Outcome Indexes in Randomized Controlled Trials of Chinese Medicine for Diabetic Kidney Disease / 中国实验方剂学杂志

ObjectiveTo analyze the utilization of outcome indexes and other trial design elements in randomized controlled trials （RCTs） of Chinese medicine for diabetic kidney disease （DKD） and provide a basis for the design of clinical trials and the development of core outcome index sets for Chinese medicine treatment of DKD. MethodSeven medical databases （CNKI， Wanfang Data， VIP， SinoMed， etc.） and two clinical trial registration centers （clinicaltrials.gov and chinadrugtrials.org.cn） were searched for RCTs of Chinese medicine for DKD published in the past 5 years. The included studies were assessed for risk of bias using the Cochrane Handbook for Systematic Reviews of Interventions， and the outcome indexes and other trial design elements were statistically analyzed. ResultNinety-seven RCTs were enrolled， including five trial registration protocols. The overall risk of bias was found to be high in the included studies. Stage Ⅲ DKD （36 studies， 41.38%） and the Qi-Yin deficiency with blood stasis syndrome （16 studies， 26.23%） were the top DKD stage and traditional Chinese medicine （TCM） syndrome， respectively. The treatment duration ranged from 2 weeks to 96 weeks， with 12 weeks being the most common duration （52 studies， 56.52%）. A total of 152 outcome indexes were used in 92 RCTs and five registered trials， with a frequency of 1 040 times. These indexes were classified into eight categories： Laboratory tests （blood）， laboratory tests （urine）， clinical efficacy， TCM syndrome score， quality of life scales， vital signs， other indexes， and other events. The most frequently used outcome indexes were serum creatinine （68 times， 70.10%）， clinical response rate （55 times， 56.70%）， fasting blood glucose （51 times， 52.58%）， blood urea nitrogen （48 times， 49.48%）， total cholesterol （47 times， 48.45%）， and 24-hour urinary protein excretion （43 times， 44.33%）. Safety indexes were used in 56 RCTs and two registered trials， with 53 different indexes and a frequency of 227 times. The most frequently used safety indexes were adverse reactions （49 times， 84.48%）， liver function （28 times， 48.28%）， complete blood count （24 times， 41.38%）， electrocardiogram （17 times， 29.31%）， and urinalysis （14 times， 24.14%）. Ten RCTs and five registered trials reported primary outcome indexes， and 54 RCTs reported clinical response rates. ConclusionThe current design of outcome indexes in RCTs of Chinese medicine for DKD is not standardized. In the future， efforts should be made to develop core outcome index sets that highlight the characteristics of TCM， improve the quality of clinical research， and enhance the applicability of trial results.

[Study on key outcome indexes in treatment of migraine with acupuncture and moxibustion].

OBJECTIVE: To identify the key outcome indexes in treatment of migraine with acupuncture and moxibustion. METHODS: Using literature research, questionnaire survey and consensus conference, the key outcome indexes in treatment of migraine with acupuncture and moxibustion were screened and prioritized. RESULTS: The critical outcome indexes for the treatment in attack stage of migraine included 6 effectiveness outcome indexes (headache intensity, headache duration, headache relieve time, effectiveness and level of headache relief within 2 h, headache-related quality of life, level of headache relief within 24 h) and 1 safety outcome index (incidence of serious adverse reactions). The critical outcome indexes for prophylactic treatment included 6 effectiveness outcome indexes (headache day, headache frequency, headache intensity, effective rate, headache-related quality of life, health-related quality of life) and 1 safety outcome index (incidence of serious adverse reactions). CONCLUSION: In terms of the attack stage treatment and prophylactic treatment with acupuncture and moxibustion, the outcome indexes are different, among which, those can directly reflect the conditions of migraine should be optioned in priority. To assess the effectiveness of attack stage, the headache intensity is preferred, using the visual analogue scale (VAS) score, and the preferred time is 2 hours after treatment. Regarding the effectiveness of prophylactic treatment, the headache day, headache frequency and headache intensity should be firstly considered in the assessment, in which, the preferred time for assessment is 12 weeks into treatment, while, the best time for follow-up should be 12 weeks after treatment completion. When the quality of life is considered, the migraine-specific quality of life questionnaire (MSQ) is the top option. For either the attack stage treatment or the prophylactic treatment, the high attention should be laid on the outcome indexes for safety and medical economics evaluation.

