Glucocorticoid with cyclophosphamide for oral paraquat poisoning.

BACKGROUND: This an update of a Cochrane Review. Paraquat is a widely used herbicide, but is also a lethal poison. In some low- and middle-income countries (LMICs) paraquat is commonly available and inexpensive, making poisoning prevention difficult. Most of the people poisoned by paraquat have taken it as a means of self-poisoning. Standard treatment for paraquat poisoning 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 has been developed and studied as an intervention for paraquat poisoning. OBJECTIVES: To assess the effects of glucocorticoid with cyclophosphamide for moderate to severe oral paraquat poisoning. SEARCH METHODS: The most recent searches were run in September 2020. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Injuries Trials Register), Ovid MEDLINE(R), Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid OLDMEDLINE, Embase Classic + Embase (Ovid), ISI WOS (SCI-EXPANDED, SSCI, CPCI-S, and CPSI-SSH), and trials registries. We also searched the following three resources: China National Knowledge Infrastructure database (CNKI ); Wanfang Data (); and VIP () on 12 November 2020. We examined the reference lists of included studies and review papers. SELECTION CRITERIA: We included randomised controlled trials (RCTs). For this update, in accordance with Cochrane Injuries' Group policy (2015), we included only prospectively registered RCTs for trials published after 2010. We included trials which assessed the effects of glucocorticoid with cyclophosphamide delivered in combination. Eligible comparators were standard care (with or without a placebo), or any other therapy in addition to standard care. Outcomes of interest included mortality and infections. DATA COLLECTION AND ANALYSIS: We calculated the mortality risk ratio (RR) and 95% confidence interval (CI). Where possible, we summarised data for all-cause mortality at relevant time periods (from hospital discharge to three months after discharge) in meta-analysis, using a fixed-effect model. We conducted sensitivity analyses based on factors including whether participants were assessed at baseline for plasma paraquat levels. We also reported data on infections within one week after initiation of treatment. MAIN RESULTS: We included four trials with a total of 463 participants. The included studies were conducted in Taiwan (Republic of China), Iran, and Sri Lanka. Most participants were male. The mean age of participants was 28 years. We judged two of the four included studies, including the largest and most recently conducted study (n = 299), to be at low risk of bias for key domains including sequence generation. We assessed one study to be at high risk of selection bias and another at unclear risk, since allocation concealment was either not mentioned in the trial report or explicitly not undertaken. We assessed three of the four studies to be at unclear risk of selective reporting, as no protocols could be identified. An important source of heterogeneity amongst the included studies was the method of assessment of participants' baseline severity using analysis of plasma levels (two studies employed this method, whilst the other two did not). No studies assessed the outcome of mortality at 30 days following ingestion of paraquat. Low-certainty evidence from two studies indicates that glucocorticoids with cyclophosphamide in addition to standard care may slightly reduce the risk of death in hospital compared to standard care alone ((RR 0.82, 95% CI 0.68 to 0.99; participants = 322); results come from sensitivity analysis excluding studies not assessing plasma at baseline). However, we have limited confidence in this finding as heterogeneity was high (I2 = 77%) and studies varied in terms of size and comparators. A single large study provided data showing that there may be little or no effect of treatment at three months post discharge from hospital (RR 0.98, 95% CI 0.85 to 1.13; 1 study, 293 participants; low-certainty evidence); however, analysis of long-term results amongst participants whose injuries arose from self-poisoning must be interpreted with caution. We remain uncertain of the effect of glucocorticoids with cyclophosphamide on infection within one week after initiation of the treatment; this outcome was assessed by two small studies only (31 participants, very low-certainty evidence) that considered leukopenia as a proxy or risk factor for infection. Neither study reported infections in any participants. AUTHORS' CONCLUSIONS: Low-certainly evidence suggests that glucocorticoids with cyclophosphamide in addition to standard care may slightly reduce mortality in hospitalised people with oral paraquat poisoning. However, we have limited confidence in this finding because of substantial heterogeneity and concerns about imprecision. Glucocorticoids with cyclophosphamide in addition to standard care may have little or no effect on mortality at three months after hospital discharge. We are uncertain whether glucocorticoid with cyclophosphamide puts patients at an increased risk of infection due to the limited evidence available for this outcome. Future research should be prospectively registered and CONSORT-compliant. Investigators should attempt to ensure an adequate sample size, screen participants for inclusion rigorously, and seek long-term follow-up of participants. Investigators may wish to research the effects of glucocorticoid in combination with other treatments.

Intraoperative mild hypothermia for postoperative neurological deficits in people with intracranial aneurysm.

