). Follow-up rates were lower in those with worse neurological function. Among respondents, long term health related quality of life outcomes and emotional well-being was similar between groups. Cognitive function, measured by MMSE, was marginally lower in the LUCAS arm mean 26.9 (SD 3.7) compared to control mean 28.0 (SD 2.3), adjusted mean difference -1.5 (95% CI -2.6 to -0.4). CONCLUSION: There were no clinically important differences identified in outcomes at long term follow-up between those allocated to the mechanical chest compression compared to those receiving manual chest compression.

Characteristics of patients who are not resuscitated in out of hospital cardiac arrests and opportunities to improve community response to cardiac arrest.

AIM: This study explores why resuscitation is withheld when emergency medical staff arrive at the scene of a cardiac arrest and identifies modifiable factors associated with this decision. METHODS: This is a secondary analysis of unselected patients who sustained an out of hospital cardiac arrest attended by ambulance vehicles participating in a randomized controlled trial of a mechanical chest compression device (PARAMEDIC trial). Patients were categorized as 'non-resuscitation' patients if there was a do-not-attempt-cardiopulmonary-resuscitation (DNACPR) order, signs unequivocally associated with death or resuscitation was deemed futile (15min had elapsed since collapse with no bystander-CPR and asystole recorded on EMS arrival). RESULTS: Emergency Medical Services attended 11,451 cardiac arrests. Resuscitation was attempted or continued by Emergency Medical Service staff in 4805 (42%) of cases. Resuscitation was withheld in 6646 cases (58%). 711 (6.2%) had a do not attempt resuscitation decision, 4439 (38.8%) had signs unequivocally associated with death and in 1496 cases (13.1%) CPR was considered futile. Those where resuscitation was withheld due to futility were characterised by low bystander CPR rates (7.2%) and by being female. CONCLUSIONS: Resuscitation was withheld by ambulance staff in over one in ten (13.1%) victims of out of hospital cardiac arrest on the basis of futility. These cases were associated with a very low rate of bystander CPR. Future studies should explore strengthening the 'Chain of Survival' to increase the community bystander CPR response and evaluate the effect on the numbers of survivors from out of hospital cardiac arrest.

Beta-Agonist Lung injury TrIal-2 (BALTI-2): a multicentre, randomised, double-blind, placebo-controlled trial and economic evaluation of intravenous infusion of salbutamol versus placebo in patients with acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a major cause of mortality in intensive care patients and lacks effective treatments. A previous randomised controlled Phase II trial suggested that an intravenous (i.v.) infusion of salbutamol may be beneficial, as it reduced extravascular lung water and plateau airway pressure. The Beta-Agonist Lung injury TrIal-2 (BALTI-2) was initiated to evaluate the effects of this intervention on mortality in patients with ARDS. OBJECTIVES: To evaluate whether or not, in patients with ARDS, an i.v. infusion of salbutamol given at 15 µg/kg ideal body weight (IBW)/hour for up to 7 days, compared with a placebo (0.9% sodium chloride) infusion, reduces 28-day all-cause mortality and other clinical outcomes. To evaluate salbutamol's clinical effectiveness and its cost-effectiveness in subgroups of patients. DESIGN: A multicentre, randomised, placebo-controlled trial. SETTING: Forty-six intensive care units (ICUs) in the UK. PARTICIPANTS: Patients were eligible if they (1) were intubated and mechanically ventilated patients in participating ICUs; (2) were within 72 hours of onset of ARDS; (3) fulfilled American-European Consensus Conference definition for ARDS {acute-onset, severe hypoxaemic respiratory failure [partial pressure of oxygen in arterial blood/fraction of inspired oxygen ≤ 26.7 kPa (200 mmHg)] and bilateral infiltrates on the chest radiograph in the absence of clinical evidence of left atrial hypertension}; and (4) were aged ≥ 16 years. INTERVENTIONS: Intravenous infusion of salbutamol (15 µg/kg IBW/hour) or placebo (0.9% saline) for up to 7 days. MAIN OUTCOME MEASURES: All-cause mortality 28 days after randomisation, mortality at (first) discharge from ICU, mortality at (first) discharge from hospital, number of ventilator-free days, number of organ failure-free days, mortality at 12 months post randomisation, side effects (tachycardia/new arrhythmia/lactic acidosis) sufficient to stop treatment with trial drug, health-related quality of life (European Quality of Life-5 Dimensions and Short Form questionnaire-12 items at 6 and 12 months after randomisation), length of stay in critical care unit and length of stay in hospital. RESULTS: Forty-six ICUs recruited patients to the trial. A total of 326 patients were randomised; 162 were allocated to salbutamol and 164 to placebo. One patient in each group withdrew consent. Recruitment was stopped after the second interim analysis because of safety concerns. Salbutamol increased 28-day mortality: 55 (34%) of 161 patients died in the salbutamol group compared with 38 (23%) of 163 in the placebo group (risk ratio 1.47, 95% confidence interval 1.03 to 2.08). CONCLUSIONS: Treatment with i.v. salbutamol early in the course of ARDS was poorly tolerated, is unlikely to be beneficial and could worsen outcomes. Further trials of ß-agonists in patients with ARDS are unlikely to be conducted. Some questions remain, such as whether or not there may be benefit at a different dose or in specific populations, but any studies investigating these would require a very strong rationale. TRIAL REGISTRATION: Current Controlled Trials ISRCTN38366450. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Managing Injuries of the Neck Trial (MINT): a randomised controlled trial of treatments for whiplash injuries.