Balancing the Extent of Resection and Ischemic Complications in Insular Glioma Surgery: Technical Nuances and Proposal of a Novel Composite Postoperative Outcome Index.

Background: Maximal safe resection remains the most desired goal of insular glioma surgery. Intraoperative surgical adjuncts provide better tumor visualization and real-time "safety" data but remain limited due to a high cost and limited availability. Objective: To highlight the importance of anatomical landmarks in insular glioma resection and avoidance of vascular complications. We also propose to objectify the onco-functional balance in insular glioma surgery. Methods: Forty-six insular gliomas operated upon by a single surgeon between January 2015 and February 2020 were reviewed, focusing on the operative technique and clinical outcomes. A novel composite postoperative outcome index (CPOI) was designed, comprising the extent of resection and permanent postoperative deficits, and utilized to assess the surgical outcomes. Results: Gross-total, near-total, and subtotal resections were achieved in 10.9%, 52.1% (n = 24), and 36.9% (n = 17) patients, respectively. The median overall survival (OS) was 20 months (95% CI = 9.56-30.43). CPOI was optimal in 38 patients (82.6%). A well-defined tumor margin (P = 0.01) and surgeon's experience (P = 0.04) were significantly associated with an optimal CPOI. Out of seven (15.2%) patients who developed permanent neurological deficits, three (6.5%) patients had severe disability. Favorable prognostic factors of survival included younger age (<40 years) (P = 0.002), tumors with only frontal lobe extension (P = 0.011), tumors with caudate head involvement (P = 0.04), and non-glioblastoma histology (P = 0.006). Conclusion: Tumor margin and increasing surgeon experience are critical to an optimal postoperative outcome. Respecting the basi-sulcal plane is key to lenticulostriate artery preservation. Caudate head involvement is a new favorable prognostic factor in insular gliomas.

Effects of Early Palliative Care in Advanced Cancer Patients: A Meta-Analysis.

Objective: Advanced cancer patients often suffer from a reduced quality of life (QoL) and cancer-related symptoms. Early palliative care may improve their QoL and symptom severity. Methods: We conducted a meta-analysis of the effects of early palliative care on QoL, symptom severity, and other outcomes in advanced cancer patients, and searched PubMed, Embase, CINAHL, MEDLINE, and the Cochrane Library databases for potential randomized controlled trials (RCTs). The primary outcome was QoL. The secondary outcomes were symptom intensity and functional well-being (Trial Outcome Index, TOI). The study protocol has been registered and approved by PROSPERO (CRD42020164047). Results: We obtained 12 RCTs enrolling 2980 participants. Compared with the usual care, early palliative care significantly improved QoL at ≤ 3 months (SMD = .16, 95% CI = .05-.27) and when treated more 3 months (SMD = .26, 95% CI = .11-.40). Compared with usual treatment, patients who received early palliative care exhibited a significant reduction in symptom intensity when treated more than 3 months (SMD = .18, 95% CI = .06-.31) and in TOI ≤ 3 months (SMD = .28, 95% CI = .11-.45). Conclusions: Early palliative care improves QoL, symptom intensity, and TOI in advanced cancer patients. We recommend introducing early palliative care for advanced cancer patients as the approach provides additional clinical benefits compared with usual care.

[Analysis of outcome indexes in randomized controlled trials of traditional Chinese medicine for rheumatic heart disease].

The present study analyzed the efficacy evaluation indexes of the randomized controlled trials(RCTs) of Chinese medi-cine in the treatment of rheumatic heart disease to lay the foundation for the construction of the corresponding core outcome index set. Clinical RCTs with a definite diagnosis of rheumatic heart disease were retrieved from CNKI, Wanfang, VIP, Sino Med, Pub Med, EMbase, and Cochrane Library from January 1, 2010, to December 31, 2020. Thirty-five RCTs were included, involving 3 314 patients and 41 efficacy evaluation indexes, which covered seven domains [traditional Chinese medicine(TCM) symptoms/syndromes, symp-toms/signs, physical and chemical examination, quality of life, long-term prognosis, economic evaluation, and safety events]. Physi-cal and chemical examination(56. 91%) and symptoms/signs(29. 27%) were the more frequently applied. The number of indexes used in a single trial ranged from 1 to 15, with an average of 4. The measurement time points of the top five indexes in the frequency of use were as follows: total response rate was reported at five measurement time points, ranging from 14 days to 6 months; left ventri-cular ejection fraction was measured at eight time points ranging from 5 days to 6 months; left ventricular end systolic diameter was measured at six time points, ranging from 5 days to 6 months; interleukin-2(IL-2) and tumor necrosis factor-α(TNF-α) were repor-ted 28 days after treatment. At present, there are many problems in the efficacy outcome indexes of RCTs in the treatment of rheumatic heart disease with TCM, such as large difference in quantity, unclear primary and secondary indexes, unreasonable selection of " surro-gate indexes", insufficient attention to long-term prognostic indexes and safety event indexes, non-standard application of composite in-dexes, long measurement period, and lack of TCM characteristics. It is urgent to establish the core outcome set for TCM treatment of rheumatic heart disease.

