Disease-modifying treatments for primary autoimmune haemolytic anaemia.

BACKGROUND: Primary autoimmune haemolytic anaemia (AIHA) is an autoantibody mediated condition characterised by a variable disease course. A myriad of immunomodulatory agents have been employed but there is a paucity of evidence to support their use or compare their effectiveness. OBJECTIVES: To determine the effects of various disease-modifying treatment modalities in people with AHIHA. SEARCH METHODS: We searched MEDLINE (Ovid) (1946 to 2021), Embase (Ovid) (1974 to 2021), Latin American and Caribbean Health Sciences Literature (LILACS) (1982 to 2021), and the Cochrane Library (CENTRAL). Clinical trial registries and relevant conference proceedings were also reviewed. Records were included as of 7 March 2021. We did not impose any language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing immunosuppressive or immunomodulatory treatments against no treatment, placebo, or another immunosuppressive or immunomodulatory treatment, for people of all age with idiopathic AIHA. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The prioritised pre-defined outcomes included complete haematological response at 12 months, frequency of adverse events at two, six and 12 months, partial haematological response at 12 months, overall survival at six and 12 months, relapse-free survival (RFS) at six and 12 months, red blood cel (RBC) transfusion requirement after treatment at 12 months, and quality of life (QOL) as measured by validated instruments at 12 months. Based on data availability, we were only able to perform meta-analysis on frequency of complete haematological response. MAIN RESULTS: Two trials were included, enrolling a total of 104 adult participants (96 randomised) with warm AIHA in the setting of tertiary referral centres, both comparing the effectiveness between rituximab (375 mg/m2 weekly for four weeks, or 1000 mg for two doses two weeks apart) plus glucocorticoid (prednisolone 1.5 or 1mg/kg/day with taper) and glucocorticoid monotherapy. The average age of participants in the two trials were 67 and 71, respectively. One of the included studies had good methodological quality with low risk of bias, whereas the other study had high risk of performance and detection bias due to lack of blinding. Compared with glucocorticoid alone, adding rituximab may result in a large increase of complete response at 12 months (n = 96, risk ratio (RR) 2.13, 95% confidence interval (CI) 1.34 to 3.40, GRADE: low-certainty evidence). Rates of adverse effects at prespecified time-points were not reported. Limited data on partial haematological response were reported. The evidence is very uncertain about the effect of adding rituximab to glucocorticoids on partial haematological response at 12 months (n = 32; study = 1; RR 3.00, 95% CI 0.13 to 68.57; GRADE very low-certainty evidence). RBC transfusion need at 12 months was reported in one study, with four participants (mean number of packed red cell units 4.0 ± 2.82) from the rituximab group and five participants from the placebo (corticosteroid only) (mean number of packed red cell units 5.6 ± 4.15) group requiring transfusion, indicating very uncertain evidence about the effect of adding rituximab to glucocorticoids (n = 32, RR 0.80, 95% CI 0.26 to 2.45, GRADE very low-certainty evidence). The other study did not report transfusion requirement at prespecified time points but reported no difference in transfusion requirement between the two groups when comparing responders from enrolment to end of response or to the end of study follow-up (34 units versus 30 units, median [range]: 0 [1 to 6] versus 0 [1 to 5], P = 0·81). Overall survival and RFS rates at prespecified time-points were not explicitly reported in either study. Data on QOL were not available. AUTHORS' CONCLUSIONS: Available literature on the effectiveness of immunomodulatory therapy for primary AIHA is restricted to comparison between rituximab plus glucocorticoid and glucocorticoid alone, in patients with newly diagnosed warm AIHA, calling for need for additional studies. The current result suggests that combinatory therapy with rituximab and glucocorticoid may increase the rate of complete haematological response over glucocorticoid monotherapy.

Risk factors for drug allergies in Chinese children.

