Moxibustion for alleviating side effects of chemotherapy or radiotherapy in people with cancer.

BACKGROUND: Moxibustion, a common treatment in traditional Chinese medicine, involves burning herbal preparations containing Artemisia vulgaris on or above the skin at acupuncture points. Its intended effect is to enhance body function, and it could reduce the side effects of chemotherapy or radiotherapy and improve quality of life (QoL) in people with cancer. OBJECTIVES: To assess the effects of moxibustion for alleviating side effects associated with chemotherapy, radiotherapy or both in people with cancer. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE via Ovid, Embase via Ovid and AMED (Allied and Complementary Medicine Database) from their inception to February 2018. We also searched databases in China including the Chinese BioMedical Literature Database (CBM), Chinese Medical Current Contents (CMCC), TCMonline, Chinese Dissertation Database (CDDB), China Medical Academic Conference (CMAC) and Index to Chinese Periodical Literature from inception to August 2017. Registries for clinical trials and other resources were also searched. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing moxibustion treatment, including moxa cone and moxa stick, versus sham, no treatment or conventional treatment. DATA COLLECTION AND ANALYSIS: Two review authors (HWZ and FC) independently extracted data on study design, participants, treatment and control intervention, and outcome measures, and they also assessed risk of bias in the included studies. We performed meta-analyses, expressing dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD), with 95% confidence intervals (CI). MAIN RESULTS: We included 29 RCTs involving 2569 participants. Five RCTs compared moxibustion versus no treatment, 15 compared moxibustion plus conventional treatment versus conventional treatment, one compared moxibustion versus sham moxibustion, and eight compared moxibustion versus conventional medicine. The overall risk of bias was high in 18 studies and unclear in 11 studies. Studies measured outcomes in various ways, and we could rarely pool data.Moxibustion versus no treatment: low-certainty evidence from single small studies suggested that moxibustion was associated with higher white blood cell counts (MD 1.77 × 109/L; 95% CI 0.76 to 2.78; 80 participants, low-certainty evidence) and higher serum haemoglobin concentrations (MD 1.33 g/L; 95% CI 0.59 to 2.07; 66 participants, low-certainty evidence) in people with cancer, during or after chemotherapy/radiotherapy, compared with no treatment. There was no evidence of an effect on leukopenia (RR 0.50, 95% CI 0.10 to 2.56; 72 participants, low-certainty evidence) between study groups. The effects on immune function (CD3, CD4, and CD8 counts) were inconsistent.Moxibustion versus sham moxibustion: low-certainty evidence from one study (50 participants) suggested that moxibustion improved QoL (measured as the score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)) compared with sham treatment (MD 14.88 points; 95% CI 4.83 to 24.93). Low-certainty evidence from this study also showed reductions in symptom scores for nausea and vomiting (MD -38.57 points, 95% CI -48.67 to -28.47) and diarrhoea (MD -13.81, 95% CI -27.52 to -0.10), and higher mean white blood cell count (MD 1.72 × 109/L, 95% CI 0.97 to 2.47), serum haemoglobin (MD 2.06 g/L, 95% CI 1.26 to 2.86) and platelets (MD 210.79 × 109/L, 95% CI 167.02 to 254.56) when compared with sham moxibustion.Moxibustion versus conventional medicines: low-certainty evidence from one study (90 participants) suggested that moxibustion improved WBC count eight days after treatment ended compared with conventional medicines (MD 0.40 × 109/L; 95% CI 0.15 to 0.65). Low-certainty evidence from two studies (235 participants) suggested moxibustion improved serum haemoglobin concentrations compared with conventional medicines (MD 10.28 g/L; 95% CI 4.51 to 16.05).Moxibustion plus conventional treatment versus conventional treatment alone: low-certainty evidence showed that moxibustion plus conventional treatment was associated with lower incidence and severity of leukopenia (WHO grade 3 to 4) (RR 0.14, 95% CI 0.01 to 2.64; 1 study, 56 participants), higher QoL scores on the EORTC QLQ-C30 (MD 8.85 points, 95% CI 4.25 to 13.46; 3 studies, 134 participants, I² = 26%), lower symptom scores for nausea and vomiting (RR 0.43, 95% CI 0.25 to 0.74; 7 studies, 801participants; I² = 19%), higher white blood cell counts (data not pooled due to heterogeneity), higher serum haemoglobin (MD 3.97 g/L, 95% CI 1.40 to 6.53; 2 studies, 142 participants, I² = 0%). There was no difference in platelet counts between the two groups (MD 13.48 × 109/L; 95% CI -16.00 to 42.95; 2 studies, 142 participants; I² = 34%).Most included studies did not report related adverse events, such as burning or allergic reactions. AUTHORS' CONCLUSIONS: Limited, low-certainty evidence suggests that moxibustion treatment may help to reduce the haematological and gastrointestinal toxicities of chemotherapy or radiotherapy, improving QoL in people with cancer; however, the evidence is not conclusive, and we cannot rule out benefits or risks with this treatment. High-quality studies that report adverse effects are needed.

Prediction Models of Mortality in Acute Pancreatitis in Adults: A Systematic Review.

BACKGROUND: Acute pancreatitis (AP) varies in severity, prompting development of systems aimed at predicting prognosis to help guide therapy. Although several prediction approaches are available, their test characteristics and clinical utility are not completely understood. PURPOSE: To evaluate the test characteristics (prognostic accuracy, incremental predictive value) and clinical utility (effect on patient outcomes) of severity scores for predicting mortality in AP. DATA SOURCES: Ovid MEDLINE and EMBASE (inception to 3 May 2016). STUDY SELECTION: Longitudinal studies, in any language, that evaluated the prognostic value of at least 1 clinical severity score in AP. DATA EXTRACTION: Dual data extraction and quality assessment. DATA SYNTHESIS: Of 4039 citations screened, 94 unique studies evaluating 18 scores in 53 547 patients met the inclusion criteria. All studies provided data on prognostic accuracy, whereas 6 provided data on incremental predictive values. Most scores demonstrated low prognostic accuracy. The Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Ranson criteria were studied most extensively. The median sensitivity and specificity of APACHE II at a threshold of 7 were 100% (range, 68% to 100%) and 63% (range, 21% to 96%), respectively, and those of the Ranson criteria at a threshold of 2 were 90% (range, 0% to 100%) and 67% (range, 14% to 97%), respectively. Estimates of sensitivity were based on relatively few patients. Evidence was limited regarding the incremental predictive value of the scoring systems or their effect on patient outcomes. LIMITATION: Substantial clinical heterogeneity and inadequate methodological and reporting quality precluded a meta-analysis. CONCLUSION: The test characteristics and clinical utility of AP severity scores remain uncertain. Additional studies with improved methodological rigor are needed, and the development of new scoring systems may be justified. PRIMARY FUNDING SOURCE: Global Scholarship Programme for Research Excellence for 2014 to 2015, The Chinese University of Hong Kong.