OBJECTIVES: To examine the clinical effectiveness of a stepped care approach over a 12-month period after an acute whiplash injury; to estimate the costs and cost-effectiveness of each strategy including treatments and subsequent health-care costs; and to gain participants' perspective on experiencing whiplash injury, NHS treatment, and recovery within the context of the Managing Injuries of the Neck Trial (MINT). DESIGN: Two linked, pragmatic, randomised controlled trials. In Step 1, emergency departments (EDs) were cluster randomised to usual care advice (UCA) or The Whiplash Book advice (WBA)/active management advice. In Step 2, participants were individually randomised to either a single session of advice from a physiotherapist or a physiotherapy package of up to six sessions. An economic evaluation and qualitative study were run in parallel with the trial. SETTING: Twelve NHS trusts in England comprising 15 EDs. PARTICIPANTS: People who attended EDs with an acute whiplash injury of whiplash-associated disorder grades I-III were eligible for Step 1. People who had attended EDs with whiplash injuries and had persistent symptoms 3 weeks after ED attendance were eligible for Step 2. INTERVENTIONS: In Step 1, the control intervention was UCA and the experimental intervention was a psycho-educational intervention (WBA/active management advice). In Step 2 the control treatment was reinforcement of the advice provided in Step 1 and the experimental intervention was a package of up to six physiotherapy treatments. MAIN OUTCOME: The primary outcome was the Neck Disability Index (NDI), which measures severity and frequency of pain and symptoms, and a range of activities including self-care, driving, reading, sleeping and recreation. Secondary outcomes included the mental and physical health-related quality-of-life (HRQoL) subscales of the Short Form questionnaire-12 items (SF-12) and the number of work days lost. RESULTS: A total of 3851 patients were recruited to Step 1 of the trial. 1598 patients attending EDs were randomised to UCA, and 2253 were randomised to WBA/active management. Outcome data were obtained at 12 months for 70% and 80% of participants at Step 1 and Step 2, respectively. The majority of people recovered from the injury. Eighteen per cent of the Step 1 cohort had late whiplash syndrome. There was no statistically or clinically significant difference observed in any of the outcomes for participants attending EDs randomised to UCA or active management advice [difference in NDI 0.5, 95% confidence interval (CI) -1.8 to 2.8]. In Step 2 the physiotherapy package resulted in improvements in neck disability at 4 months compared with a single advice session, but these effects were small at the population level (difference in NDI -3.2, 95% CI -5.8 to -0.7). The physiotherapy package was accompanied by a significant reduction in the number of work days lost at 4-month follow-up (difference -40.2, 95% CI -44.3 to -35.8). CONCLUSIONS: MINT suggests that enhanced psycho-educational interventions in EDs are no more effective than UCA in reducing the burden of acute whiplash injuries. A physiotherapy package provided to people who have persisting symptoms within the first 6 weeks of injury produced additional short-term benefits in neck disability compared with a single physiotherapy advice session. However, from a health-care perspective, the physiotherapy package was not cost-effective at current levels of willingness to pay. Both experimental treatments were associated with increased cost with no discernible gain in health-related quality of life. However, an important benefit of the physiotherapy package was a reduction in work days lost; consequently, the intervention may prove cost-effective at the societal level. TRIAL REGISTRATION: Current Controlled Trials ISRCTN33302125. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 49. See the HTA programme website for further project information.

Extension of Bacillus endospore gas dynamic heating studies to multiple species and test conditions.

