A survey of experts to identify methods to detect problematic studies: Stage 1 of the INSPECT-SR Project.

Background: Randomised controlled trials (RCTs) inform healthcare decisions. Unfortunately, some published RCTs contain false data, and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs which have been conducted on a given topic. This means that any of these 'problematic studies' are likely to be included, but there are no agreed methods for identifying them. The INSPECT-SR project is developing a tool to identify problematic RCTs in systematic reviews of healthcare-related interventions. The tool will guide the user through a series of 'checks' to determine a study's authenticity. The first objective in the development process is to assemble a comprehensive list of checks to consider for inclusion. Methods: We assembled an initial list of checks for assessing the authenticity of research studies, with no restriction to RCTs, and categorised these into five domains: Inspecting results in the paper; Inspecting the research team; Inspecting conduct, governance, and transparency; Inspecting text and publication details; Inspecting the individual participant data. We implemented this list as an online survey, and invited people with expertise and experience of assessing potentially problematic studies to participate through professional networks and online forums. Participants were invited to provide feedback on the checks on the list, and were asked to describe any additional checks they knew of, which were not featured in the list. Results: Extensive feedback on an initial list of 102 checks was provided by 71 participants based in 16 countries across five continents. Fourteen new checks were proposed across the five domains, and suggestions were made to reword checks on the initial list. An updated list of checks was constructed, comprising 116 checks. Many participants expressed a lack of familiarity with statistical checks, and emphasized the importance of feasibility of the tool. Conclusions: A comprehensive list of trustworthiness checks has been produced. The checks will be evaluated to determine which should be included in the INSPECT-SR tool.

Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions.

INTRODUCTION: Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INveStigating ProblEmatic Clinical Trials in Systematic Reviews (INSPECT-SR) project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare-related interventions. METHODS AND ANALYSIS: The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: (1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, (2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, (3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in, (4) a consensus meeting to select checks to be included in a draft tool and to determine its format and (5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies and will help patients by protecting them from the influence of false data on their healthcare. ETHICS AND DISSEMINATION: The University of Manchester ethics decision tool was used, and this returned the result that ethical approval was not required for this project (30 September 2022), which incorporates secondary research and surveys of professionals about subjects relating to their expertise. Informed consent will be obtained from all survey participants. All results will be published as open-access articles. The final tool will be made freely available.

Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions.

Introduction: Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INSPECT-SR project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare related interventions. Methods and analysis: The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: 1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, 2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, 3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in 4) a consensus meeting to select checks to be included in a draft tool and to determine its format, 5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies, and will help patients by protecting them from the influence of false data on their healthcare.

Identifying and managing problematic trials: A research integrity assessment tool for randomized controlled trials in evidence synthesis.

Evidence synthesis findings depend on the assumption that the included studies follow good clinical practice and results are not fabricated or false. Studies which are problematic due to scientific misconduct, poor research practice, or honest error may distort evidence synthesis findings. Authors of evidence synthesis need transparent mechanisms to identify and manage problematic studies to avoid misleading findings. As evidence synthesis authors of the Cochrane COVID-19 review on ivermectin, we identified many problematic studies in terms of research integrity and regulatory compliance. Through iterative discussion, we developed a research integrity assessment (RIA) tool for randomized controlled trials for the update of this Cochrane review. In this paper, we explain the rationale and application of the RIA tool in this case study. RIA assesses six study criteria: study retraction, prospective trial registration, adequate ethics approval, author group, plausibility of methods (e.g., randomization), and plausibility of study results. RIA was used in the Cochrane review as part of the eligibility check during screening of potentially eligible studies. Problematic studies were excluded and studies with open questions were held in awaiting classification until clarified. RIA decisions were made independently by two authors and reported transparently. Using the RIA tool resulted in the exclusion of >40% of studies in the first update of the review. RIA is a complementary tool prior to assessing "Risk of Bias" aiming to establish the integrity and authenticity of studies. RIA provides a platform for urgent development of a standard approach to identifying and managing problematic studies.

Glucocorticoid with cyclophosphamide for paraquat-induced lung fibrosis.