Acupuncture for stroke rehabilitation.

BACKGROUND: Stroke is the second most common cause of death in the world and in China it has now become the main cause of death. It is also a main cause of adult disability and dependency. Acupuncture for stroke has been used in China for hundreds of years and is increasingly practiced in some Western countries. This is an update of the Cochrane review originally published in 2006 . OBJECTIVES: To determine the efficacy and safety of acupuncture therapy in people with subacute and chronic stroke. We intended to test the following hypotheses: 1) acupuncture can reduce the risk of death or dependency in people with subacute and chronic stroke at the end of treatment and at follow-up; 2) acupuncture can improve neurological deficit and quality of life after treatment and at the end of follow-up; 3) acupuncture can reduce the number of people requiring institutional care; and 4) acupuncture is not associated with any intolerable adverse effects. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane Library 2015, Issue 7), MEDLINE (1966 to July 2015, Ovid), EMBASE (1980 to July 2015, Ovid), CINAHL (1982 to July 2015, EBSCO), and AMED (1985 to July 2015, Ovid). We also searched the following four Chinese medical databases: China Biological Medicine Database (July 2015); Chinese Science and Technique Journals Database (July 2015); China National Infrastructure (July 2015), and Wan Fang database (July 2015). SELECTION CRITERIA: Truly randomised unconfounded clinical trials among people with ischaemic or haemorrhagic stroke, in the subacute or chronic stage, comparing acupuncture involving needling with placebo acupuncture, sham acupuncture, or no acupuncture. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed quality, extracted and cross-checked the data. MAIN RESULTS: We included 31 trials with a total of 2257 participants in the subacute or chronic stages of stroke. The methodological quality of most of the included trials was not high. The quality of evidence for the main outcomes was low or very low based on the assessment by the system of Grades of Recommendation, Assessment, Development and Evaluation (GRADE).Two trials compared real acupuncture plus baseline treatment with sham acupuncture plus baseline treatment. There was no evidence of differences in the changes of motor function and quality of life between real acupuncture and sham acupuncture for people with stroke in the convalescent stage.Twenty-nine trials compared acupuncture plus baseline treatment versus baseline treatment alone. Compared with no acupuncture, for people with stroke in the convalescent phase, acupuncture had beneficial effects on the improvement of dependency (activity of daily living) measured by Barthel Index (nine trials, 616 participants; mean difference (MD) 9.19, 95% confidence interval (CI) 4.34 to 14.05; GRADE very low), global neurological deficiency (seven trials, 543 participants; odds ratio (OR) 3.89, 95% CI 1.78 to 8.49; GRADE low), and specific neurological impairments including motor function measured by Fugl-Meyer Assessment (four trials, 245 participants; MD 6.16, 95% CI 4.20 to 8.11; GRADE low), cognitive function measured by the Mini-Mental State Examination (five trials, 278 participants; MD 2.54, 95% CI 0.03 to 5.05; GRADE very low), depression measured by the Hamilton Depression Scale (six trials, 552 participants; MD -2.58, 95% CI -3.28 to -1.87; GRADE very low), swallowing function measured by drinking test (two trials, 200 participants; MD -1.11, 95% CI -2.08 to -0.14; GRADE very low), and pain measured by the Visual Analogue Scale (two trials, 118 participants; MD -2.88, 95% CI -3.68 to -2.09; GRADE low). Sickness caused by acupuncture and intolerance of pain at acupoints were reported in a few participants with stroke in the acupuncture groups. No data on death, the proportion of people requiring institutional care or requiring extensive family support, and all-cause mortality were available in all included trials. AUTHORS' CONCLUSIONS: From the available evidence, acupuncture may have beneficial effects on improving dependency, global neurological deficiency, and some specific neurological impairments for people with stroke in the convalescent stage, with no obvious serious adverse events. However, most included trials were of inadequate quality and size. There is, therefore, inadequate evidence to draw any conclusions about its routine use. Rigorously designed, randomised, multi-centre, large sample trials of acupuncture for stroke are needed to further assess its effects.

Yoga for asthma.