Analysis of outcome indexes in randomized controlled trials of traditional Chinese medicine for rheumatic heart disease / 中国中药杂志

The present study analyzed the efficacy evaluation indexes of the randomized controlled trials(RCTs) of Chinese medi-cine in the treatment of rheumatic heart disease to lay the foundation for the construction of the corresponding core outcome index set. Clinical RCTs with a definite diagnosis of rheumatic heart disease were retrieved from CNKI, Wanfang, VIP, Sino Med, Pub Med, EMbase, and Cochrane Library from January 1, 2010, to December 31, 2020. Thirty-five RCTs were included, involving 3 314 patients and 41 efficacy evaluation indexes, which covered seven domains [traditional Chinese medicine(TCM) symptoms/syndromes, symp-toms/signs, physical and chemical examination, quality of life, long-term prognosis, economic evaluation, and safety events]. Physi-cal and chemical examination(56. 91%) and symptoms/signs(29. 27%) were the more frequently applied. The number of indexes used in a single trial ranged from 1 to 15, with an average of 4. The measurement time points of the top five indexes in the frequency of use were as follows: total response rate was reported at five measurement time points, ranging from 14 days to 6 months; left ventri-cular ejection fraction was measured at eight time points ranging from 5 days to 6 months; left ventricular end systolic diameter was measured at six time points, ranging from 5 days to 6 months; interleukin-2(IL-2) and tumor necrosis factor-α(TNF-α) were repor-ted 28 days after treatment. At present, there are many problems in the efficacy outcome indexes of RCTs in the treatment of rheumatic heart disease with TCM, such as large difference in quantity, unclear primary and secondary indexes, unreasonable selection of " surro-gate indexes", insufficient attention to long-term prognostic indexes and safety event indexes, non-standard application of composite in-dexes, long measurement period, and lack of TCM characteristics. It is urgent to establish the core outcome set for TCM treatment of rheumatic heart disease.

[Analysis of status quo of RCT outcome indexes in treatment of acute ischemic stroke with traditional Chinese medicine].

The purpose of this study was to evaluate the selection situation of outcome indexes in randomized controlled trials of traditional Chinese medicine(TCM) in the treatment of acute ischemic stroke and to provide suggestions for future research. In this study, four Chinese databases and three English databases were searched from January 2017 to June 2019. The randomized controlled trials of traditional Chinese medicine in the treatment of ischemic stroke were selected according to the pre-established selection criteria. Cochrane bias risk assessment tool was used to evaluate the quality of the included studies. A total of 20 651 related articles were searched, and 11 662 ones were left after eliminating the repetitions. Finally, 42 articles were included, including 36 articles in Chinese and 6 articles in English, 40 randomized controlled trials and 2 registration schemes of randomized controlled trials. The results showed that the outcome indexes of 42 randomized controlled trials were mainly divided into seven categories, that is clinical outcome index, blood biochemical index, mental state evaluation index, cerebral hemodynamics index, index of evaluating the degree of carotid artery stenosis, safety indicators and other indicators. The blood biochemical index was the one with highest frequency, followed by the clinical outcome index. TCM syndrome score was used as an indicator of curative outcome in 17 studies. After the analysis, it was found that there were many problems in selecting the outcome indexes for the randomized controlled trials of traditional Chinese medicine in the treatment of cerebral apoplexy. For example, the end point index and hard index were rarely selected as the main outcome indicators, and the vast majority of them were intermediate alternative indexes; recognized curative effect could not be obtained; there were too many kinds of outcome indicators and excessive heterogeneity, hindering the promotion of superior treatment measures of traditional Chinese medicine in clinical practice. Therefore, we should draw lessons from the establishment method of the international core index outcome index set, construct the core index outcome index set of traditional Chinese medicine in the treatment of ischemic stroke, and develop the outcome index set which accords with the curative effect characteristics of traditional Chinese medicine treatment mea-sures to solve the problems effectively.