BACKGROUND: Paraquat is an effective and widely used herbicide but is also a lethal poison. In many developing countries paraquat is widely available and inexpensive, making poisoning prevention difficult. However most of the people who become poisoned from paraquat have taken it as a means of suicide.Standard treatment for paraquat poisoning both prevents further absorption and reduces the load of paraquat in the blood through haemoperfusion or haemodialysis. The effectiveness of standard treatments is extremely limited.The immune system plays an important role in exacerbating paraquat-induced lung fibrosis. Immunosuppressive treatment using glucocorticoid and cyclophosphamide in combination is being developed and studied. OBJECTIVES: To assess the effects of glucocorticoid with cyclophosphamide on mortality in patients with paraquat-induced lung fibrosis. SEARCH METHODS: The most recent search was run on the 15th April 2014. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (Ovid), ISI WOS (SCI-EXPANDED, SSCI, CPCI-S & CPSI-SSH), trials registries, Chinese databases (, , ) and reference lists. SELECTION CRITERIA: RCTs were included in this review. All patients were to receive standard care, plus the intervention or control. The intervention was glucocorticoid with cyclophosphamide in combination versus a control of a placebo, standard care alone or any other therapy in addition to standard care. DATA COLLECTION AND ANALYSIS: The mortality risk ratio (RR) and 95% confidence interval (CI) was calculated for each study on an intention-to-treat basis. Data for all-cause mortality at final follow-up were summarised in a meta-analysis using a fixed-effect model. MAIN RESULTS: This systematic review includes three trials with a combined total of 164 participants who had moderate to severe paraquat poisoning. Patients who received glucocorticoid with cyclophosphamide in addition to standard care had a lower risk of death at final follow-up than those receiving standard care only (RR 0.72; 95% CI 0.59 to 0.89). AUTHORS' CONCLUSIONS: Based on the findings of three small RCTs of moderate to severely poisoned patients, glucocorticoid with cyclophosphamide in addition to standard care may be a beneficial treatment for patients with paraquat-induced lung fibrosis. To enable further study of the effects of glucocorticoid with cyclophosphamide for patients with moderate to severe paraquat poisoning, hospitals may provide this treatment as part of an RCT with allocation concealment.

Barbiturates for acute traumatic brain injury.

BACKGROUND: Raised intracranial pressure (ICP) is an important complication of severe brain injury, and is associated with high mortality. Barbiturates are believed to reduce ICP by suppressing cerebral metabolism, thus reducing cerebral metabolic demands and cerebral blood volume. However, barbiturates also reduce blood pressure and may, therefore, adversely effect cerebral perfusion pressure. OBJECTIVES: To assess the effects of barbiturates in reducing mortality, disability and raised ICP in people with acute traumatic brain injury. To quantify any side effects resulting from the use of barbiturates. SEARCH METHODS: The following electronic databases were searched on 26 September 2012: CENTRAL (The Cochrane Library), MEDLINE (Ovid SP), PubMed, EMBASE (Ovid SP), PsycINFO (Ovid SP), PsycEXTRA (Ovid SP), ISI Web of Science: Science Citation Index and Conference Proceedings Citation Index-Science. Searching was not restricted by date, language or publication status. We also searched the reference lists of the included trials and review articles. We contacted researchers for information on ongoing studies. SELECTION CRITERIA: Randomised controlled trials of one or more of the barbiturate class of drugs, where study participants had clinically diagnosed acute traumatic brain injury of any severity. DATA COLLECTION AND ANALYSIS: Two review authors screened the search results, extracted data and assessed the risk of bias in the trials. MAIN RESULTS: Data from seven trials involving 341 people are included in this review.For barbiturates versus no barbiturate, the pooled risk ratio (RR) of death from three trials was 1.09 (95% confidence interval (CI) 0.81 to 1.47). Death or disability, measured using the Glasgow Outcome Scale was assessed in two trials, the RR with barbiturates was 1.15 (95% CI 0.81 to 1.64). Two trials examined the effect of barbiturate therapy on ICP. In one, a smaller proportion of patients in the barbiturate group had uncontrolled ICP (68% versus 83%); the RR for uncontrolled ICP was 0.81 (95% CI 0.62 to 1.06). In the other, mean ICP was also lower in the barbiturate group. Barbiturate therapy results in an increased occurrence of hypotension (RR 1.80; 95% CI 1.19 to 2.70). For every four patients treated, one developed clinically significant hypotension. Mean body temperature was significantly lower in the barbiturate group.In one study of pentobarbital versus mannitol there was no difference in death between the two study groups (RR 1.21; 95% CI 0.75 to 1.94). Pentobarbital was less effective than mannitol for control of raised ICP (RR 1.75; 95% CI 1.05 to 2.92).In one study the RR of death with pentobarbital versus thiopental was 1.78 (95% CI 1.03 to 3.08) in favour of thiopental. Fewer people had uncontrollable ICP with thiopental (RR 1.64; 95% CI 1.03 to 2.60). There was no significant difference in the effects of pentobarbital versus thiopental for death or disability, measured using the Glasgow Outcome Scale (RR 1.31; 95% CI 0.88 to 1.94), or hypotension (RR 0.95; 95% CI 0.81 to 1.12). AUTHORS' 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 one in four patients. This hypotensive effect will offset any ICP lowering effect on cerebral perfusion pressure.