BACKGROUND: Drug allergy, or drug hypersensitivity, is a potentially fatal disorder, and patients labeled with drug allergies have restricted access to first-line treatments. Full knowledge of the characteristics associated with drug allergies and severe reactions during allergy evaluation is beneficial for appropriate risk stratification. OBJECTIVE: We sought to determine whether certain clinical characteristics are associated with drug allergies in Chinese children. METHODS: Charts were reviewed for ethnic Chinese patients less than 18 years old referred to our tertiary allergy center for suspected drug allergies and completed skin and drug provocative testing between 2005 to 2017. Univariate and multivariate analyses were performed on the age of onset of drug allergies, gender, and other atopy versus drug allergies. RESULTS: Out of 75 children, 18 (24%) had IgE-mediated drug allergies, while 8 (10.7%) had delayed drug hypersensitivities, with a cumulative 26 subjects (34.7%) with any drug hypersensitivity. There were positive independent associations between drug hypersensitivities onset age vs IgE-mediated drug allergies (odds ratio (OR) = 14.9, 95% confidence intervals (CIs) = 1.5-148.3, P = 0.017) and between male gender and IgE-mediated drug allergies (OR = 4.4, CIs = 1.2-16.4, P = 0.019). Age 13 years was the best cut-off for IgE-mediated drug allergies according to the receiver operating characteristic curve (P = 0.026). Older age group (OR = 24.0, CIs = 1.4-417.8, P = 0.024) and atopic dermatitis (OR = 8.2, CIs = 1.4-49.8, P = 0.015) were correlated with delayed drug hypersensitivities. CONCLUSIONS: While several previous studies suggested a higher prevalence of IgE-mediated drug allergies in younger adult females, older boys were more likely to have drug allergies for Chinese children.

Urate oxidase for the prevention and treatment of tumour lysis syndrome in children with cancer.

BACKGROUND: Tumour lysis syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Previous reviews did not find clear evidence of benefit of urate oxidase in children with cancer. This review is the second update of a previously published Cochrane review. OBJECTIVES: To assess the effects and safety of urate oxidase for the prevention and treatment of TLS in children with malignancies. SEARCH METHODS: In March 2016 we searched CENTRAL, MEDLINE, Embase, and CINAHL. In addition, we searched the reference lists of all identified relevant papers, trials registers and other databases. We also screened conference proceedings and we contacted experts in the field and the manufacturer of rasburicase, Sanofi-aventis. SELECTION CRITERIA: Randomised controlled trials (RCT) and controlled clinical trials (CCT) of urate oxidase for the prevention or treatment of TLS in children under 18 years with any malignancy. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted trial data and assessed individual trial quality. We used risk ratios (RR) for dichotomous data and mean difference (MD) for continuous data. MAIN RESULTS: We included seven trials, involving 471 participants in the treatment groups and 603 participants in the control groups. No new studies were identified in the update. One RCT and five CCTs compared urate oxidase and allopurinol. Three trials tested Uricozyme, and three trials tested rasburicase for the prevention of TLS.The RCT did not evaluate the primary outcome (incidence of clinical TLS). It showed no clear evidence of a difference in mortality (both all-cause mortality (Fisher's exact test P = 0.23) and mortality due to TLS (no deaths in either group)), renal failure (Fisher's exact test P = 0.46), and adverse effects between the treatment and the control groups (Fisher's exact test P = 1.0). The frequency of normalisation of uric acid at four hours (10 out of 10 participants in the treatment group versus zero out of nine participants in the control group, Fisher's exact test P < 0.001) and area under the curve of uric acid at four days (MD -201.00 mg/dLhr, 95% CI -258.05 mg/dLhr to -143.95 mg/dLhr; P < 0.00001) were significantly better in the treatment group.One CCT evaluated the primary outcome; no clear evidence of a difference was identified between the treatment and the control groups (RR 0.77, 95% CI 0.44 to 1.33; P = 0.34). Pooled results of three CCTs showed significantly lower mortality due to TLS in the treatment group (RR 0.05, 95% CI 0.00 to 0.89; P = 0.04); no clear evidence of a difference in all-cause mortality was identified between the groups (RR 0.19, 95% CI 0.01 to 3.42; P = 0.26). Pooled results from five CCTs showed significantly lower incidence of renal failure in the treatment group (RR 0.26, 95% CI 0.08 to 0.89; P = 0.03). Results of CCTs also showed significantly lower uric acid in the treatment group at two days (three CCTs: MD -3.80 mg/dL, 95% CI -7.37 mg/dL to -0.24 mg/dL; P = 0.04), three days (two CCTs: MD -3.13 mg/dL, 95% CI -6.12 mg/dL to -0.14 mg/dL; P = 0.04), four days (two CCTs: MD -4.60 mg/dL, 95% CI -6.39 mg/dL to -2.81 mg/dL; P < 0.00001), and seven days (one CCT: MD -1.74 mg/dL, 95% CI -3.01 mg/dL to -0.47 mg/dL; P = 0.007) after therapy, but not one day (three CCTs: MD -3.00 mg/dL, 95% CI -7.61 mg/dL to 1.60 mg/dL; P = 0.2), five days (one CCT: MD -1.02 mg/dL, 95% CI -2.24 mg/dL to 0.20 mg/dL; P = 0.1), and 12 days (one CCT: MD -0.80 mg/dL, 95% CI -2.51 mg/dL to 0.91 mg/dL; P = 0.36) after therapy. Pooled results from three CCTs showed higher frequency of adverse effects in participants who received urate oxidase (RR 9.10, 95% CI 1.29 to 64.00; P = 0.03).Another included RCT, with 30 participants, compared different doses of rasburicase (0.2 mg/kg versus 0.15 mg/kg). The primary outcome was not evaluated. No clear evidence of a difference in mortality (all-cause mortality (Fisher's exact test P = 1.0) and mortality due to TLS (no deaths in both groups)) and renal failure (no renal failure in both groups) was identified. It demonstrated no clear evidence of a difference in uric acid normalisation (RR 1.07, 95% CI 0.89 to 1.28; P = 0.49) and uric acid level at four hours (MD 8.10%, 95% CI -0.99% to 17.19%; P = 0.08). Common adverse events of urate oxidase included hypersensitivity, haemolysis, and anaemia, but no clear evidence of a difference between treatment groups was identified (RR 0.54, 95% CI 0.12 to 2.48; P = 0.42).The quality of evidence ranks from very low to low because of imprecise results, and all included trials were highly susceptible to biases. AUTHORS' CONCLUSIONS: Although urate oxidase might be effective in reducing serum uric acid, it is unclear whether it reduces clinical TLS, renal failure, or mortality. Adverse effects might be more common for urate oxidase compared with allopurinol. Clinicians should weigh the potential benefits of reducing uric acid and uncertain benefits of preventing mortality or renal failure from TLS against the potential risk of adverse effects.