Analysis of status quo of RCT outcome indexes in treatment of acute ischemic stroke with traditional Chinese medicine / 中国中药杂志

The purpose of this study was to evaluate the selection situation of outcome indexes in randomized controlled trials of traditional Chinese medicine(TCM) in the treatment of acute ischemic stroke and to provide suggestions for future research. In this study, four Chinese databases and three English databases were searched from January 2017 to June 2019. The randomized controlled trials of traditional Chinese medicine in the treatment of ischemic stroke were selected according to the pre-established selection criteria. Cochrane bias risk assessment tool was used to evaluate the quality of the included studies. A total of 20 651 related articles were searched, and 11 662 ones were left after eliminating the repetitions. Finally, 42 articles were included, including 36 articles in Chinese and 6 articles in English, 40 randomized controlled trials and 2 registration schemes of randomized controlled trials. The results showed that the outcome indexes of 42 randomized controlled trials were mainly divided into seven categories, that is clinical outcome index, blood biochemical index, mental state evaluation index, cerebral hemodynamics index, index of evaluating the degree of carotid artery stenosis, safety indicators and other indicators. The blood biochemical index was the one with highest frequency, followed by the clinical outcome index. TCM syndrome score was used as an indicator of curative outcome in 17 studies. After the analysis, it was found that there were many problems in selecting the outcome indexes for the randomized controlled trials of traditional Chinese medicine in the treatment of cerebral apoplexy. For example, the end point index and hard index were rarely selected as the main outcome indicators, and the vast majority of them were intermediate alternative indexes; recognized curative effect could not be obtained; there were too many kinds of outcome indicators and excessive heterogeneity, hindering the promotion of superior treatment measures of traditional Chinese medicine in clinical practice. Therefore, we should draw lessons from the establishment method of the international core index outcome index set, construct the core index outcome index set of traditional Chinese medicine in the treatment of ischemic stroke, and develop the outcome index set which accords with the curative effect characteristics of traditional Chinese medicine treatment mea-sures to solve the problems effectively.

Effect of a cluster randomised team training intervention on adverse perinatal and maternal outcomes: a stepped wedge study.

OBJECTIVE: To study the effect of an intervention based on Crew Resource Management team training, including a tool for structured communication, on adverse perinatal and maternal outcomes. DESIGN: Stepped wedge. SETTING: The Netherlands. POPULATION OR SAMPLE: Registry data of 8123 women referred from primary care to a hospital during childbirth, at ≥ 32.0 weeks of singleton gestation and with no congenital abnormalities, in the period 2012-15. METHODS: Obstetric teams of five hospitals and their surrounding primary-care midwifery practices participated in the intervention. In total, 49 team training sessions were organised for 465 care professionals (75.5% participated). Adverse perinatal and maternal outcomes before, during and after the intervention were analysed using multivariate logistic regression analyses. MAIN OUTCOME MEASURES: Adverse Outcome Index (AOI-5), a composite measure involving; intrapartum or neonatal death, admission to neonatal intensive care unit, Apgar < 7 at 5 minutes, postpartum haemorrhage and/or perineal tear. RESULTS: In total, an AOI-5 score was reported in 11.3% of the study population. No significant difference was found in the incidence of the AOI-5 score after the intervention compared with before the intervention (OR 1.07: 95% CI 0.92-1.24). CONCLUSIONS: We found no effect of the intervention on adverse perinatal and maternal outcomes for women who were referred during childbirth. Team training is appreciated in practice, but evidence on the long-term impact is still limited. Upcoming studies should build on previous research and consider more sensitive outcome measures. TWEETABLE ABSTRACT: A cluster randomised team training intervention showed no effect on adverse perinatal and maternal outcomes for women referred during childbirth.

Predictors of quality of life and survival following Gamma Knife surgery for lung cancer brain metastases: a prospective study.