Glucocorticoid with cyclophosphamide for paraquat-induced lung fibrosis.

BACKGROUND: Paraquat is an effective and widely used herbicide but is also a lethal poison. In many developing countries paraquat is widely available and inexpensive, making poisoning prevention difficult. However most of the people who become poisoned from paraquat have taken it as a means of suicide.Standard treatment for paraquat poisoning both prevents further absorption and reduces the load of paraquat in the blood through haemoperfusion or haemodialysis. The effectiveness of standard treatments is extremely limited.The immune system plays an important role in exacerbating paraquat-induced lung fibrosis. Immunosuppressive treatment using glucocorticoid and cyclophosphamide in combination is being developed and studied. OBJECTIVES: To assess the effects of glucocorticoid with cyclophosphamide on mortality in patients with paraquat-induced lung fibrosis. SEARCH METHODS: To identify randomised controlled trials (RCTs) on this topic, we searched the Cochrane Injuries Group's Specialised Register (searched 1 February 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 1), MEDLINE (Ovid SP) (1946 January Week 3 2012), EMBASE (Ovid SP) (1947 to Week 4 2012), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to January 2012), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 to January 2012), Chinese Biomedical Literature and Retrieval System (CBM) (1978 to April 2012), Chinese Medical Current Contents (CMCC) (1995 to April 2012), and Chinese Medical Academic Conference (CMAC) (1994 to April 2012). Searches were completed on English language databases on 1 February 2012 and on Chinese language databases on 12 April 2012. SELECTION CRITERIA: RCTs were included in this review. All patients were to receive standard care, plus the intervention or control. The intervention was glucocorticoid with cyclophosphamide in combination versus a control of a placebo, standard care alone or any other therapy in addition to standard care. DATA COLLECTION AND ANALYSIS: The mortality risk ratio (RR) and 95% confidence interval (CI) was calculated for each study on an intention-to-treat basis. Data for all-cause mortality at final follow-up were summarised in a meta-analysis using a fixed-effect model. MAIN RESULTS: This systematic review includes three trials with a combined total of 164 participants who had moderate to severe paraquat poisoning. Patients who received glucocorticoid with cyclophosphamide in addition to standard care had a lower risk of death at final follow-up than those receiving standard care only (RR 0.72; 95% CI 0.59 to 0.89). AUTHORS' CONCLUSIONS: Based on the findings of three small RCTs of moderate to severely poisoned patients, glucocorticoid with cyclophosphamide in addition to standard care may be a beneficial treatment for patients with paraquat-induced lung fibrosis. To enable further study of the effects of glucocorticoid with cyclophosphamide for patients with moderate to severe paraquat poisoning, hospitals may provide this treatment as part of an RCT with allocation concealment.

Omega 3 fatty acid for the prevention of cognitive decline and dementia.