Optimal stem cell source for allogeneic stem cell transplantation for hematological malignancies.

Hematopoietic stem cell transplant (HSCT) is a standard treatment for many hematological malignancies. Three different sources of stem cells, namely bone marrow (BM), peripheral blood stem cells (PBSC) and cord blood (CB) can be used for HSCT, and each has its own advantages and disadvantages. Randomized controlled trials (RCTs) suggest that there is no significant survival advantage of PBSC over BM in Human Leukocyte Antigen-matched sibling transplant for adult patients with hematological malignancies. PBSC transplant probably results in lower risk of relapse and hence better disease-free survival, especially in patients with high risk disease at the expense of higher risks of both severe acute and chronic graft-versus-host disease (GVHD). In the unrelated donor setting, the only RCT available suggests that PBSC and BM result in comparable overall and disease-free survivals in patients with hematological malignancies; and PBSC transplant results in lower risk of graft failure and higher risk of chronic GVHD. High level evidence is not available for CB in comparison to BM or PBSC. The risks and benefits of different sources of stem cells likely change with different conditioning regimen, strategies for prophylaxis and treatment of GVHD and manipulation of grafts. The recent success and rapid advance of double CB transplant and haploidentical BM and PBSC transplants further complicate the selection of stem cell source. Optimal selection requires careful weighing of the risks and benefits of different stem cell source for each individual recipient and donor. Detailed counseling of patient and donor regarding risks and benefits in the specific context of the patient and transplant method is essential for informed decision making.

Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: Prophylaxis and treatment controversies.

Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome, is a major complication of hematopoietic stem cell transplantation and it carries a high mortality. Prophylaxis for hepatic VOD is commonly given to transplant recipients from the start of conditioning through the early weeks of transplant. However, high quality evidence from randomized controlled trials is scarce with small sample sizes and the trials yielded conflicting results. Although various treatment options for hepatic VOD are available, most have not undergone stringent evaluation with randomized controlled trial and therefore it remains uncertain which treatment offers real benefit. It remains controversial whether VOD prophylaxis should be given, which prophylactic therapy should be given, who should receive prophylaxis, and what treatment should be offered once VOD is established.

Complementary and miscellaneous interventions for nocturnal enuresis in children.