OBJECTIVE Lung cancer (LC) patients who develop brain metastases (BMs) have a poor prognosis. Estimations of survival and risk of treatment-related deterioration in quality of life (QOL) are important when deciding on treatment. Although we know of several prognostic factors for LC patients with BMs, the role of QOL has not been established. Authors of this study set out to evaluate changes in QOL following Gamma Knife surgery (GKS) for BMs in LC patients and QOL as a prognostic factor for survival. METHODS Forty-four of 48 consecutive LC patients with BMs underwent GKS in the period from May 2010 to September 2011, and their QOL was prospectively assessed before and 1, 3, 6, 9, and 12 months after GKS by using the Functional Assessment of Cancer Therapy-Brain (FACT-BR) questionnaire. A mixed linear regression model was used to identify potential predictive factors for QOL and to assess the effect of GKS and the disease course on QOL at follow-up. RESULTS Mean QOL as measured by the brain cancer subscale (BRCS) of the FACT-BR remained stable from baseline (score 53.0) up to 12 months post-GKS (57.1; p = 0.624). The BRCS score improved for 32 patients (72.3%) with a total BM volume ≤ 5 cm3. Mean improvement in these patients was 0.45 points each month of follow-up, compared to a decline of 0.50 points each month despite GKS treatment in patients with BM volumes > 5 cm3 (p = 0.04). Asymptomatic BMs (p = 0.01), a lower recursive partitioning analysis (RPA) classification (p = 0.04), and a higher Karnofsky Performance Scale (KPS) score (p < 0.01) at baseline were predictors for a high, stable QOL after GKS. After multivariate analysis, a high KPS score (p < 0.01) remained the only positive predictor of a high, stable QOL post-GKS. Median survival post-GKS was 5.6 months (95% CI 1.0-10.3). A higher BRCS score (p = 0.01), higher KPS score (p = 0.01), female sex (p = 0.01), and the absence of liver (p = 0.02), adrenal (p = 0.02), and bone metastases (p = 0.03) predicted longer survival in unadjusted models. However, in multivariate analyses, a higher BRCS score (p < 0.01), female sex (p = 0.01), and the absence of bone metastases (p = 0.02) at GKS remained significant predictors. Finally, the BRCS score's predictive value for survival was compared with the values for the variables behind well-known prognostic indices: age, KPS score, extracranial disease status, and number and volume of BMs. Both BRCS score (p = 0.01) and BM volume (p = 0.05) remained significant predictors for survival in the final model. CONCLUSIONS Patient-reported QOL according to the BRCS is a predictor of survival in patients with BMs and may be helpful in deciding on the optimal treatment. Gamma Knife surgery is a safe and effective therapeutic modality that improves QOL for LC patients with a BM volume ≤ 5 cm3 at treatment. Careful follow-up and salvage therapy on demand seem to prevent worsening of QOL due to relapse of BMs.

Standardized Testing Practices: Effect on Graduation and NCLEX® Pass Rates.

The use standardized testing in pre-licensure nursing programs has been accompanied by conflicting reports of effective practices. The purpose of this project was to describe standardized testing practices in one states' nursing programs and discover if the use of a cut score or oversight of remediation had any effect on (a) first time NCLEX® pass rates, (b) on-time graduation (OTG) or (c) the combination of (a) and (b). Administrators of 38 nursing programs in one Southwest state were sent surveys; surveys were returned by 34 programs (89%). Survey responses were compared to each program's NCLEX pass rate and on-time graduation rate; t-tests were conducted for significant differences associated with a required minimum score (cut score) and oversight of remediation. There were no significant differences in NCLEX pass or on-time graduation rates related to establishment of a cut score. There was a significant difference when the NCLEX pass rate and on-time graduation rate were combined (Outcome Index "OI") with significantly higher program outcomes (P=.02.) for programs without cut-scores. There were no differences associated with faculty oversight of remediation. The results of this study do not support establishment of a cut-score when implementing a standardized testing.

Quality of life is maintained using Gamma Knife radiosurgery: a prospective study of a brain metastases patient cohort.