BACKGROUND: Evidence from observational studies suggests that diets high in omega-3 long-chain polyunsaturated fatty acids (PUFA) may protect people from cognitive decline and dementia. The strength of this potential protective effect has recently been tested in randomised controlled trials. OBJECTIVES: To assess the effects of omega-3 PUFA supplementation for the prevention of dementia and cognitive decline in cognitively healthy older people. SEARCH METHODS: We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on 6 April 2012 using the terms: "omega 3", PUFA, "fatty acids", "fatty acid", fish, linseed, eicosapentaenoic, docosahexaenoic. SELECTION CRITERIA: Randomised controlled trials of an omega-3 PUFA intervention which was provided for a minimum of six months to participants aged 60 years and over who were free from dementia or cognitive impairment at the beginning of the study. Two review authors independently assessed all trials. DATA COLLECTION AND ANALYSIS: The review authors sought and extracted data on incident dementia, cognitive function, safety and adherence, either from published reports or by contacting the investigators for original data. Data were extracted by two review authors. We calculated mean difference (MD) or standardised mean differences (SMD) and 95% confidence intervals (CI) on an intention-to-treat basis, and summarised narratively information on safety and adherence. MAIN RESULTS: Information on cognitive function at the start of a study was available on 4080 participants randomised in three trials. Cognitive function data were available on 3536 participants at final follow-up.In two studies participants received gel capsules containing either omega-3 PUFA (the intervention) or olive or sunflower oil (placebo) for six or 24 months. In one study, participants received margarine spread for 40 months; the margarine for the intervention group contained omega-3 PUFA. Two studies had cognitive health as their primary outcome; one study of cardiovascular disease included cognitive health as an additional outcome.None of the studies examined the effect of omega-3 PUFA on incident dementia. In two studies involving 3221 participants there was no difference between the omega-3 and placebo group in mini-mental state examination score at final follow-up (following 24 or 40 months of intervention); MD -0.07 (95% CI -0.25 to 0.10). In two studies involving 1043 participants, other tests of cognitive function such as word learning, digit span and verbal fluency showed no beneficial effect of omega-3 PUFA supplementation. Participants in both the intervention and control groups experienced either small or no cognitive declines during the studies.The main reported side-effect of omega-3 PUFA supplementation was mild gastrointestinal problems. Overall, minor adverse events were reported by fewer than 15% of participants, and reports were balanced between intervention groups. Adherence to the intervention was on average over 90% among people who completed the trials. All three studies included in this review are of high methodological quality. AUTHORS' CONCLUSIONS: Direct evidence on the effect of omega-3 PUFA on incident dementia is lacking. The available trials showed no benefit of omega-3 PUFA supplementation on cognitive function in cognitively healthy older people. Omega-3 PUFA supplementation is generally well tolerated with the most commonly reported side-effect being mild gastrointestinal problems.Further studies of longer duration are required. Longer-term studies may identify greater change in cognitive function in study participants which may enhance the ability to detect the possible effects of omega-3 PUFA supplementation in preventing cognitive decline in older people.

Omega 3 fatty acids and cognitive health in older people.

Oily fish and other sources of long-chain n-3 polyunsaturated fatty acids (n-3 LCPs) have been proposed as protective against dementia and age related cognitive impairment. The basic mechanisms underlying these proposed benefits have been postulated and experimental studies supporting the plausibility of the putative effects have been published. Observational epidemiological and case control studies also largely support a protective role of fish consumption on cognitive function with advancing age, albeit with important unexplained heterogeneity in findings. In this review we report the findings of the latest Cochrane review on the benefits of n-3 LCP supplementation on cognitive function among cognitively healthy older people and expand the review by including trials conducted with individuals with prevalent poor cognitive function or dementia. We identified seven relevant trials, four among cognitively healthy older people, and three among individuals with pre-existing cognitive decline or dementia, and overall conclude that there is no evidence to support the routine use of n-3 LCPs supplements for the prevention, or amelioration, of cognitive decline in later life. We identified several challenges in the design of intervention studies for the prevention of dementia and cognitive decline in older people that require careful consideration especially in recruitment and retention in long-term trials. Whether the lack of agreement in findings from mechanistic and observational data and from intervention studies reflects a real absence of benefit on cognitive function from n-3 LCP supplementation, or whether it reflects intrinsic limitations in the design of published studies remains open to question.