BACKGROUND: Nocturnal enuresis (bedwetting) is a socially disruptive and stressful condition which affects around 15% to 20% of five year olds, and up to 2% of young adults. OBJECTIVES: To assess the effects of complementary interventions and others such as surgery or diet on nocturnal enuresis in children, and to compare them with other interventions. SEARCH METHODS: We searched PubMed (1950 to June 2010), EMBASE (1980 to June 2010), the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS) (1984 to June 2010), Chinese Biomedical Literature Database (CBM) (1975 to June 2010), China National Knowledge Infrastructure (CNKI) (1979 to June 2010), VIP database (1989 to June 2010), and the reference lists of relevant articles, all last searched 26 June 2010. No language restriction was used. SELECTION CRITERIA: All randomised or quasi-randomised trials of complementary and other miscellaneous interventions for nocturnal enuresis in children were included except those focused solely on daytime wetting. Comparison interventions could include no treatment, placebo or sham treatment, alarms, simple behavioural treatment, desmopressin, imipramine and miscellaneous other drugs and interventions. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the quality of the eligible trials, and extracted data. MAIN RESULTS: In 24 randomised controlled trials, 2334 children were studied, of whom 1283 received a complementary intervention. The quality of the trials was poor: 5 trials were quasi-randomised, 5 showed differences at baseline and 17 lacked follow up data.The outcome was better after hypnosis than imipramine in one trial (relative risk (RR) for failure or relapse after stopping treatment 0.42, 95% confidence interval (CI) 0.23 to 0.78). Psychotherapy appeared to be better in terms of fewer children failing or relapsing than both alarm (RR 0.28, 95% CI 0.09 to 0.85) and rewards (RR 0.29, 95%CI 0.09 to 0.90) but this depended on data from only one trial. Medicinal herbs had better results than desmopressin in one trial (RR for failure or relapse after stopping treatment 0.35, 95% CI 0.14 to 0.85). Acupuncture had better results than sham control acupuncture (RR for failure or relapse after stopping treatment 0.67, 95% CI 0.48 to 0.94) in a further trial. Active chiropractic adjustment had better results than sham adjustment (RR for failure to improve 0.76, 95% CI 0.60 to 0.95). However, each of these findings came from small single trials, and must be verified in further trials. The findings for diet and faradization were unreliable, and there were no trials including homeopathy or surgery. AUTHORS' CONCLUSIONS: There was weak evidence to support the use of hypnosis, psychotherapy, acupuncture, chiropractic and medicinal herbs but it was provided in each case by single small trials, some of dubious methodological rigour. Robust randomised trials are required with efficacy, cost-effectiveness and adverse effects clearly reported.

Acupuncture for autism spectrum disorders (ASD).