OBJECTIVE Gamma Knife radiosurgery (GKRS) is increasingly used in the management of brain metastases (BMs), but few studies have evaluated how GKRS impacts quality of life (QOL). The aim of this study was to monitor QOL as the primary end point following GKRS in a patient cohort with BM. METHODS The study included 97 consecutive patients with 1-6 BMs treated with GKRS between May 2010 and September 2011. QOL was assessed at baseline and at 1, 3, 6, 9, and 12 months postoperatively using the Functional Assessment of Cancer Therapy-Brain (FACT-BR) questionnaire with the brain cancer subscale (BRCS) questionnaire. Factors predicting QOL were identified by mixed linear regression analyses. Local control and toxicity were evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) and the European Organisation for Research and Treatment/Radiation Therapy Oncology Group (EORTC/RTOG) criteria of late effects, respectively. RESULTS Compliance was high from baseline (97%) to 12-month follow-up (78%). Mean BRCS scores remained high during follow-up: they improved in 66% of patients and remained unchanged in 6% at 9 months. Local control (p = 0.018), improved symptoms (p = 0.005), and stable extracerebral disease (p = 0.001) correlated with high QOL-BRCS score. High baseline recursive partitioning analysis class predicted improved QOL (p = 0.031), whereas high Karnofsky Performance Scale score (p = 0.017), asymptomatic BMs (p = 0.001), and no cognitive deficits (p = 0.033) or seizures (p = 0.040) predicted high, stable QOL-BRCS during the 12-month follow-up. CONCLUSIONS QOL remained stable for up to 12 months following GKRS for the total cohort. High QOL was reported if local control occurred, cerebral symptoms improved/stabilized, or the need for steroids declined, which all reflected successful GKRS. Conversely, low QOL accompanied progression of intra- and extracerebral disease. Based on the study findings, GKRS appears to be a safe and effective treatment option for patients with BMs.

Health-related quality of life of postmenopausal Chinese women with hormone receptor-positive early breast cancer during treatment with adjuvant aromatase inhibitors: a prospective, multicenter, non-interventional study.

BACKGROUND: Estimating quality of life (QoL) in patients with breast cancer is of importance in assessing treatment outcomes. Adjuvant endocrine therapy is widely used for hormone receptor-positive (HR+) early-stage breast cancer (EBC), and evidence suggests that aromatase inhibitors (AIs) may improve QoL for these patients. This study evaluated QoL in postmenopausal Chinese patients with HR+ EBC taking AIs. METHODS: This was a prospective, multicenter, and observational study that had no intent to intervene in the current treatment of recruited patients. Eligible patients were recruited within 7 days of beginning adjuvant treatment with AIs. The Functional Assessment of Cancer Therapy-Breast (FACT-B) scale was used to evaluate the patients' QoL. Data were collected at baseline and at 6, 12, 18, and 24 months. RESULTS: From June 2010 to October 2013, a total of 494 patients with HR+ EBC were recruited from 21 centers. There was a 7.51-point increase in the patients' mean FACT-B trial outcome index (TOI), from 90.69 at baseline to 98.72 at 24 months (P < .0001). The mean TOI scores at baseline, 6, 12, and 18 months were 90.69, 94.36, 97.71, and 96.75, respectively (P < .0001, for all). The mean (FACT-B) emotional well-being subscale scores at baseline, 6, 12, 18, and 24 months were 16.32, 16.55, 17.34 (P < .0001), 17.47 (P < .0001), and 17.85 (P < .0001), respectively, and social well-being scores were 18.61, 19.14 (P < .04), 19.35 (P < .008), 18.32, and 18.40, respectively. In the mixed model, baseline TOI, clinical visits, prior chemotherapies, age group, and axillary lymph-node dissection presented statistically significant effects on the change of FACT-B TOI and FACT-B SWB, whereas only baseline TOI, clinical visits, and prior chemotherapies presented statistically significant effects on the change of FACT-B EWB. FACT-B TOI, being the most pertinent and precise indicator of patient-reported QoL, demonstrated significant changes reflecting clinical benefit of adjuvant AIs endocrine therapy in the QoL of HR + EBC patients. CONCLUSIONS: The study demonstrated significant improvements in the long-term QoL of postmenopausal Chinese patients with HR+ EBC at 6, 12, 18, and 24 months after starting treatment with AIs. The current study indicates improved long-term QoL with AI adjuvant treatment, which will aid clinicians in optimizing treatment to yield effective healthcare outcomes. TRIAL REGISTRATION: Clinicaltrials.gov NCT01144572.

Feasibility of Implementing a Standardized Clinical Performance Indicator to Evaluate the Quality of Obstetrical Care in British Columbia.