BACKGROUND: Rupture of an intracranial aneurysm causes aneurysmal subarachnoid haemorrhage, which is one of the most devastating clinical conditions. It can be classified into five Grades using the Hunt-Hess or World Federation of Neurological Surgeons (WFNS) scale. Grades 4 and 5 predict poor prognosis and are known as 'poor grade', while grade 1, 2, and 3 are known as 'good grade'. Disturbances of intracranial homeostasis and brain metabolism are known to play certain roles in the sequelae. Hypothermia has a long history of being used to reduce metabolic rate, thereby protecting organs where metabolism is disturbed, and may potentially cause harm. OBJECTIVES: To assess the effect of intraoperative mild hypothermia on postoperative death and neurological deficits in people with ruptured or unruptured intracranial aneurysms. SEARCH METHODS: We updated the search in the Cochrane Stroke Group Trials Register (August 2015), the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 8), WHO International Clinical Trials Registry Platform (ICTRP; December 2015), MEDLINE (1950 to September 2015), EMBASE (1980 to September 2015), Science Citation Index (1900 to September 2015), and 11 Chinese databases (September 2015). We also searched ongoing trials registers (September 2015) and scanned reference lists of retrieved records. SELECTION CRITERIA: We included only randomised controlled trials that compared intraoperative mild hypothermia (32°C to 35°C) with control (no hypothermia) in people with ruptured or unruptured intracranial aneurysms. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials and assessed the risk of bias for each included study. We presented data as risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI). MAIN RESULTS: We included three studies, enrolling 1158 participants. Each study reported an increased rate of recovery with intraoperative mild hypothermia, but the effect sizes were not sufficient for certainty. A total of 1086 of the 1158 participants (93.8%) had good grade aneurysmal subarachnoid haemorrhage. Seventy-six of 577 participants (13.1%) who received hypothermia and 93 of 581 participants (16.0%) who did not receive hypothermia were dead or dependent (RR 0.82; 95% CI 0.62 to 1.09; RD -0.03; 95% CI -0.07 to 0.01, moderate-quality evidence) after three months.Reported unfavourable outcomes did not differ between participants with or without hypothermia. The quality of evidence for these outcomes remains unclear because the outcomes were reported in a variety of ways. No decompressive craniectomy or corticectomy was reported. Thirty-six of 577 (6.2%) participants with hypothermia and 40 of 581 (6.9%) participants without hypothermia had infarction. Thirty-four of 577 (6%) participants with hypothermia and 32 of the 581 (5.5%) participants without hypothermia had clinical vasospasm (temporary deficits).Duration of hospital stay was not reported. Only one study with 112 participants reported discharge destinations: 43 of 55 (78.2%) participants with hypothermia and 39 of 57 (68.4%) participants in the control group were discharged home. The remaining participants were discharged to other facilities.Thirty-nine of 577 (6.8%) participants with hypothermia and 39 of 581 (6.7%) participants without hypothermia had infections. Six of 577 (1%) participants with hypothermia and 6 of 581 (1%) participants without hypothermia had cardiac arrhythmia. AUTHORS' CONCLUSIONS: It remains possible that intraoperative mild hypothermia could prevent death or dependency in activities of daily living in people with good grade aneurysmal subarachnoid haemorrhage. However, the confidence intervals around this estimate include the possibility of both benefit and harm. There was insufficient information to draw any conclusions about the effects of intraoperative mild hypothermia in people with poor grade aneurysmal subarachnoid haemorrhage or without subarachnoid haemorrhage. We did not identify any reliable evidence to support the routine use of intraoperative mild hypothermia. A high-quality randomised clinical trial of intraoperative mild hypothermia for postoperative neurological deficits in people with poor grade aneurysmal subarachnoid haemorrhage might be feasible.

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.

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.

Intraoperative mild hypothermia for postoperative neurological deficits in intracranial aneurysm patients.

BACKGROUND: Rupture of an intracranial aneurysm causes aneurysmal subarachnoid haemorrhage, which is one of the most devastating clinical conditions. Clinically, it can be classified into five grades using the Hunt-Hess or World Federation of Neurological Surgeons (WFNS) scale. Grades 4 and 5 predict poor prognosis and are called 'poor grade', while grade 1, 2, and 3 are known as 'good grade'. Disturbances of intracranial homeostasis and brain metabolism are known to play certain roles in the sequelae. Hypothermia has a long history of being used to reduce metabolism rate, thereby protecting organs in cases where metabolism is disturbed and potentially harmful. OBJECTIVES: To assess the effect of intraoperative mild hypothermia on postoperative death and neurological deficits in patients with intracranial aneurysms (ruptured or unruptured). SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (September 2011), the Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 3), MEDLINE (1950 to September 2011), EMBASE (1980 to September 2011), Science Citation Index (1900 to September 2011) and 11 Chinese databases (September 2011). We also searched ongoing trials registers (September 2011) and scanned reference lists of retrieved records. SELECTION CRITERIA: We included only randomised controlled trials comparing intraoperative mild hypothermia (32°C to 35°C) with control (no hypothermia) in patients with intracranial aneurysms (ruptured or unruptured). DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials and assessed the risk of bias for each included study. We presented data as risk ratio (RR) with 95% confidence intervals (CI). MAIN RESULTS: We included three studies enrolling 1158 patients. Each study observed an increased rate of good recovery with intraoperative mild hypothermia, but the effect sizes were not sufficient for statistical significance. A total of 76 of 577 patients (13.1%) who received hypothermia and 93 of 581 patients (16.0%) who did not receive hypothermia were dead or dependent. A total of 1086 of the1158 patients (93.8%) had good-grade aneurysmal subarachnoid haemorrhage. A random-effects meta-analysis resulted in a summarised RR of 0.82 (95% CI 0.62 to 1.09, P value 0.17). In patients with poor-grade aneurysmal subarachnoid haemorrhage, one of seven in the hypothermia group and one of six in the control group were dead or dependent (RR 0.86, 95% CI 0.07 to 10.96, P value 0.91). In patients without subarachnoid haemorrhage, three of 30 patients (10%) in the hypothermia group, and four of 29 patients (13.8%) in the control group were dead or dependent (RR 0.72, 95% CI 0.18 to 2.96, P value 0.65). AUTHORS' CONCLUSIONS: In patients with good-grade aneurysmal subarachnoid haemorrhage, intraoperative mild hypothermia might prevent death or dependency in activities of daily living for a few of them. However, the confidence intervals include the possibility of both benefit and harm. There is no evidence that intraoperative mild hypothermia is harmful. This treatment should not be routinely applied. In patients with poor-grade aneurysmal subarachnoid haemorrhage or without subarachnoid haemorrhage, there are insufficient data to draw any conclusions. A high-quality randomised clinical trial of intraoperative mild hypothermia for postoperative neurological deficits in patients with poor-grade aneurysmal subarachnoid haemorrhage might be feasible.

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.