BACKGROUND: Autism spectrum disorders (ASD) are characterized by impairment in social interaction, impairment in communication and lack of flexibility of thought and behavior. Acupuncture, which involves the use of needles or pressure to specific points on the body, is used widely in Traditional Chinese Medicine and increasingly within a western medical paradigm. It has sometimes been used as a treatment aimed at improving ASD symptoms and outcomes, but its clinical effectiveness and safety has not been rigorously reviewed. OBJECTIVES: To determine the effectiveness of acupuncture for people with ASD in improving core autistic features, as well as communication, cognition, overall functioning and quality of life, and to establish if it has any adverse effects. SEARCH STRATEGY: We searched the following databases on 30 September 2010: CENTRAL (The Cochrane Library, 2010, Issue 3), MEDLINE (1950 to September 2010 Week 2), EMBASE (1980 to 2010 Week 38), PsycINFO, CINAHL, China Journal Full-text Database, China Master Theses Full-text Database, China Doctor Dissertation Full-text Database, China Proceedings of Conference Database, Index to Taiwan Periodical Literature System, metaRegister of Controlled Trials and the Chinese Clinical Trials Registry. We also searched AMED (26 February 2009) and Dissertation Abstracts International (3 March 2009), but these were no longer available to the authors or editorial base at the date of the most recent search. TCMLARS (Traditional Chinese Medical Literature Analysis and Retrieval System) was last searched on 3 March 2009. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials. We included studies comparing an acupuncture group with at least one control group that used no treatment, placebo or sham acupuncture treatment in people with ASD. We excluded trials that compared different forms of acupuncture or compared acupuncture with another treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted trial data and assessed the risk of bias in the trials. We used relative risk (RR) for dichotomous data and mean difference (MD) for continuous data. MAIN RESULTS: We included 10 trials that involved 390 children with ASD. The age range was three to 18 years and the treatment duration ranged from four weeks to nine months. The studies were carried out in Hong Kong, mainland China and Egypt.Two trials compared needle acupuncture with sham acupuncture and found no difference in the primary outcome of core autistic features (RFRLRS total score: MD 0.09; 95% CI -0.03 to 0.21, P = 0.16), although results suggested needle acupuncture might be associated with improvement in some aspects of the secondary outcomes of communication and linguistic ability, cognitive function and global functioning.Six trials compared needle acupuncture plus conventional treatment with conventional treatment alone. The trials used different primary outcome measures and most could not demonstrate effectiveness of acupuncture in improving core autistic features in general, though one trial reported patients in the acupuncture group were more likely to have improvement on the Autism Behavior Checklist (RR 1.53; 95% CI 1.09 to 2.16, P = 0.02) and had slightly better post-treatment total scores (MD -5.53; 95% CI -10.76 to -0.31, P = 0.04). There was no evidence that acupuncture was effective for the secondary outcome of communication and linguistic ability, though there seemed to be some benefit for the secondary outcomes of cognitive function and global functioning.Two trials compared acupressure plus conventional treatment with conventional treatment alone and did not report on the primary outcome. Individual study results suggested there may be some benefit from acupressure for certain aspects of the secondary outcomes of communication and linguistic ability, cognitive function and global functioning.Four trials reported some adverse effects, though there was little quantitative information, and at times both intervention and control groups experienced them. Adverse effects noted included bleeding, crying due to fear or pain, irritability, sleep disturbance and increased hyperactivity. None of the trials reported on quality of life.There are a number of problems with the evidence base: the trials were few in number and included only children; six of the trials were at high risk of bias; they were heterogeneous in terms of participants and intervention; they were of short duration and follow-up; they reported inconsistent and imprecise results, and, due to carrying out large numbers of analyses, they were at risk of false positivity. AUTHORS' CONCLUSIONS: Current evidence does not support the use of acupuncture for treatment of ASD. There is no conclusive evidence that acupuncture is effective for treatment of ASD in children and no RCTs have been carried out with adults. Further high quality trials of larger size and longer follow-up are needed.

Medical interventions for treating anthracycline-induced symptomatic and asymptomatic cardiotoxicity during and after treatment for childhood cancer.

BACKGROUND: Anthracyclines are frequently used chemotherapeutic agents for childhood cancer that can cause cardiotoxicity during and after treatment. Although several medical interventions in adults with symptomatic or asymptomatic cardiac dysfunction due to other causes are beneficial, it is not known if the same treatments are effective for childhood cancer patients and survivors with anthracycline-induced cardiotoxicity. OBJECTIVES: To compare the effect of medical interventions on anthracycline-induced cardiotoxicity in childhood cancer patients or survivors with the effect of placebo, other medical interventions or no treatment. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2011, issue 1), MEDLINE/PubMed (1949 to May 2011) and EMBASE/Ovid (1980 to May 2011) for potentially relevant articles. We additionally searched reference lists of relevant articles, conference proceedings and ongoing trial databases. SELECTION CRITERIA: Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) comparing the effectiveness of medical interventions to treat anthracycline-induced cardiotoxicity with either placebo, other medical interventions or no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently performed the study selection. One review author performed the data extraction and 'Risk of bias' assessments which were checked by another review author. MAIN RESULTS: We identified two RCTs. One trial (135 patients) compared enalapril with placebo in childhood cancer survivors with asymptomatic anthracycline induced cardiac dysfunction. The other trial (68 patients) compared a two-week treatment of phosphocreatine with a control treatment (vitamin C, ATP, vitamin E, oral coenzyme Q10) in leukaemia patients with anthracycline-induced cardiotoxicity. Both studies had methodological limitations.The RCT on enalapril showed no (statistically) significant differences in overall survival, mortality due to heart failure, development of clinical heart failure and quality of life between treatment and control group. A post-hoc analysis showed a decrease (i.e. improvement) in one measure of cardiac function (left ventricular end systolic wall stress (LVESWS): -8.62% change) compared with placebo (+1.66% change) in the first year of treatment (P = 0.036), but not afterwards. Patients treated with enalapril had a higher risk of dizziness or hypotension (RR 7.17, 95% CI 1.71 to 30.17) and fatigue (Fisher's exact test, P = 0.013).The RCT on phosphocreatine found no differences in overall survival, mortality due to heart failure, echocardiographic cardiac function and adverse events between treatment and control group. AUTHORS' CONCLUSIONS: For the effect of enalapril in childhood cancer survivors with asymptomatic cardiac dysfunction, only one RCT is available. Although there is some evidence that enalapril temporarily improves one parameter of cardiac function (LVESWS), it is unclear whether it improves clinical outcomes. Enalapril was associated with a higher risk of dizziness or hypotension and fatigue. Clinicians should weigh the possible benefits with the known side-effects of enalapril in childhood cancer survivors with asymptomatic anthracycline-induced cardiotoxicity.For the effect of phosphocreatine in childhood cancer patients with anthracycline-induced cardiotoxicity, only one RCT is available. Limited data with a high risk of bias showed no significant difference between phosphocreatine and control treatment on echocardiographic function and clinical outcomes.We did not identify any RCTs or CCTs studying other medical interventions for symptomatic or asymptomatic cardiotoxicity in childhood cancer patients or survivors.High-quality studies should be performed.

