Search

Orthopedic procedures have been associated with increased pain, making perioperative analgesia a major clinical concern. We assessed the efficacy and safety of intravenous parecoxib administration during the perioperative period for postoperative pain relief after orthopedic surgery in adults.PubMed, Cochrane Library, EMBASE, and clinicaltrial.gov were searched from inception to 23 August 2021 without language restrictions. Randomized controlled trials comparing intravenous parecoxib with placebo or another active treatment for acute postoperative pain in adults after orthopedic surgery were included. The primary outcomes were the pain scores and cumulative morphine consumption. The secondary outcomes included the proportion of patients requiring rescue analgesics and the incidence of adverse events. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and was registered on the International Prospective Register of Systematic Reviews Registration (PROSPERO).Twenty-seven trials (n = 2840) from more than 20 countries involving six types of orthopedic surgery met the inclusion criteria. Compared with placebo, intravenous parecoxib administration led to reductions in postoperative resting pain scores at 6, 12, 24, and 48 h [mean difference (MD) -0.87, 95% confidence interval [CI] -1.71 to -0.03; MD -0.86, 95% CI -1.26 to -0.46; MD -0.57, 95% CI -0.84 to -0.31; MD -0.40, 95% CI -0.69 to -0.11, respectively], postoperative movement pain scores at 24 and 48 h (MD -0.66, 95% CI -1.14 to -0.19; MD -0.78, 95% CI -1.16 to -0.39, respectively), cumulative morphine consumption (MD -11.30 mg, 95% CI -14.79 to -7.81 mg), and the proportion of patients requiring rescue analgesia (relative risk 0.83, 95% CI 0.77-0.89). There was no difference in the incidence of adverse events between groups.Low to moderate evidence indicates that parecoxib might be an effective and safe analgesic in perioperative orthopedic settings. It relieves postoperative orthopedic pain while sparing opioid analgesic consumption without increasing the incidence of adverse events.CRD42021274939.

Background: Although antihypertensive medication use is associated with a lower risk of dementia in observational studies, such an effect is rarely found in randomized controlled trials (RCTs). As midlife high blood pressure is more predictive of incident dementia than hypertension in late life, so midlife hypertension may be the target for intervention. However, no such an RCT has been conducted to prevent incident dementia through reducing high blood pressure from midlife. Therefore, we aimed to emulate a target trial with an observational study design to estimate the effect of initiating antihypertensive medication from midlife on reducing incident dementia. Hypothesis: We assessed the hypothesis that newly initiating antihypertensive medication among midlife adults with hypertension reduces incident dementia. Methods: New-user design was used to emulate a target trial using data from the Health and Retirement Study from 1996 to 2018 with non-institutional dementia-free participants aged 45 to 65 years without taking antihypertensive medication in past two years. Participants with information of self-reported hypertension diagnosis and new use of antihypertensive medication, as well as no dementia based on algorithm were included in the analysis and represented group with/without initiating antihypertensive medication. An intention-to-treat approach was applied for analysis, and sequential emulation was used to increase the efficiency of intention-to-treat analysis. Proportional hazards models were applied to estimate the effect of initiating antihypertensive medication on incident dementia. Inverse probability of treatment and censoring weights were created to adjust for confounding and selection bias due to loss to follow-up, and death was considered as a competing event. Another emulated target trial with the same specifications was conducted among late-life adults aged 66 years or older for comparison. Results: A total of 3,151 non-unique participants (baseline mean age: 59.0 ± 4.0 years, 54.6% (n=1,719) women, 78.3% (n=2468) Whites, 71.4% (n=2,249) initiating antihypertensive medication) were included in the analysis. Initiating antihypertensive medication showed benefit in reducing incident dementia over a total of 22-year follow-up, with a reduction of risk by 19% (hazards ratio=0.81, 95% confidence interval: 0.66, 0.99). No significant reduction was observed for initiators of antihypertensive medication from late life. Conclusions: Initiating antihypertensive medication from midlife, but not from late life may reduce incident dementia. Future studies are warranted to estimate the effect of blood pressure lowering in midlife through other means of intervention in reducing incident dementia.