BACKGROUND: Asthma is a common chronic inflammatory disorder affecting about 300 million people worldwide. As a holistic therapy, yoga has the potential to relieve both the physical and psychological suffering of people with asthma, and its popularity has expanded globally. A number of clinical trials have been carried out to evaluate the effects of yoga practice, with inconsistent results. OBJECTIVES: To assess the effects of yoga in people with asthma. SEARCH METHODS: We systematically searched the Cochrane Airways Group Register of Trials, which is derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, and PsycINFO, and handsearching of respiratory journals and meeting abstracts. We also searched PEDro. We searched ClinicalTrials.gov and the WHO ICTRP search portal. We searched all databases from their inception to 22 July 2015, and used no restriction on language of publication. We checked the reference lists of eligible studies and relevant review articles for additional studies. We attempted to contact investigators of eligible studies and experts in the field to learn of other published and unpublished studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared yoga with usual care (or no intervention) or sham intervention in people with asthma and reported at least one of the following outcomes: quality of life, asthma symptom score, asthma control, lung function measures, asthma medication usage, and adverse events. DATA COLLECTION AND ANALYSIS: We extracted bibliographic information, characteristics of participants, characteristics of interventions and controls, characteristics of methodology, and results for the outcomes of our interest from eligible studies. For continuous outcomes, we used mean difference (MD) with 95% confidence interval (CI) to denote the treatment effects, if the outcomes were measured by the same scale across studies. Alternatively, if the outcomes were measured by different scales across studies, we used standardised mean difference (SMD) with 95% CI. For dichotomous outcomes, we used risk ratio (RR) with 95% CI to measure the treatment effects. We performed meta-analysis with Review Manager 5.3. We used the fixed-effect model to pool the data, unless there was substantial heterogeneity among studies, in which case we used the random-effects model instead. For outcomes inappropriate or impossible to pool quantitatively, we conducted a descriptive analysis and summarised the findings narratively. MAIN RESULTS: We included 15 RCTs with a total of 1048 participants. Most of the trials were conducted in India, followed by Europe and the United States. The majority of participants were adults of both sexes with mild to moderate asthma for six months to more than 23 years. Five studies included yoga breathing alone, while the other studies assessed yoga interventions that included breathing, posture, and meditation. Interventions lasted from two weeks to 54 months, for no more than six months in the majority of studies. The risk of bias was low across all domains in one study and unclear or high in at least one domain for the remainder.There was some evidence that yoga may improve quality of life (MD in Asthma Quality of Life Questionnaire (AQLQ) score per item 0.57 units on a 7-point scale, 95% CI 0.37 to 0.77; 5 studies; 375 participants), improve symptoms (SMD 0.37, 95% CI 0.09 to 0.65; 3 studies; 243 participants), and reduce medication usage (RR 5.35, 95% CI 1.29 to 22.11; 2 studies) in people with asthma. The MD for AQLQ score exceeded the minimal clinically important difference (MCID) of 0.5, but whether the mean changes exceeded the MCID for asthma symptoms is uncertain due to the lack of an established MCID in the severity scores used in the included studies. The effects of yoga on change from baseline forced expiratory volume in one second (MD 0.04 litres, 95% CI -0.10 to 0.19; 7 studies; 340 participants; I(2) = 68%) were not statistically significant. Two studies indicated improved asthma control, but due to very significant heterogeneity (I(2) = 98%) we did not pool data. No serious adverse events associated with yoga were reported, but the data on this outcome was limited. AUTHORS' CONCLUSIONS: We found moderate-quality evidence that yoga probably leads to small improvements in quality of life and symptoms in people with asthma. There is more uncertainty about potential adverse effects of yoga and its impact on lung function and medication usage. RCTs with a large sample size and high methodological and reporting quality are needed to confirm the effects of yoga for asthma.

Interleukin-2 as maintenance therapy for children and adults with acute myeloid leukaemia in first complete remission.

BACKGROUND: Acute myeloid leukaemia (AML) is a malignant cancer of hematopoietic stem cells. The treatment of AML consists of two treatment phases: the remission induction phase to achieve a rapid, complete remission (CR) and the consolidation phase to achieve a durable molecular remission. People in CR are at risk of AML relapse, and people with relapsed AML have poor survival prospects. Thus, there is a continuous need for treatments to further improve prognosis. Interleukin-2 (IL-2), an immune-stimulatory cytokine, is an alternative to standard treatment for people with AML to maintain the efficacy after consolidation therapy. Maintenance therapy is not an integral part of the standard treatment for AML. Studies have been conducted to evaluate the efficacy of IL-2 as maintenance therapy for people with AML in first CR, but the effect of IL-2 is not yet fully established. OBJECTIVES: To evaluate the efficacy and safety of IL-2 as maintenance therapy for children and adults with AML who have achieved first CR and have not relapsed. SEARCH METHODS: We systematically searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 8), MEDLINE (1950 to August 2015), EMBASE (1950 to August 2015), LILACS (1982 to August 2015), CBM (1978 to August 2015), relevant conference proceedings (2000 to 2015), and metaRegister of Controlled Trials (since inception to August 2015) of ongoing and unpublished trials. In addition, we screened the reference lists of relevant trials and reviews. SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCTs) comparing IL-2 with no treatment in people with AML who had achieved first CR and had not relapsed. We did not identify studies comparing IL-2 versus best supportive care or maintenance chemotherapy or studies comparing IL-2 plus maintenance chemotherapy versus maintenance chemotherapy alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies, extracted data with a predefined extraction form, and assessed risk of bias of included studies. We extracted data on the following outcomes: disease-free survival, overall survival, event-free survival, treatment-related mortality, adverse events, and quality of life. We measured the treatment effect on time-to-event outcomes and dichotomous outcomes with hazard ratio (HR) and risk ratio, respectively. We used inverse-variance method to combine HRs with fixed-effect model unless there was significant between-study heterogeneity. MAIN RESULTS: We included nine RCTs with a total of 1665 participants, comparing IL-2 with no treatment. Six studies included adult participants, and three studies included both adults and children. However, the latter three studies did not report data for children, thus we were unable to conduct subgroup analysis of children. One Chinese study did not report any outcomes of interest for this review. We included six trials involving 1426 participants in the meta-analysis on disease-free survival, and included five trials involving 1355 participants in the meta-analysis on overall survival. There is no evidence for difference between IL-2 group and no-treatment group regarding disease-free survival (HR 0.95; 95% CI 0.86 to 1.06, P = 0.37; quality of evidence: low) or overall survival (HR 1.05; 95% CI 0.95 to 1.16, P = 0.35; quality of evidence: moderate). Based on one trial of 161 participants, IL-2 exerted no effect on event-free survival (HR 1.02; 95% CI 0.79 to 1.32, P = 0.88; quality of evidence: low). Adverse events (including thrombocytopenia, neutropenia, malaise/fatigue, and infection/fever) were more frequent in participants receiving IL-2, according to one trial of 308 participants. No mortality due to adverse events was reported. None of the included studies reported treatment-related mortality or quality of life. AUTHORS' CONCLUSIONS: There is no evidence for a difference between IL-2 maintenance therapy and no treatment with respect to disease-free survival or overall survival of people with AML in first CR; however, the quality of the evidence is moderate or low, and further research is likely or very likely to have an important impact on the estimate or our confidence in the estimate. Adverse events seem to be more frequent in participants treated with IL-2, but the quality of the evidence is very low and our confidence in the estimates is very uncertain. Thus, further prospective randomised trials are needed before definitive conclusions can be drawn on these issues.

Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI) is a standard treatment for coronary heart disease (CHD). Restenosis, defined as a 50% reduction in luminal diameter at six months after PCI, indicates a need for revascularisation. Restenosis has proven to be a major drawback to PCI. Tong-xin-luo is one of the prophylactic strategies for cardiovascular events in patients after PCI that is widely used in China, but its efficacy and safety have not been systematically evaluated. OBJECTIVES: To systematically assess the efficacy and safety of Tong-xin-luo capsules in preventing cardiovascular events after PCI in patients with CHD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE (OVID), EMBASE (OVID), WanFang, Chinese Biomedical Database, Chinese Medical Current Contents, and China National Knowledge Infrastructure from their inception to June 2014. We also searched other resources, including ongoing trials and research registries. We applied no language restrictions. SELECTION CRITERIA: Randomised controlled trials of participants with CHD after PCI were included. Participants in the intervention group received Tong-xin-luo capsules for at least three months. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias. Any disagreements were resolved by discussion with a third review author. The primary outcomes included occurrence of angiographic restenosis and adverse events; the secondary outcomes included myocardial infarction, heart failure, angina, all cause mortality, mortality due to any cardiovascular event, use of revascularisation, patient acceptability, quality of life and cost-effectiveness. Dichotomous data were measured with risk ratios (RRs) with 95% confidence intervals (CIs). MAIN RESULTS: Sixteen studies involving 1063 participants were identified. The risk of bias for fifteen studies was high and along with imprecision and possible publication bias, this lowered our confidence in the results. There was low quality evidence that Tong-xi-luo reduced the rates of angiographic restenosis (RR 0.16, 95% CI 0.07 to 0.34), myocardial infarction (RR 0.32, 95% CI 0.16 to 0.66), heart failure (RR 0.26, 95% CI 0.11 to 0.62), and use of revascularisation (RR 0.26, 95% CI 0.15 to 0.45). There was very low quality evidence for the effect of Tong-xin-luo on all-cause mortality (RR 0.38, 95% CI 0.06 to 2.56), angina (RR 0.24, 95% CI 0.17 to 0.34) and death due to any cardiovascular event (RR 0.31, 95% CI 0.08 to 1.12). Adverse events were seldom reported, and included gastrointestinal reactions and nausea. AUTHORS' CONCLUSIONS: The addition of Tong-xin-luo to conventional Western medicine may possibly prevent restenosis and recurrence of cardiovascular events in patients with CHD after PCI. However, the data are limited by publication bias and high risk of bias for included studies. Further high-quality trials are required to evaluate the potential effects of this intervention.

Chemotherapy with cetuximab versus chemotherapy alone for chemotherapy-naive advanced non-small cell lung cancer.

BACKGROUND: In advanced non-small cell lung cancer (NSCLC), the effectiveness of standard cytotoxic chemotherapy seems to have reached a 'plateau', and there is a continuous need for new treatments to further improve the prognosis. Cetuximab is a monoclonal antibody targeted at the epidermal growth factor receptor (EGFR) signalling pathway. Basically, it is designed to inhibit the growth and metastasis among other biological processes of cancer. In combination with chemotherapy, it has been evaluated as a first-line treatment for advanced NSCLC in some randomised controlled trials (RCTs), with inconsistent results. OBJECTIVES: To evaluate the efficacy and toxicity of chemotherapy plus cetuximab, compared with chemotherapy alone, for advanced non-small cell lung cancer (NSCLC) previously untreated with chemotherapy or epidermal growth factor receptor (EGFR)-targeted drugs. SEARCH METHODS: We systematically searched the Cochrane Lung Cancer Review Group's Specialized Register (from inception to 17 December 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 12), MEDLINE (accessed through PubMed, 1966 to 17 December 2013), EMBASE (1980 to 17 December 2013), ClinicalTrials.gov (from inception to 17 December 2013), and the World Health Organization (WHO) International Clinical Trials Registry Platform (from inception to 17 December 2013). We also handsearched the proceedings related to lung cancer from the American Society of Clinical Oncology and European Society of Medical Oncology (2000 to 17 December 2013). We checked the reference lists of all eligible primary studies and review articles for additional potentially eligible studies. SELECTION CRITERIA: Eligible studies were RCTs that compared chemotherapy plus cetuximab with the same chemotherapy alone, in advanced NSCLC, previously untreated with chemotherapy or EGFR-targeted drugs, and measured at least one of the following: overall survival, progression-free survival, one-year survival rate, objective response rate, quality of life, or serious adverse events. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. We extracted the following data from each study: publication details, participant characteristics, regimens for intervention and control arms, outcome measures and effect size, and information related to the methodological quality of the study. We measured the treatment effects on dichotomous and time-to-event outcomes by risk ratio (RR) and hazard ratio (HR), with 95% confidence intervals (CIs), respectively. We conducted meta-analyses with Review Manager 5 using the random-effects model. We employed the Mantel-Haenszel method to combine RRs and the inverse-variance method to combine HRs. MAIN RESULTS: We included four trials, containing 2018 patients. The subjects were mostly white people (female: 26% to 56%), with a median age of 58 to 66 years. About half of them had histologically proven adenocarcinoma. Of the 2018 patients, 83% to 99% had their status measured using the Eastern Cooperative Oncology Group performance status, and had a score of 0 to 1 (which is usually considered as physically "fit").All four studies provided data on overall survival, progression-free survival, one-year survival rate, objective response rate, and serious adverse events, with two studies (1901 patients) investigating the effect of cetuximab on quality of life as well. The risk of bias was low for the data on overall survival and one-year survival rate, and high for the data on all other outcomes, mainly due to lack of blinding. Compared with chemotherapy alone, chemotherapy plus cetuximab improved overall survival (10.5 months versus 8.9 months; HR 0.87, 95% CI 0.79 to 0.96), one-year survival rate (45% versus 40%; RR 1.13, 95% CI 1.02 to 1.25), and objective response rate (30% versus 23%; RR 1.31, 95% CI 1.14 to 1.51). The difference in progression-free survival was at the limit of the statistical significance (4.9 months versus 4.4 months; HR 0.91, 95% CI 0.83 to 1.00). No significant difference in quality of life between the two treatment arms was reported by the two relevant studies. Patients in the cetuximab group experienced more acneiform rash (11.2% versus 0.3%; RR 37.36, 95% CI 10.66 to 130.95), hypomagnesemia (5.3% versus 0.8%; RR 6.57, 95% CI 1.13 to 38.12), infusion reaction (3.9% versus 1.1%; RR 3.50, 95% CI 1.76 to 6.94), diarrhoea (4.8% versus 2.3%; RR 2.10, 95% CI 1.26 to 3.48), hypokalaemia (6.3% versus 3.6%; RR 1.74, 95% CI 1.02 to 2.99), febrile neutropenia (10.6% versus 7.6%; RR 1.40, 95% CI 1.10 to 1.77), and leukopenia (58.1% versus 42.7%; RR 1.36, 95% CI 1.17 to 1.58) than did those in the control group. The difference in other adverse events did not reach statistical significance. According to the reports of original studies, the adverse events were generally manageable. There were no cetuximab-related deaths.The quality of the evidence is high for overall survival and one-year survival rate, but low for most secondary outcomes. AUTHORS' CONCLUSIONS: The combination of chemotherapy plus cetuximab is better than chemotherapy alone as the first-line treatment of advanced NSCLC in improving overall survival, while inducing higher rates of some reportedly manageable adverse events.