Acupuncture for acute management and rehabilitation of traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) can be life threatening depending on the severity of the insult to the brain. It can also cause a range of debilitating sequelae which require cognitive, motor, communication, emotional, or behavioral rehabilitation of varying intensity and duration. A number of studies conducted and published in China have suggested that acupuncture may be beneficial in the acute treatment and rehabilitation of TBI. OBJECTIVES: To determine the efficacy and safety of acupuncture in the acute management or rehabilitation (or both) of patients with a TBI, including cognitive, neurological, motor, communication, emotional, or behavioral complications, or a combination of such complications. SEARCH STRATEGY: We searched the Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials 2008, Issue 2 (The Cochrane Library), MEDLINE, EMBASE, CINAHL, AMED, PsycINFO and others. We also searched the Chinese Acupuncture Studies Register, the Studies Register of the Cochrane Complementary Medicine Field, NCCAM, and NIH Clinical Studies Database. Three major Mainland Chinese academic literature databases (CNKI, VIP and Wang Fang Data) were also searched using keywords in simplified Chinese. Searches were completed in December 2009. SELECTION CRITERIA: Randomized controlled studies evaluating different variants of acupuncture and involving participants of any age who had suffered a TBI. Included trials compared acupuncture with placebo or sham treatment, or acupuncture plus other treatments compared with the same other treatments. We excluded trials that only compared different variants of acupuncture or compared acupuncture alone against other treatments alone, as they did not yield the net effect of acupuncture. DATA COLLECTION AND ANALYSIS: Two review authors identified potential articles from the literature search and extracted data independently using a data extraction form. We performed methodological assessment of included studies using the Cochrane Collaboration's tool for assessing risk of bias. We were unable to perform quantitative data analysis due to insufficient included studies and available data. MAIN RESULTS: Four RCTs, including 294 participants, reported outcomes specified by this review. Three investigated electro-acupuncture for TBI while one investigated acupuncture for acute TBI. The results seem to suggest that acupuncture is efficacious for these indications, however the low methodological quality of these studies renders the results questionable. No adverse effects of acupuncture were reported in any of the studies. AUTHORS' CONCLUSIONS: The low methodological quality of the included studies does not allow us to make conclusive judgments on the efficacy and safety of acupuncture in either the acute treatment and/or rehabilitation of TBI. Its beneficial role for these indications remains uncertain. Further research with high quality trials is required.

Vaccines for prophylaxis of viral infections in patients with hematological malignancies.