Melanoma can frequently metastasize to the brain with severe consequences. However, variation of melanoma brain metastases (MBM) development among populations is not well studied, and underlying mechanisms and risk factors for MBM development are not consistently documented. We conducted a systematic literature review (SLR) including a total of 39 articles to evaluate the proportion of melanoma patients who are diagnosed with, or develop, brain metastases, and summarize the risk factors of MBM. The average proportion of MBM was calculated and weighted by the sample size of each study. Meta-analyses were conducted for the selected risk factors using a random-effects model. The proportion of MBM at diagnosis was 33% (975 with MBM out of 2948 patients) among patients with cutaneous melanoma (excluding acral) and 23% (651/2875) among patients with cutaneous mixed with other types of melanoma. The proportion at diagnosis was lower among populations with mucosal (9/96, 9%) or uveal (4/184, 2%) melanoma and among populations outside the United States and Europe. Meta-analysis demonstrated that male vs. female gender and left-sided tumors vs. right-sided were significantly associated with increased risk of melanoma brain metastases. These data may help clinicians to assess an individual patient’s risk of developing melanoma brain metastases.

Although researchers have been exploring therapeutic strategies of treating serious periodontal tissue loss, including the application of stem cells, tissue regeneration of the periodontal complex involving cementum, periodontium, and alveolar bone has hardly been achieved. Aiming at tackling the problem of severely damaged periodontal complex, it is worth trying to make advantages of Hertwig's epithelial root sheath (HERS) cells to tissue regeneration mimicking the physiological developmental process with their ability of cementum, bone, and periodontium formation.HERS cells and dental follicle cells (DFCs) were acquired from Sprague Dawley rats' molar germs and identified by immunofluorescence. Alizarin red assay, ALP staining, AKP test, real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot were conducted to confirm the osteogenic potential, epithelial-mesenchymal transition (EMT) character of harvested HERS cells and epithelial-mesenchymal interaction (EMI) with DFCs. An animal model of periodontal defect was constructed to testify the tissue regeneration ability in vivo. Micro-CT and histological examinations were interpreted to unveil the tissue repair outcomes.HERS cells expressed strong epithelial cell markers CK14 and E-cadherin. The in vitro experiments overall showed the concretely enhanced osteogenic differentiation ability in either HERS group or HERS+DFC group. Meanwhile, the in vivo conduction of rat mandibular periodontal repair experiment showed regenerative effectiveness of periodontal complex structure in both HERS and HERS+DFC group in situ, testified by Micro-CT and histological analysis.HERS cells show potential for periodontal tissue regeneration which suggests the future possibilities of being considered as one of the cell choices for severely damaged periodontal tissue repair.

Background: Existing observational studies yielded mixed results between cognitive and dementia outcomes and newer glucose-lowering drugs (GLDs) , i.e., dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs) , and sodium-glucose co-transporter-2 (SGLT2) inhibitors, while individual randomized trials have inadequate power to examine such an effect. Thus, we aimed to evaluate the effect of these newer GLDs on the risk of dementia by performing a meta-analysis of randomized outcome trials. Methods: We included published randomized placebo-controlled cardiovascular and renal outcome trials that evaluated DPP-4 inhibitors, GLP-1RAs, and SGLT2 inhibitors and reported dementia events. The study outcomes were all-cause dementia and vascular dementia, extracted from clinicaltrials.gov. We calculated pooled odds ratios (OR) and 95% CIs using the Peto method. Results: We included 21 trials involving 1all-cause dementia cases (including 22 vascular dementia cases) among 167,5patients with or without type 2 diabetes over a median follow-up of 2.2 years. Neither DPP-4 inhibitors (OR, 0.65 [0.33-1.29]) , GLP-1RAs (OR, 0.88 [0.51-1.52]) , or SGLT2 inhibitors (OR, 1.22 [0.54-2.74]) were significantly associated with all-cause dementia incidence. For vascular dementia, compared with placebo, SGLT2 inhibitors were significantly associated with a decreased risk (OR, 0.[0.02-0.66]) , while DPP-4 inhibitors (OR, 0.67 [0.12-3.85]) and GLP-1RAs (OR, 0.37 [0.12-1.14]) did not significantly decrease the risk. No evidence of statistical heterogeneity or publication bias was detected in the meta-analysis (p >0.05) . Conclusion: SGLT2 inhibitors may have a beneficial effect on lowering the vascular dementia risk, thus may be a drug repurposing signal. Nevertheless, future randomized controlled trials and/or comparative effectiveness studies using real-world data are warranted to further confirm our conclusion. Disclosure H.Tang: None. S.Niu: None. J.D.Brown: None. J.Wei: None. A.G.Winterstein: Consultant; Genentech, Inc., Research Support; Merck & Co., Inc. J.Bian: None. J.Guo: None.