An internet-based epidemiological investigation of the outbreak of H7N9 Avian influenza A in China since early 2013.

BACKGROUND: In early 2013, a new type of avian influenza, H7N9, emerged in China. It quickly became an issue of great public concern and a widely discussed topic on the Internet. A considerable volume of relevant information was made publicly available on the Internet through various sources. OBJECTIVE: This study aimed to describe the outbreak of H7N9 in China based on data openly available on the Internet and to validate our investigation by comparing our findings with a well-conducted conventional field epidemiologic study. METHODS: We searched publicly accessible Internet data on the H7N9 outbreak primarily from government and major mass media websites in China up to February 10, 2014. Two researchers independently extracted, compared, and confirmed the information of each confirmed H7N9 case using a self-designed data extraction form. We summarized the epidemiological and clinical characteristics of confirmed H7N9 cases and compared them with those from the field study. RESULTS: According to our data updated until February 10, 2014, 334 confirmed H7N9 cases were identified. The median age was 58 years and 67.0% (219/327) were males. Cases were reported in 15 regions in China. Five family clusters were found. Of the 16.8% (56/334) of the cases with relevant data, 69.6% (39/56) reported a history of exposure to animals. Of the 1751 persons with a close contact with a confirmed case, 0.6% (11/1751) of them developed respiratory symptoms during the 7-day surveillance period. In the 97.9% (327/334) of the cases with relevant data, 21.7% (71/327) died, 20.8% (68/327) were discharged from a hospital, and 57.5% (188/327) were of uncertain status. We compared our findings before February 10, 2014 and those before December 1, 2013 with those from the conventional field study, which had the latter cutoff date of ours in data collection. Our study showed most epidemiological and clinical characteristics were similar to those in the field study, except for case fatality (71/327, 21.7% for our data before February 10; 45/138, 32.6% for our data before December 1; 47/139, 33.8% for the field study), time from illness onset to first medical care (4 days, 3 days, and 1 day), and time from illness onset to death (16.5 days, 17 days, and 21 days). CONCLUSIONS: Findings from our Internet-based investigation were similar to those from the conventional field study in most epidemiological and clinical aspects of the outbreak. Importantly, publicly available Internet data are open to any interested researchers and can thus greatly facilitate the investigation and control of such outbreaks. With improved efforts for Internet data provision, Internet-based investigation has a great potential to become a quick, economical, novel approach to investigating sudden issues of great public concern that involve a relatively small number of cases like this H7N9 outbreak.

Life satisfaction components and all-cause and cause-specific mortality: A large prospective cohort study.

BACKGROUND: Which life satisfaction components could be a target of positive psychological interventions for longevity is largely unknown. We aimed to investigate association of the composite measure of life satisfaction and its individual components with mortality. METHODS: This cohort study included UK Biobank participants who responded to questions concerning five components of life satisfaction at baseline. We generated a composite score representing overall life satisfaction, ranging from 0 (lowest) to 5 (highest). The outcomes were all-cause and cause-specific mortality. We used multivariable Cox regression to estimate hazard ratios (HR) for the associations of interest. RESULTS: Among 165,842 eligible participants, 12,261 all-cause deaths were observed over a median of 12.9-year follow-up. Overall life satisfaction was inversely associated with all-cause mortality (adjusted HR 0.94 [95% CI: 0.93-0.95] per 1 score increment). Health satisfaction showed the strongest association with all-cause mortality, with a fully adjusted HR of 0.52 (95% CI: 0.49-0.55) for high/extreme satisfaction and 0.63 (95% CI: 0.59-0.66) for moderate satisfaction, compared with unsatisfaction (P-trend<0.001), independent of other satisfaction components, regardless of physical health and sociodemographics. The association for family, friendship, work and financial satisfaction was attenuated when adjusted for other life satisfaction components. Similar findings were observed for cause-specific mortality. LIMITATIONS: Observational study with single baseline measurement of life satisfaction precludes the ability to establish causal relationship. CONCLUSIONS: Higher overall life satisfaction was associated with lower mortality. As the major contributor to lower mortality regardless of physical health and sociodemographics, health satisfaction could be an important target of positive psychological interventions for longevity.

A landscape of methodology and implementation of adaptive designs in cancer clinical trials.

BACKGROUND: The use of adaptive designs in cancer trials has considerably increased worldwide in recent years, along with the release of various guidelines for their application. This systematic review aims to comprehensively summarize the key methodological and executive features of adaptive designs in cancer clinical trials. METHODS: A comprehensive search from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials was conducted to screen eligible clinical trials that employed adaptive designs and were conducted in cancer patients. The methodological and executive characteristics of adaptive designs were the main measurements extracted. Descriptive analyses, primarily consisting of frequency and percentage, were employed to analyzed and reported the data. RESULTS: A total of 180 cancer clinical trials with adaptive designs were identified. The first three most common type of adaptive design was the group sequential design (n=114, 63.3 %), adaptive dose-finding design (n=22, 12.2 %), and adaptive platform design (n=16, 8.9 %). The results showed that 4.4 % (n=8) of trials conducted post hoc modifications, and around 29.4 % (n=53) did not provide the methods for controlling type I errors. Among phase II or above trials, 79.9 % (112/140) applied the surrogate endpoint as the primary outcome in these trials. Importantly, 27.2 % (49/180) of trials did not report clear information on the independent data monitoring committee (iDMC), and 13.3 % (n=24) without clear information on interim analyses. Interim analyses suggested 34.4 % (62/180) of trials being stopped for futility, 10.6 % (n=19) for efficacy, and 2.2 % (n=4) for safety concerns in the early stage. CONCLUSIONS: This study emphasizes adaptive designs in cancer trials face significant challenges in their design or strict implementation according to protocol, which might significantly compromise the validity and integrity of trials. It is thus important for researchers, sponsors, and policymakers to actively oversee and guide their application.