OBJECTIVES: To establish the feasibility of implementing a previously-published clinical standardized performance indicator, the Adverse Outcome Index (AOI), using routinely-collected data in a population-based perinatal database and to examine variation in the indicator over time and between hospitals. METHODS: Maternal and newborn medical record data contained in the British Columbia Perinatal Data Registry, 2004-2013, were used to calculate an AOI (a composite of 10 maternal and newborn adverse events) and its severity-weighted scores, the Weighted Adverse Outcome Score and the Severity Index. Temporal trends in the indices were examined by plotting annual risks and weighted risks with 95% confidence intervals. Hospital-level risks were calculated with 95% confidence intervals, adjusting for patient case-mix. RESULTS: Among 410,054 singleton deliveries in British Columbia, the risk of AOI was 5.8 per 100, while the Weighted Adverse Outcome Score and Severity Index were 1.6 and 27.4, respectively. The risk of AOI did not change significantly over the study period, while the Severity Index decreased from 29.3 (95% CI 26.7-31.9) in 2004 to 23.9 (22.0-25.8) in 2013. Fifteen of 52 hospitals had risks of AOI significantly above the provincial median. The hospitals' risks of AOI were not correlated with their Severity Indices (r = 0.02). CONCLUSIONS: The AOI can successfully be estimated using data from a population-based database, and used to monitor trends in safety of labour and delivery over time and between hospitals. The low correlation between frequency and severity of adverse events confirms the importance of considering event severity in perinatal population health surveillance.

The association between the regular use of preventive labour induction and improved term birth outcomes: findings of a systematic review and meta-analysis.

BACKGROUND: Despite a lack of high-quality evidence, the use of 'non-indicated' term labour induction is increasingly restricted throughout the world. OBJECTIVES: To assess published associations between the regular use of modelled risk-based 'non-indicated' term labour induction (hereinafter 'preventive induction') and rates of common adverse birth outcomes. SEARCH STRATEGY: MEDLINE and PUBMED databases were searched electronically. SELECTION CRITERIA: Studies were identified that compared term birth outcomes following either the current standard approach with its emphasis on the expectant management of intermediate-level risk or the regular use of preventive induction. DATA COLLECTION AND ANALYSIS: Four studies from four unique databases were identified. A meta-analysis was performed using STATA IC12. MAIN RESULTS: Pregnancies exposed to the regular use of preventive induction (n = 1153), as compared with pregnancies receiving the current standard approach (n = 1865), experienced a lower caesarean delivery rate (5.7% versus 14.4%; relative risk 0.39, 95% CI 0.31-0.50; I(2) P = 0.21), a lower neonatal intensive care unit admission rate (2.9% versus 6.5%; relative risk 0.45, 95% CI 0.31-0.65; I(2) P = 0.57), and a lower weighted adverse outcome index score (2.8 versus 6.1). CONCLUSIONS: The regular use of preventive induction, as compared with the current standard approach, was associated with a more favourable pattern of birth outcomes. Other recently published meta-analyses have also determined that certain types of 'non-indicated' labour induction are beneficial. Accordingly, the current broad restrictions on 'non-indicated' labour induction should be reconsidered. Adequately powered multi-site randomised clinical trials are needed to definitively study the risks and benefits of modelled risk-based 'non-indicated' (i.e. 'preventive') term labour induction.

Tecemotide: an antigen-specific cancer immunotherapy.

The identification of tumor-associated antigens (TAA) has made possible the development of antigen-specific cancer immunotherapies such as tecemotide. One of those is mucin 1 (MUC1), a cell membrane glycoprotein expressed on some epithelial tissues such as breast and lung. In cancer, MUC1 becomes overexpressed and aberrantly glycosylated, exposing the immunogenic tandem repeat units in the extracellular domain of MUC1. Designed to target tumor associated MUC1, tecemotide is being evaluated in Phase III clinical trials for treatment of unresectable stage IIIA/IIIB non-small cell lung cancer (NSCLC) as maintenance therapy following chemoradiotherapy. Additional Phase II studies in other indications are ongoing. This review discusses the preclinical and clinical development of tecemotide, ongoing preclinical studies of tecemotide in human MUC1 transgenic mouse models of breast and lung cancer, and the potential application of these models for optimizing the timing of chemoradiotherapy and tecemotide immunotherapy to achieve the best treatment outcome for patients.