Omega 3 fatty acid for the prevention of cognitive decline and dementia

BACKGROUND: Evidence from observational studies suggests that diets high in omega-3 long-chain polyunsaturated fatty acids (PUFA) may protect people from cognitive decline and dementia. The strength of this potential protective effect has recently been tested in randomized controlled trials. OBJECTIVES: To assess the effects of omega-3 PUFA supplementation for the prevention of dementia and cognitive decline in cognitively healthy older people. METHODS: Search: We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on - 6 April 2012 using the terms: "omega 3", PUFA, "fatty acids", "fatty acid", fish, linseed, eicosapentaenoic, docosahexaenoic. Selection criteria: Randomised controlled trials of an omega-3 PUFA intervention which was provided for a minimum of six months to participants aged 60 years and over who were free from dementia or cognitive impairment at the beginning of the study. Two review authors independently assessed all trials. Data collection and analysis: The review authors sought and extracted data on incident dementia, cognitive function, safety and adherence, either from published reports or by contacting the investigators for original data. Data were extracted by two review authors. We calculated mean difference (MD) or standardised mean differences (SMD) and 95% confidence intervals (CI) on an intention-to-treat basis, and summarized narratively information on safety and adherence. MAIN RESULTS: Information on cognitive function at the start of a study was available on 4080 participants randomised in three trials. Cognitive function data were available on 3536 participants at final follow-up. In two studies participants received gel capsules containing either omega-3 PUFA (the intervention) or olive or sunflower oil (placebo) for six or 24 months. In one study, participants received margarine spread for 40 months; the margarine for the intervention group contained omega-3 PUFA. Two studies had cognitive health as their primary outcome; one study of cardiovascular disease included cognitive health as an additional outcome. None of the studies examined the effect of omega-3 PUFA on incident dementia. In two studies involving 3221 participants there was no difference between the omega-3 and placebo group in mini-mental state examination score at final follow-up (following 24 or 40 months of intervention); MD-0.07 (95% CI -0.25 to 0.10). In two studies involving 1043 participants, other tests of cognitive function such as word learning, digit span and verbal fluency showed no beneficial effect of omega-3 PUFA supplementation. Participants in both the intervention and control groups experienced either small or no cognitive declines during the studies. The main reported side-effect of omega-3 PUFA supplementation was mild gastrointestinal problems. Overall, minor adverse events were reported by fewer than 15% of participants, and reports were balanced between intervention groups. Adherence to the intervention was on average over 90% among people who completed the trials. All three studies included in this review are of high methodological quality. AUTHORS' CONCLUSIONS: Direct evidence on the effect of omega-3 PUFA on incident dementia is lacking. The available trials showed no benefit of omega-3 PUFA supplementation on cognitive function in cognitively healthy older people. Omega-3 PUFA supplementation is generally well tolerated with the most commonly reported side-effect being mild gastrointestinal problems. Further studies of longer duration are required. Longer-term studies may identify greater change in cognitive function in study participants which may enhance the ability to detect the possible effects of omega-3 PUFA supplementation in preventing cognitive decline in older people.

Glucocorticoid with cyclophosphamide for paraquat-induced lung fibrosis.

BACKGROUND: Paraquat is an effective and widely used herbicide but is also a lethal poison. In many developing countries paraquat is widely available and inexpensive, making poisoning prevention difficult. However most of the people who become poisoned from paraquat have taken it as a means of suicide.Standard treatment for paraquat poisoning both prevents further absorption and reduces the load of paraquat in the blood through haemoperfusion or haemodialysis. The effectiveness of standard treatments is extremely limited.The immune system plays an important role in exacerbating paraquat-induced lung fibrosis. Immunosuppressive treatment using glucocorticoid and cyclophosphamide in combination is being developed and studied. OBJECTIVES: To assess the effects of glucocorticoid with cyclophosphamide on mortality in patients with paraquat-induced lung fibrosis. SEARCH STRATEGY: To identify randomised controlled trials on this topic, we searched the Cochrane Injuries Group's Specialised Register (searched 15 Sept 2009), CENTRAL (The Cochrane Library 2009, Issue 3), MEDLINE (Ovid SP) (1950 September Week 1 2009), EMBASE (Ovid SP) (1980 to 2009 Week 37), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to Sept 2009), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 to Sept 2009), Chinese bio-medical literature & retrieval system (CBM) (1978 to Sept 2009), Chinese medical current contents (CMCC) (1995 to Sept 2009), and Chinese medical academic conference (CMAC) (1994-Sept 2009). The searches were completed in September 2009. SELECTION CRITERIA: Randomised controlled trials (RCTs) were included in this review. All patients were to receive standard care, plus the intervention or control. The intervention was glucocorticoid with cyclophosphamide in combination versus a control of a placebo, standard care alone, or any other therapy in addition to standard care. DATA COLLECTION AND ANALYSIS: The mortality risk ratio (RR) and 95% confidence interval (CI) was calculated for each study on an intention-to-treat basis. Data for all-cause mortality at final follow-up were summarised in a meta-analysis using a fixed-effects model. MAIN RESULTS: This systematic review includes three trials with a combined total of 164 participants who had moderate to severe paraquat poisoning. Patients who received glucocorticoid with cyclophosphamide in addition to standard care had a lower risk of death at final follow-up than those receiving standard care only (RR 0.72 (95% CI 0.59 to 0.89)). AUTHORS' CONCLUSIONS: Based on the findings of three small RCTs of moderate to severely poisoned patients, glucocorticoid with cyclophosphamide in addition to standard care may be a beneficial treatment for patients with paraquat-induced lung fibrosis. To enable further study of the effects of glucocorticoid with cyclophosphamide for patients with moderate to severe paraquat poisoning, hospitals may provide this treatment as part of an RCT with allocation concealment.