AIMS: Shock wave-induced damage to a variety of Bacillus endospore species is studied for a wide range of postshock temperatures and test times in oxidative and non-oxidative gas environments. METHODS AND RESULTS: Bacillus atrophaeus and Bacillus subtilis endospores are nebulized into an aqueous aerosol, loaded into the Stanford aerosol shock tube (SAST) and subjected to shock waves of controlled strength. Endospores experience uniform test temperatures between 500 and 1000 K and pressures ranging from 2 to 7 atm, for either a short test time (∼2·5 ms) or a relatively long test time (∼45 ms). During this process, the bioaerosol is observed using in situ laser absorption and scattering diagnostics. Additionally, shock-treated samples are extracted for ex situ analysis including viability plating and flow cytometry. For short test times, results are consistent with previous studies; all endospore species begin to lose the ability to form colonies when shock-heated to temperatures above 500 K, while significant breakdown in morphology is observed for postshock temperatures above 700 K. Oxidative bath gases did not affect viability losses or morphological breakdown rates. Experiments with extended postshock test time showed increased viability loss with minimal morphological damage for shocks between 600 and 700 K. CONCLUSIONS: Genetic differences between B. subtilis and B. atrophaeus endospores do not confer noticeable gains in resistance to shock heating. Oxidative environments do not exacerbate shock-induced damage to endospores. Extended test time experiments reinforce our hypothesis that a temperature/time-dependent inactivation mechanism that does not involve morphological breakdown exists at low-to-moderate postshock temperatures. SIGNIFICANCE AND IMPACT OF THE STUDY: The methodology and experiments described in this paper extend the study of the interactions of endospores with shock/blast waves to new species and environmental conditions.

Bacillus endospore resistance to gas dynamic heating.

AIM: To develop a novel laboratory procedure for the study of shock wave-induced damage to Bacillus endospores. METHODS AND RESULTS: Bacillus atrophaeus endospores are nebulized into an aerosol, loaded into the stanford aerosol shock tube and subjected to shock waves of controlled strength. Endospores experience uniform test temperatures between 500 and 1000K and pressures ranging from 2 to 7atm, for a relatively short time (2-3ms). During this process, the bioaerosol is observed using in situ laser absorption and scattering diagnostics. Additionally, shock-treated samples are extracted for ex situ analysis including viability plating, flow cytometry and SEM imaging. Measurements indicate that endospores lose the ability to form colonies when heated to test temperatures above 500K while significant breakdown in morphology is observed at test temperatures above 750K. CONCLUSION: These results demonstrate the disruption of essential biochemical pathways or biomolecules prior to the onset of significant endospore morphological deterioration. SIGNIFICANCE AND IMPACT OF THE STUDY: This novel laboratory approach to study the interaction of endospores with shock waves provides an experimental means to investigate the mechanisms of endospore resistance to rapid heating. In addition, this methodology allows for the direct simulation of a blast wave-bioaerosol interaction in an atmospheric environment.

A national survey of clinical practice for the management of whiplash-associated disorders in UK emergency departments.

OBJECTIVE: To undertake a national survey to determine current practice for the management of whiplash injuries in UK emergency departments (ED). METHODS: Postal questionnaire survey. 316 lead consultants from all UK ED with annual new attendances of over 50 000 people were asked to indicate the use of a range of treatments and the frequency with which these treatments were used. Samples of written advice were requested and content analysis was conducted and compared with survey responses. RESULTS: The response rate was 79% (251/316). The intervention most frequently used was verbal advice to exercise, reported by 84% of respondents for most or all cases, and advice against the use of a collar (83%). Other treatments reported as being used frequently were written advice and anti-inflammatory medication. 106 consultants (42%) provided a sample of written materials. Reference to expected recovery and encouragement for early return to activities were included in less than 6%. Nearly 50% of written materials contained information on how to use a soft collar and 61% contained information on solicitors and pursuing a personal injury claim. There were important differences between reported verbal behaviours and written advice. CONCLUSION: Verbal advice is the primary method for managing whiplash injuries in ED and is usually supplemented by written advice. Within individual hospitals there is a lack of consistency between verbal and written advice. The promotion of personal injury claims is a common feature of written advice. Research is required to develop effective and consistent models of advice.

Interventions for twin-twin transfusion syndrome: a Cochrane review.