Specific convulsions and brain damage in children hospitalized for Omicron BA.5 infection: an observational study using two cohorts.

BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.

Promising biomarkers for predicting the outcomes of patients with KRAS wild-type metastatic colorectal cancer treated with anti-epidermal growth factor receptor monoclonal antibodies: a systematic review with meta-analysis.

KRAS mutations have been established as a major predictive biomarker for resistance to the treatment of metastatic colorectal cancer (mCRC) with anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR MoAbs). However, many patients with KRAS wild-type tumors still do not respond to the treatment. We conducted a systematic review with meta-analysis to assess whether BRAF mutations, PIK3CA mutations and PTEN loss can predict the outcomes of patients with KRAS wild-type mCRC treated with anti-EGFR MoAbs. Studies that explored the association of one or more of the three biomarkers with progression-free survival (PFS), overall survival (OS) and/or objective response rate (ORR) were identified through August 2012. Summary hazard ratios (HRs) and rate differences (RDs) and corresponding 95% confidence intervals (CIs) were calculated by using the random-effects model. BRAF mutations, PIK3CA exon 20 mutations and PTEN loss were all associated with shorter PFS (HR = 2.59, 95% CI 1.67-4.03; HR = 2.52, 95% CI 1.33-4.78 and HR = 1.75, 95% CI 1.19-2.56, respectively), shorter OS (HR = 2.74, 95% CI 1.79-4.19; HR = 3.29, 95% CI 1.60-6.75 and HR = 1.85, 95% CI 1.30-2.64, respectively) and lower ORR (RD = -36%, 95% CI -44 to -28%; RD = -38%, 95% CI -51 to -24% and RD = -41%, 95% CI -68 to -14%, respectively). PIK3CA exon 9 mutations were associated with none of the outcomes. Studies with relevant data consistently demonstrated a stronger predictive power of combined multiple biomarkers as compared to one alteration alone. These results suggest that BRAF mutations, PIK3CA exon 20 mutations and PTEN loss are predictive of worseoutcomes in KRAS wild-type mCRC treated with anti-EGFR MoAbs [corrected]. However, the quality of included studies varied, and some of the meta-analyses were limited by significant between-study heterogeneity. In the future, well-designed large randomized controlled trials conducted in KRAS wild-type mCRC patients with subgroup analysis according to BRAF, PIK3CA exon 20 and PTEN status are essential to fully assess the clinical relevance of these biomarkers.

KRAS p.G13D mutation and codon 12 mutations are not created equal in predicting clinical outcomes of cetuximab in metastatic colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: The authors conducted a systematic review and meta-analysis to examine whether patients who had metastatic colorectal cancer (mCRC) with the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G13D mutation (an amino acid substitution at position 13 in KRAS from a glycine to an aspartic acid) and received cetuximab treatment had better clinical outcomes than patients who had mCRC tumors with KRAS codon 12 mutations. METHODS: Relevant studies were identified by a search of MEDLINE, EMBASE, the Chinese Biomedical Database, and Wan Fang Digital Journals from inception to October 2011. The primary clinical outcomes included the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The pooled relative risk (RR) or hazard ratio (HR) was estimated by using fixed-effects or random-effects models according to heterogeneity between studies. RESULTS: Ten studies were considered eligible that included 1487 patients with mCRC. Patients who had tumors with the KRAS p.G13D mutation had a significantly higher ORR (10 studies; RR, 1.642; 95% confidence interval [CI], 1.131-2.384), longer PFS (1 study; HR, 0.54; 95% CI, 0.36-0.81), and longer OS (1 study; HR, 0.52; 95% CI, 0.33-0.80) than patients who had tumors with KRAS codon 12 mutations. Compared with patients who had KRAS wild-type tumors, patients with the p.G13D mutation had a significantly lower ORR (9 studies; RR, 0.540; 95% CI, 0.381-0.765) and nonsignificantly shorter PFS (1 study; HR, 0.99; 95% CI, 0.68-1.45) and OS (1 study; HR, 1.01; 95% CI, 0.66-1.54). CONCLUSIONS: Patients who had mCRC with the KRAS p.G13D mutation appeared to benefit more from cetuximab than patients who had tumors with KRAS codon 12 mutations. However, because of the limited sample sizes in the current meta-analysis, these results should be interpreted with caution.

Patients' experiences in different models of community health centers in southern China.

PURPOSE: Current health care reforms in China have an overall goal of strengthening primary care through the establishment and expansion of primary care networks based on community health centers (CHCs). Implementation in urban areas has led to the emergence of different models of ownership and management. The objective of this study was to evaluate the primary care experiences of patients in the Pearl River Delta as measured by the Primary Care Assessment Tool (PCAT) and the relationships with ownership and management in the 3 different models we describe. METHODS: This cross-sectional study was conducted on-site at CHCs in 3 cities within the Pearl River Delta, China, using a multistage cluster sampling method. A validated Mandarin Chinese version of the PCAT-Adult Edition (short version) was adopted to collect information from adult patients regarding their experiences with primary care sources. PCAT scores for individual primary care attributes and total primary care assessment scores were assessed with respect to sociodemographic characteristics, health characteristics, and health care service utilization across 3 primary care models. RESULTS: One thousand four hundred forty (1,440) primary care patients responded to the survey, for an overall response rate of 86.1%. Respondents gave government-owned and -managed CHCs the highest overall PCAT scores when compared with CHCs either managed by hospitals (95.18 vs 90.81; P = .005) or owned by private and social entities (95.18 vs 90.69; P =.007) as a result of better first-contact care (better first-contact utilization) and coordination of care (better service coordination and information system). Factors that were positively and significantly associated with higher overall assessment scores included the presence of a chronic condition (P <.001), having medical insurance (P = .006), and a self-reported good health status (P <.001). CONCLUSIONS: This study suggests that government-owned and -managed CHCs may be able to provide better first-contact care in terms of utilization and coordination of care, and may be better at solving the problem of underutilization of the CHCs as the first-contact point of care, one key problem facing the reforms in China.