Hypothermia for traumatic head injury

It provides information on the treatment of traumatic head injury by using hypothermia.

Anti-fibrinolytic agents in post partum haemorrhage: a systematic review.

BACKGROUND: Post partum haemorrhage is a leading cause of maternal death worldwide. It also contributes to maternal morbidity as women may require a hysterectomy to control bleeding, or may require a blood transfusion, which can transmit viral infections. Anti-fibrinolytic agents have been proposed as a treatment for post partum haemorrhage. We conducted a systematic review to assess the effectiveness and safety of anti-fibrinolytic agents in post partum bleeding. METHODS: All randomised controlled trials of anti-fibrinolytic agents given for bleeding during the postpartum period were included in this review. We searched Medline, PubMed, EMBASE, Cochrane Central Register of Controlled trials, Web of Science, metaRegister of controlled trials, LILACS, Reproductive Health Library, African healthline, POPLINE, MedCarib, CINAHL, Clinicaltrials.gov and the reference lists of eligible trials. Two authors extracted data. Methodological quality was assessed by evaluating allocation concealment. The primary outcome was maternal mortality. Secondary outcomes were blood loss, blood transfusion, hysterectomy, mean haemoglobin concentration, thrombo-embolic events and other adverse effects. RESULTS: We identified three randomised controlled trials involving 461 participants. The trials compared tranexamic acid with no treatment and reported blood loss after delivery. In all three trials, allocation concealment was either inadequate or unclear. The administration of tranexamic acid was associated with a reduction in blood loss of 92 millilitres (95%CI 76 to 109). The most frequently reported adverse effect of tranexamic acid was nausea, although the increase was easily compatible with the play of chance (RR 4.63, 95%CI 0.23 to 95.14). CONCLUSION: Tranexamic acid may reduce blood loss in post partum haemorrhage. However, the quality of the currently available evidence is poor. Adequately powered, high quality randomised controlled trials are needed.

Hypothermia for traumatic head injury.