We performed a Cochrane review to assess which of the treatments for twin-twin transfusion syndrome (TTTS) improves fetal, childhood and maternal outcomes. This article represents a version of the review which includes additional data to the published version. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (April 2007) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, October 2007) for randomized and quasi-randomized studies of amnioreduction, laser coagulation and septostomy and compared their outcomes. We also searched conference proceedings and contacted the authors of published trials for clarification and additional data. No trials compared intervention with no intervention. Three studies (253 women) were included. Laser coagulation resulted in less overall death (48% vs. 59%; relative risk (RR), 0.81; 95% CI, 0.65-1.01 adjusted for clustering; two trials, 364 fetuses), perinatal death (26% vs. 44%; RR, 0.59; 95% CI, 0.40-0.87 adjusted for clustering; one trial, 284 fetuses) and neonatal death (8% vs. 26%; RR, 0.29; 95% CI, 0.14-0.61 adjusted for clustering; one trial, 284 fetuses) when compared with amnioreduction. There was no difference in perinatal outcome between amnioreduction and septostomy. More babies were alive without neurological abnormality at the age of 6 months in the laser group than in the amnioreduction group (52% vs. 31%; RR, 1.66; 95% CI, 1.17-2.35 adjusted for clustering; one trial). There was no difference in the proportion of babies alive at 6 months that had undergone treatment for major neurological abnormality between the laser coagulation and the amnioreduction groups (4% vs. 7%; RR, 0.58; 95% CI, 0.18-1.86 adjusted for clustering; one trial). The results suggest that endoscopic laser coagulation of anastomotic vessels should be considered in the treatment of all stages of TTTS to improve perinatal and neonatal outcome.

Interventions for the treatment of twin-twin transfusion syndrome.

BACKGROUND: Twin-twin transfusion syndrome, a condition affecting monochorionic twin pregnancies, is associated with a high risk of perinatal mortality and morbidity. A number of treatments have been introduced to treat the condition but it is unclear which intervention improves maternal and fetal outcome. OBJECTIVES: The objective of this review was to evaluate the impact of treatment modalities in twin-twin transfusion syndrome. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (October 2007) and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2007, Issue 4). We also searched conference proceedings and made personal contact with experts active in the area of the review. SELECTION CRITERIA: Randomised and quasi-randomised studies of amnioreduction versus laser coagulation, septostomy versus laser coagulation or septostomy versus amnioreduction. DATA COLLECTION AND ANALYSIS: One review author assessed eligibility and extracted data, which were checked by a second author. We contacted study authors for additional information. MAIN RESULTS: Two studies (213 women) were included. This review shows that laser coagulation of anastomotic vessels results in less death of both infants per pregnancy (relative risk (RR) 0.33; 95% confidence interval (CI) 0.16 to 0.67, one trial), less perinatal death (RR 0.59; 95% CI 0.0.40 to 0.87 adjusted for cluster, one trial) and less neonatal death (RR 0.29; 95% CI 0.14 to 0.61 adjusted for cluster, one trial) than in pregnancies treated with amnioreduction. There is no difference in perinatal outcome between amnioreduction and septostomy. A third study is awaiting assessment. More babies were alive without neurological abnormality at the age of six months in the laser group than the amnioreduction groups (RR 1.66; 95% CI 1.17 to 2.35 adjusted for clustering, one trial). This difference did not persist beyond six months of age. There was no significant difference in the babies alive at six months with neurological abnormality treated by laser coagulation or amnioreduction (RR 0.58; 95% CI 0.18 to 1.86 adjusted for clustering, one trial). AUTHORS' CONCLUSIONS: Endoscopic laser coagulation of anastomotic vessels should be considered in the treatment of all stages of twin-twin transfusion syndrome to improve perinatal outcome. Further research on the effect of treatment on milder forms of twin-twin transfusion syndrome (Quintero stage 1 and 2) are required. The long-term outcomes of survivors from the studies included in this review are required.

Multifactorial assessment and targeted intervention for preventing falls and injuries among older people in community and emergency care settings: systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of multifactorial assessment and intervention programmes to prevent falls and injuries among older adults recruited to trials in primary care, community, or emergency care settings. DESIGN: Systematic review of randomised and quasi-randomised controlled trials, and meta-analysis. DATA SOURCES: Six electronic databases (Medline, Embase, CENTRAL, CINAHL, PsycINFO, Social Science Citation Index) to 22 March 2007, reference lists of included studies, and previous reviews. REVIEW METHODS: Eligible studies were randomised or quasi-randomised trials that evaluated interventions to prevent falls that were based in emergency departments, primary care, or the community that assessed multiple risk factors for falling and provided or arranged for treatments to address these risk factors. DATA EXTRACTION: Outcomes were number of fallers, fall related injuries, fall rate, death, admission to hospital, contacts with health services, move to institutional care, physical activity, and quality of life. Methodological quality assessment included allocation concealment, blinding, losses and exclusions, intention to treat analysis, and reliability of outcome measurement. RESULTS: 19 studies, of variable methodological quality, were included. The combined risk ratio for the number of fallers during follow-up among 18 trials was 0.91 (95% confidence interval 0.82 to 1.02) and for fall related injuries (eight trials) was 0.90 (0.68 to 1.20). No differences were found in admissions to hospital, emergency department attendance, death, or move to institutional care. Subgroup analyses found no evidence of different effects between interventions in different locations, populations selected for high risk of falls or unselected, and multidisciplinary teams including a doctor, but interventions that actively provide treatments may be more effective than those that provide only knowledge and referral. CONCLUSIONS: Evidence that multifactorial fall prevention programmes in primary care, community, or emergency care settings are effective in reducing the number of fallers or fall related injuries is limited. Data were insufficient to assess fall and injury rates.