Regular Glucosamine Use May Have Different Roles in the Risk of Site-Specific Cancers: Findings from a Large Prospective Cohort.

BACKGROUND: Previous studies indicated that glucosamine supplements may have a general anticancer effect. This study aimed to assess whether the potential effect differs across different types of cancers in a large prospective cohort study. METHODS: All participants from the UK Biobank who were free of cancers and had complete information on glucosamine use at baseline were included and followed up from 2006 until 2021. Cox proportional hazards models were used to assess the associations between regular glucosamine use and different site-specific cancers. Subgroup analyses were performed to explore potential interactions. Several sensitivity analyses were conducted to assess the robustness of the main findings. RESULTS: A total of 450,207 eligible participants (mean age: 56.2 years; females: 53.3%) were included, of whom 84,895 (18.9%) reported regular glucosamine use at baseline. During a median of 12.5 years follow-up, glucosamine use was significantly associated with an increased risk of overall cancer [HR, 1.04; 95% confidence interval (CI), 1.01-1.06], skin cancer (HR, 1.11; 95% CI, 1.07-1.15), and prostate cancer (HR, 1.07; 95% CI, 1.01-1.13), and with a reduced risk of lung cancer (HR, 0.88; 95% CI, 0.79-0.97) after adjusting for potential confounders. Statistical interaction was observed for gender, age, and education for the association of glucosamine use with overall cancer risk (all Pinteraction < 0.027). These results remained unchanged in the sensitivity analyses. CONCLUSIONS: Regular glucosamine use was associated with lower risk of lung cancer but higher risk of skin cancer, prostate cancer, and overall cancer. IMPACT: The roles of glucosamine use potentially differ in the development of different site-specific cancers.

Efficacy of SARS-CoV-2 vaccines and the dose-response relationship with three major antibodies: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The efficacy of SARS-CoV-2 vaccines in preventing severe COVID-19 illness and death is uncertain due to the rarity of data in individual trials. How well the antibody concentrations can predict the efficacy is also uncertain. We aimed to assess the efficacy of these vaccines in preventing SARS-CoV-2 infections of different severities and the dose-response relationship between the antibody concentrations and efficacy. METHODS: We did a systematic review and meta-analysis of randomised controlled trials (RCTs). We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, WHO, bioRxiv, and medRxiv for papers published between Jan 1, 2020 and Sep 12, 2022. RCTs on the efficacy of SARS-CoV-2 vaccines were eligible. Risk of bias was assessed using the Cochrane tool. A frequentist, random-effects model was used to combine efficacy for common outcomes (ie, symptomatic and asymptomatic infections) and a Bayesian random-effects model was used for rare outcomes (ie, hospital admission, severe infection, and death). Potential sources of heterogeneity were investigated. The dose-response relationships of neutralising, spike-specific IgG and receptor binding domain-specific IgG antibody titres with efficacy in preventing SARS-CoV-2 symptomatic and severe infections were examined by meta-regression. This systematic review is registered with PROSPERO, CRD42021287238. FINDINGS: 28 RCTs (n=286 915 in vaccination groups and n=233 236 in placebo groups; median follow-up 1-6 months after last vaccination) across 32 publications were included in this review. The combined efficacy of full vaccination was 44·5% (95% CI 27·8-57·4) for preventing asymptomatic infections, 76·5% (69·8-81·7) for preventing symptomatic infections, 95·4% (95% credible interval 88·0-98·7) for preventing hospitalisation, 90·8% (85·5-95·1) for preventing severe infection, and 85·8% (68·7-94·6) for preventing death. There was heterogeneity in the efficacy of SARS-CoV-2 vaccines against asymptomatic and symptomatic infections but insufficient evidence to suggest whether the efficacy could differ according to the type of vaccine, age of the vaccinated individual, and between-dose interval (p>0·05 for all). Vaccine efficacy against symptomatic infection waned over time after full vaccination, with an average decrease of 13·6% (95% CI 5·5-22·3; p=0·0007) per month but can be enhanced by a booster. We found a significant non-linear relationship between each type of antibody and efficacy against symptomatic and severe infections (p<0·0001 for all), but there remained considerable heterogeneity in the efficacy, which cannot be explained by antibody concentrations. The risk of bias was low in most studies. INTERPRETATION: The efficacy of SARS-CoV-2 vaccines is higher for preventing severe infection and death than for preventing milder infection. Vaccine efficacy wanes over time but can be enhanced by a booster. Higher antibody titres are associated with higher estimates of efficacy but precise predictions are difficult due to large unexplained heterogeneity. These findings provide an important knowledge base for interpretation and application of future studies on these issues. FUNDING: Shenzhen Science and Technology Programs.

Association between ATM 5557G>A polymorphism and breast cancer risk: a meta-analysis.

Epidemiological studies have evaluated the association between ATM 5557G>A (p.D1853N) polymorphism and breast cancer risk. However, the results remain conflicting rather than conclusive. To derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of PubMed and Medline databases were performed. A total of nine studies included 3155 cases and 2752 controls were identified. When all nine studies were pooled into the meta-analysis, there was no evidence for significant association between 5557G>A mutation and breast cancer risk(for G/A vs. G/G: OR = 1.05, 95% CI = 0.83-1.34; for A/A vs. G/G: OR = 0.77, 95% CI = 0.58-1.03; for dominant model: OR = 1.04, 95% CI = 0.82-1.31; for recessive model: OR = 0.87, 95% CI = 0.69-1.09). In the subgroup analyses by family history and ethnicity, significant associations were found among Amerindians (for G/A vs. G/G: OR = 2.19, 95% CI = 1.38-3.47; for dominant model: OR = 2.15, 95% CI = 1.37-3.38). In summary, the meta-analysis suggest that ATM 5557G>A polymorphism is associated with increased breast cancer risk among Amerindians. However, due to the small subjects included in analysis and the selection bias existed in some studies, the results for Amerindians should be interpreted with caution.

Interventions for preventing infection in nephrotic syndrome.