BACKGROUND: Viral infections cause significant morbidity and mortality in patients with hematological malignancies. It remains uncertain whether viral vaccinations in these patients are supported by good evidence. OBJECTIVES: We aimed to determine the effectiveness and safety of viral vaccines in patients with hematological malignancies. SEARCH STRATEGY: We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL (June 2010), reference lists of relevant papers, abstracts from scientific meetings and contacted vaccine manufacturers. SELECTION CRITERIA: Randomized controlled trials (RCTs) evaluating viral vaccines in patients with hematological malignancies were included. DATA COLLECTION AND ANALYSIS: Relative risk (RR) was used for binary data and mean difference (MD) for continuous data. Primary outcome was incidence of infection. Secondary outcomes were mortality, incidence of complications and severe viral infection, hospitalization, immune response and adverse effects. Fixed-effect model was used in meta-analyses. MAIN RESULTS: Eight RCTs were included, with 305 patients in the intervention groups and 288 in the control groups. They evaluated heat-inactivated varicella zoster virus (VZV) vaccine (two trials), influenza vaccines (five trials) and inactivated poliovirus vaccine (IPV) (one trial). Seven trials had high and one trial had moderate risk of bias.VZV vaccine might reduce herpes zoster compared to no vaccine (RR 0.54, 95% CI 0.3 to 1.0, P=0.05), but not statistically significant. Vaccination also demonstrated efficacy in immune response but frequently caused local adverse effects. One trial reported severity score of zoster, which favored vaccination (MD 2.6, 95% CI 0.94 to 4.26, P=0.002).Two RCTs compared inactivated influenza vaccine with no vaccine and reported lower risk of lower respiratory infections (RR 0.39, 95% CI 0.19 to 0.78, P=0.008) and hospitalization (RR 0.17, 95% CI 0.09 to 0.31, P<0.00001) in vaccine recipients. However, vaccine recipients more frequently experienced irritability and local adverse effects. There was no significant difference in seroconversion between one and two doses of influenza vaccine (one trial), or between recombinant and standard influenza vaccine (one trial), or influenza vaccine given with or without re-induction chemotherapy (one trial).The IPV trial comparing vaccination starting at 6 versus 18 months after stem cell transplant (SCT) found no significant difference in seroconversion. AUTHORS' CONCLUSIONS: Inactivated VZV vaccine might reduce zoster severity in adult SCT recipients. Inactivated influenza vaccine might reduce respiratory infections and hospitalization in adults with multiple myeloma or children with leukemia or lymphoma. However, the quality of evidence is low. Local adverse effects occur frequently. Further high-quality RCTs are needed.

Urate oxidase for the prevention and treatment of tumor lysis syndrome in children with cancer.

BACKGROUND: Tumor lysis syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Preliminary reports suggest that urate oxidase is highly effective in reducing serum uric acid. It is uncertain whether high quality evidence exists to support its routine use in children with malignancies. OBJECTIVES: We aimed to determine the effectiveness and safety of urate oxidase in the prevention and treatment of TLS in children with malignancies. SEARCH STRATEGY: We performed a comprehensive search of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library issue 2, 2009), MEDLINE (1966 to 2009), EMBASE (1980 to 2009) and CINAHL (1982 to 2009). SELECTION CRITERIA: Randomized controlled trials (RCT) and controlled clinical trials (CCT) evaluating urate oxidase for the prevention or treatment of TLS in children under 18 years with any malignancy. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted trial data and assessed individual trial quality. We used relative risk (RR) for binary data and mean difference (MD) for continuous data. MAIN RESULTS: We included five trials, involved 336 patients in the treatment groups and 458 patients in the control groups. One RCT and three CCTs compared urate oxidase and allopurinol. Two trials tested Uricozyme and two tested rasburicase for the prevention of TLS. The RCT showed no significant difference in mortality or renal failure between the treatment and the control groups. The frequency of normalization of uric acid (RR 19.09, 95% CI 1.28 to 285.41) and area under curve of uric acid (MD -201, 95% CI to -258.05 to -143.95) were significantly better in the treatment group. One patient developed hemolysis. One CCT reported significantly lower mortality due to TLS (RR 0.05, 95% CI 0.00 to 0.89) and lower incidence of renal failure (RR 0.13, 95% CI 0.05 to 0.35) in the treatment group. Another CCT found significantly lower uric acid in the treatment group at 72 hours (MD -98.33, 95% CI -170.66 to -26) and 168 hours (MD -103.67, 95% CI -179.00 to -28.34). All included trials are highly susceptible to biases.Another included RCT with 30 patients compared different doses of rasburicase (0.2 mg/kg versus 0.15 mg/kg), which demonstrated similar efficacy in the reduction of uric acid. Adverse events occurred in 20% of patients, including hemolysis, hypersensitivity and anemia. AUTHORS' CONCLUSIONS: Although urate oxidase might be effective in reducing serum uric acid, it is still unclear whether this translates into a reduction in mortality or renal failure. Clinicians should weigh the potential benefits of reducing uric acid and uncertain benefits of preventing renal failure or mortality from TLS against the potential risk of adverse effects.