BACKGROUND: Hypothermia has been used in the treatment of head injury for many years. Encouraging results from small trials and laboratory studies led to renewed interest in the area and some larger trials. OBJECTIVES: To estimate the effect of mild hypothermia for traumatic head injury on mortality and long-term functional outcome complications. SEARCH STRATEGY: We searched the Injuries Group Specialised Register, Current Controlled Trials MetaRegister of trials, Zetoc, ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) and Conference Proceedings Citation Index-Science (CPCI-S), CENTRAL (The Cochrane Library), MEDLINE and EMBASE. We handsearched conference proceedings and checked reference lists of all relevant articles. The search was last updated in January 2009. SELECTION CRITERIA: Randomised controlled trials of hypothermia to a maximum of 35 degrees C for at least 12 consecutive hours versus control in patients with any closed traumatic head injury requiring hospitalisation. Two authors independently assessed all trials. DATA COLLECTION AND ANALYSIS: Data on death, Glasgow Outcome Scale and pneumonia were sought and extracted, either from published material or by contacting the investigators. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each trial on an intention-to-treat basis. MAIN RESULTS: We found 23 trials with a total of 1614 randomised patients. Twenty-one trials involving 1587 patients reported deaths. There were fewer deaths in patients treated with hypothermia than in the control group (OR 0.84, 95% CI 0.67 to 1.05). Nine trials with good allocation concealment showed no decrease in the likelihood of death compared with the control group, and this result was not statistically significant (OR 1.08, 95% CI 0.79 to 1.47). Twenty-one trials involving 1587 patients reported data on unfavourable outcomes (death, vegetative state or severe disability). Patients treated with hypothermia were less likely to have an unfavourable outcome than those in the control group (OR 0.76, 95% CI 0.61 to 0.93). Nine trials with good allocation concealment showed patients treated with hypothermia were less likely to have an unfavourable outcome than those in the control group, but the reduction was small and non-significant (OR 0.91, 95% CI 0.69 to 1.20). Hypothermia treatment was associated with a slight increase in the odds of pneumonia (OR 1.31, 95% CI 0.93 to 1.86) but there was a reduction in pneumonia for trials with good allocation concealment (4 trials analysed separately, 294 patients, OR 0.79, 95% CI 0.49 to 1.27) although in both cases the results are not statistically significant. AUTHORS' CONCLUSIONS: There is no evidence that hypothermia is beneficial in the treatment of head injury. Hypothermia may be effective in reducing death and unfavourable outcomes for traumatic head injured patients, but significant benefit was only found in low quality trials. Low quality trials have a tendency to overestimate the treatment effect. The high quality trials found no decrease in the likelihood of death with hypothermia, but this finding was not statistically significant and could be due to the play of chance. Hypothermia should not be used except in the context of a high quality randomised controlled trial with good allocation concealment.

Hypothermia for traumatic head injury.

BACKGROUND: Hypothermia has been used in the treatment of head injury for many years. Encouraging results from small trials and laboratory studies led to renewed interest in the area and some larger trials. OBJECTIVES: To estimate the effect of mild hypothermia for traumatic head injury on mortality and long-term functional outcome complications. SEARCH STRATEGY: We searched the Injuries Group Specialised Register, Current Controlled Trials MetaRegister of trials, Zetoc, Web of Knowledge; Science Citation Index [expanded], CENTRAL, MEDLINE and EMBASE. We handsearched conference proceedings and checked reference lists of relevant articles. The search was updated on 23 May 2008. SELECTION CRITERIA: Randomised controlled trials of hypothermia to a maximum of 35 degrees C for at least 12 hours versus control in patients with any closed traumatic head injury requiring hospitalisation. Two authors independently assessed all trials. DATA COLLECTION AND ANALYSIS: Data on death, Glasgow Outcome Scale and pneumonia were sought and extracted, either from published material or by contacting the investigators. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each trial on an intention-to-treat basis. MAIN RESULTS: We found 22 trials with a total of 1409 randomised patients. Twenty trials involving 1382 patients reported deaths. There were fewer deaths in patients treated with hypothermia than in the control group (OR 0.76, 95% CI 0.60 to 0.97). Eight trials with good allocation concealment showed a non-significant reduction in the likelihood of death for patients treated with hypothermia (OR 0.96, 95% CI 0.68 to 1.35). Twenty trials involving 1382 patients reported data on unfavourable outcomes (death, vegetative state or severe disability). Patients treated with hypothermia were less likely to have an unfavourable outcome than those in the control group (OR 0.69, 95% CI 0.55 to 0.86). Eight trials with good allocation concealment showed a non-significant reduction in the likelihood of unfavourable outcome for patients treated with hypothermia (OR 0.79, 95% CI 0.57 to 1.08). Hypothermia treatment was associated with an increase in odds of pneumonia but this increase was not statistically significant for trials with good allocation concealment (3 trials, 69 patients, OR 1.06, 95% CI 0.38 to 2.97). AUTHORS' CONCLUSIONS: Hypothermia may be effective in reducing death and unfavourable outcomes for traumatic head injured patients, but significant benefit was only found in low quality trials. Low quality trials have a tendency to overestimate the treatment effect. The high quality trials found some statistically non-significant benefit of hypothermia which could be due to the play of chance. Hypothermia may increase the risk of pneumonia. Due to uncertainties in its effects, hypothermia should only be given to patients taking part in a randomised controlled trial with good allocation concealment.