BACKGROUND: Infection is one of the most common complications and still remains a significant cause of morbidity and occasionally mortality in patients, especially children with nephrotic syndrome. Many different prophylactic interventions have been used or recommended for reducing the risks of infection in nephrotic syndrome in clinical practice. Whether the existing evidence is scientifically rigorous and which prophylactic intervention can be recommended for routine use based on the current evidence is still unknown. OBJECTIVES: To assess the benefits and harms of any prophylactic intervention for reducing the risk of infection in children and adults with nephrotic syndrome. SEARCH METHODS: We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL) (in The Cochrane Library), MEDLINE and Pre-MEDLINE (from 1966), EMBASE (from 1980), China Biological Medicine Database (1979 to December 2009), Chinese Science and Technique Journals Database (to December 2009), China National Infrastructure (to December 2009), WangFang database (to December 2009), reference lists of nephrology textbooks, review articles, relevant studies and abstracts from nephrology meetings without language restriction.Date of last search: 6 February 2012 SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing any prophylactic interventions (pharmacological or non-pharmacological) for preventing any infection in children and adults with nephrotic syndrome. DATA COLLECTION AND ANALYSIS: Two authors independently assessed and extracted information. Information was collected on methods, participants, interventions and outcomes (appearance of infection, mortality, quality of life and adverse events). Results were expressed as risk ratios (RR) for dichotomous outcomes or as mean differences (MD) for continuous data with 95% confidence intervals (CI). MAIN RESULTS: Twelve studies conducted in China, including 762 children with nephrotic syndrome were identified. No studies were identified in adults. All studies compared one kind of prophylactic pharmacotherapy (intravenous immunoglobulin (IVIG), thymosin, oral transfer factor, mannan peptide tablet, Bacillus Calmette-Guerin (BCG) vaccine injection, polyvalent bacterial vaccine (Lantigen B) and two kinds of Chinese medicinal herbs: a compound of Chinese medicinal herbs (TIAOJINING) and Huangqi (astragalus) granules) plus baseline treatment with baseline treatment alone. No RCTs were identified comparing antibiotics, non-pharmacological prophylaxis, or pneumococcal vaccination. Four studies showed a significantly beneficial effect of IVIG on preventing nosocomial or unspecified infection in children with nephrotic syndrome (RR 0.47, 95% CI 0.31 to 0.73). Thymosin (RR 0.50, 95% CI 0.26 to 0.97), oral transfer factor (RR 0.51, 95% CI 0.35 to 0.73), BCG vaccine injection (RR 0.68, 95% CI 0.48 to 0.95), Huangqi granules (RR 0.62, 95% CI 0.47 to 0.83) and TIAOJINING (RR 0.59, 95% CI 0.43 to 0.81) were also effective in reducing the risk of infection in children with nephrotic syndrome. However mannan peptide tablet (RR 0.46, 95% CI 0.21 to 1.01) and polyvalent bacterial vaccine (RR 0.24, 95% CI 0.06 to1.00) were not superior to baseline treatment in reducing the risk of infection for nephrotic children. No serious adverse events were reported. AUTHORS' CONCLUSIONS: IVIG, thymosin, oral transfer factor, BCG vaccine, Huangqi granules and TIAOJINING may have positive effects on the prevention of nosocomial or unspecified infection with no obvious serious adverse events in children with nephrotic syndrome. However the methodological quality of all studies was poor, the sample sizes small, and all studies were from China, and thus there is no strong evidence on the effectiveness of these interventions.

Toremifene versus tamoxifen for advanced breast cancer.

BACKGROUND: Toremifene (TOR) and tamoxifen (TAM) can both be used as treatments for advanced breast cancer. OBJECTIVES: To compare the efficacy and safety of TOR with TAM in patients with advanced breast cancer. SEARCH METHODS: The Cochrane Breast Cancer Group's Specialised Register was searched (1 July 2011) using the codes for "toremifene", "fareston", "tamoxifen, "nolvadex, and "breast cancer". We also searched MEDLINE (via PubMed) (from inception to 1 July 2011), EMBASE (via Ovid) (from inception to 1 July 2011), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2011), and the WHO International Clinical Trials Registry Platform search portal (1 July 2011). In addition, we screened the reference lists of relevant trials or reviews. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared the efficacy and safety, or both of TOR with TAM in women with advanced breast cancer. Trials that provided sufficient data on one of the following items: objective response rate (ORR), time to progression (TTP), overall survival (OS), and adverse events, were considered eligible for inclusion. DATA COLLECTION AND ANALYSIS: Studies were assessed for eligibility and quality. Two review authors independently extracted the following details: first author, publication year, country, years of follow-up, treatment arms, intention-to-treat (ITT) population size, menopausal status of patients, hormone receptor status, response criteria, efficacy and safety outcomes of TOR and TAM arms. Hazard ratios (HR) were derived for time-to-event outcomes, where possible, and response and adverse events were analysed as dichotomous variables. We used a fixed-effect model for meta-analysis unless there was significant between-study heterogeneity. MAIN RESULTS: A total of 2061 patients from seven RCTs were included for final analysis, with 1226 patients in the TOR group and 835 patients in the TAM group. The ORR for the TOR group was 25.8% (316/1226) whereas, the ORR for the TAM group was 26.9% (225/835). The pooled risk ratio (RR) suggested that the ORRs were not statistically different between the two groups (RR 1.02, 95% confidence interval (CI) 0.88 to 1.18, P = 0.83). The median TTP was 6.1 months for the TOR group and 5.8 months for the TAM group. The median OS was 27.8 months for the TOR group and 27.6 months for the TAM group. There were no significant differences in TTP and OS between the two therapeutic groups (for TTP: HR 1.08, 95% CI 0.94 to 1.24; for OS: HR 1.02, 95% CI 0.86 to 1.20). The frequencies of most adverse events were also similar in the two groups, while headache seemed to occur less in the TOR group than in the TAM group (RR 0.14, 95% CI 0.03 to 0.74, P = 0.02). There was no significant heterogeneity between studies in most of the above meta-analyses. Sensitivity analysis did not alter the results. AUTHORS' CONCLUSIONS: TOR and TAM are equally effective and the safety profile of the former is at least not worse than the latter in the first-line treatment of patients with advanced breast cancer. Thus, TOR may serve as a reasonable alternative to TAM when anti-oestrogens are applicable but TAM is not the preferred choice for some reason.