Continuous support for women during childbirth.

BACKGROUND: Historically, women have been attended and supported by other women during labour. However, in recent decades in hospitals worldwide, continuous support during labour has become the exception rather than the routine. Concerns about the consequent dehumanization of women's birth experiences have led to calls for a return to continuous support by women for women during labour. OBJECTIVES: Primary: to assess the effects, on mothers and their babies, of continuous, one-to-one intrapartum support compared with usual care. Secondary: to determine whether the effects of continuous support are influenced by: (1) routine practices and policies in the birth environment that may affect a woman's autonomy, freedom of movement and ability to cope with labour; (2) whether the caregiver is a member of the staff of the institution; and (3) whether the continuous support begins early or later in labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (February 2007). SELECTION CRITERIA: All published and unpublished randomized controlled trials comparing continuous support during labour with usual care. DATA COLLECTION AND ANALYSIS: We used standard methods of the Cochrane Collaboration Pregnancy and Childbirth Group. All authors participated in evaluation of methodological quality. One author and a research assistant independently extracted the data. We sought additional information from the trial authors. We used relative risk for categorical data and weighted mean difference for continuous data to present the results. MAIN RESULTS: Sixteen trials involving 13,391 women met inclusion criteria and provided usable outcome data. Primary comparison: women who had continuous intrapartum support were likely to have a slightly shorter labour, were more likely to have a spontaneous vaginal birth and less likely to have intrapartum analgesia or to report dissatisfaction with their childbirth experiences. Subgroup analyses: in general, continuous intrapartum support was associated with greater benefits when the provider was not a member of the hospital staff, when it began early in labour and in settings in which epidural analgesia was not routinely available. AUTHORS' CONCLUSIONS: All women should have support throughout labour and birth.

Interventions for prevention of drug use by young people delivered in non-school settings.

BACKGROUND: Interventions intended to prevent or reduce use of drugs by young people may be delivered in schools or in other settings. This review aims to summarise the current literature about the effectiveness of interventions delivered in non schools settings. OBJECTIVES: (1) - To summarise the current evidence about the effectiveness of interventions delivered in non-school settings intended to prevent or reduce drug use by young people under 25;(2) - To investigate whether interventions' effects are modified by the type and setting of the intervention, and the age of young people targeted;(3) - To identify areas where more research is needed. SEARCH STRATEGY: We searched Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library Issue 4, 2004), MEDLINE (1966-2004), EMBASE (1980-2004), PsycInfo (1972-2004), SIGLE (1980-2004), CINAHL (1982-2004) and ASSIA (1987-2004). We searched also reference lists of review articles and retrieved studies. SELECTION CRITERIA: Randomised trials that evaluated an intervention targeting drug use by young people under 25 years of age, delivered in a non-school setting, compared with no intervention or another intervention, that reported substantive outcomes relevant to the review. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. Results were tabulated, as studies were considered too dissimilar to combine using meta-analysis. MAIN RESULTS: Seventeen studies, 9 cluster randomised studies, with 253 clusters, 8 individually randomised studies with 1230 participants, evaluating four types of intervention: motivational interviewing or brief intervention, education or skills training, family interventions and multi-component community interventions. Many studies had methodological drawbacks, especially high levels of loss to follow-up. There were too few studies for firm conclusions. One study of motivational interviewing suggested that this intervention was beneficial on cannabis use. Three family interventions (Focus on Families, Iowa Strengthening Families Program and Preparing for the Drug-Free Years), each evaluated in only one study, suggested that they may be beneficial in preventing cannabis use. The studies of multi component community interventions did not find any strong effects on drug use outcomes, and the two studies of education and skills training did not find any differences between the intervention and control groups. AUTHORS' CONCLUSIONS: There is a lack of evidence of effectiveness of the included interventions. Motivational interviewing and some family interventions may have some benefit. Cost-effectiveness has not yet been addressed in any studies, and further research is needed to determine whether any of these interventions can be recommended.