There is significant improvement in the outcomes following treatment with PARP inhibitors among patients with certain tumors that have BRCA mutations (BRCAm), homologous recombination repair (HRR) gene mutations, or homologous recombination deficiency (HRD) positivity. We performed a literature review and meta-analysis to evaluate the prevalence of BRCA1/2m, HRR gene mutations, and HRD positivity across multiple cancers. There were 265 publications on BRCA1/2 mutation prevalence, 189 on HRR gene mutation prevalence, and 7 on HRD positivity prevalence. The prevalences of germline BRCA1m and BRCA2m were 7.8% and 5.7% for breast cancer, 13.5% and 6.6% for ovarian cancer, 0.5% and 3.5% for prostate cancer, and 1.1% and 4.1% for pancreatic cancer, respectively. The prevalences of somatic BRCA1m and BRCA2m were 3.4% and 2.7% for breast cancer, 4.7% and 2.9% for ovarian cancer, 5.7% and 3.2% for prostate cancer, and 1.2% and 2.9% for pancreatic cancer, respectively. We identified 189 studies with over 418,649 samples across 25 tumor types that examined mutations in one or more HRR genes other than BRCA1/2. The prevalence of mutations among HRR genes remained low (less than 1%), with ATM (5.2%), CHEK2 (1.6%), and PALB2 (0.9%) exhibiting the highest prevalence. Seven studies evaluated HRD positivity in breast, ovarian, and prostate cancer patients. The prevalence of HRD positivity was 56% overall (95% CI = 48%-64%). The understanding of biomarker prevalence across tumor types and standardization of biomarker assays could have important clinical implications.

Background and objectives Little is known about the comparative effects of dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), or sodium glucose cotransporter-2 (SGLT2) inhibitors on risk of AKI. This study aimed to compare the effects of these three novel classes of glucose-lowering drugs on AKI risk in patients with or without type 2 diabetes, by network meta-analysis of event-driven cardiovascular or kidney outcome trials. Design, setting, participants, & measurements We systematically searched electronic databases up to September 2020, and included 20 event-driven cardiovascular or kidney outcome trials (18 trials included patients with type 2 diabetes only, and two trials included patients with or without type 2 diabetes). A network meta-analysis using a frequentist approach was performed to compare the effects of DPP-4 inhibitors, GLP-1RAs, or SGLT2 inhibitors on risk of AKI, and estimate the probability for each intervention as the safest one. The primary analysis included 18 trials with type 2 diabetes only, and a secondary analysis included 20 trials. Results In the 18 trials with a total of 2051 AKI events (range: 1–300) among 156,690 patients with type 2 diabetes only, our network meta-analysis showed that SGLT2 inhibitors were associated with a lower risk of AKI compared with placebo (odds ratio, 0.76; 95% confidence interval, 0.66 to 0.88), whereas both DPP-4 inhibitors and GLP-1RAs had neutral effects on risk of AKI. Moreover, SGLT2 inhibitors were significantly associated with a lower risk in AKI than both GLP-1RAs (odds ratio, 0.79; 95% confidence interval, 0.65 to 0.97) and DPP-4 inhibitors (odds ratio, 0.68; 95% confidence interval, 0.54 to 0.86). SGLT2 inhibitors have the highest probability of being the safest intervention (84%). The results were similar in the secondary analysis. Conclusions Current evidence indicates that SGLT2 inhibitors have a lower risk of AKI than both DPP-4 inhibitors and GLP-1RAs.

The SARS-CoV-2 outbreak in 2019 highlighted the fact that no specific medications providing effective treatment have been identified and approved. We explored the possibilities for COVID-19 by systematically reviewing evidence on the efficacy and safety of glycyrrhizin preparations for SARS and MERS. Electronic databases were systematically searched from inception to February 2020 for eligible studies that evaluated the efficacy and safety of glycyrrhizin preparations for SARS and MERS. A quantitative analysis or descriptive analysis was applied. Five retrospective cohort studies were included, and NOS scores ranged from 5–7 points. The clinical symptoms of dry cough, chest distress and dyspnoea improved quickly, and elevated serum levels of aminotransferase decreased after compound glycyrrhizin treatment. The SARS-CoV antibody appeared earlier in the treated group than in the control group ([Formula: see text][Formula: see text]d). Compared to that with conventional medications, the average period from peak to 50% improvement of lesions, in terms of X-ray manifestations, was shorter with compound glycyrrhizin treatment ([Formula: see text]2.1[Formula: see text]d), and treatment reduced the dosage ([Formula: see text][Formula: see text]mg/d) and duration of the corticosteroids used, without other serious adverse reactions. Based on the available evidence regarding glycyrrhizin preparations for treating SARS and MERS, we infer that compound glycyrrhizin could be an optional therapeutic strategy for SARS-CoV-2 infections, especially those complicated with liver damage. Further research using well-designed randomized clinical trials (RCTs) is warranted to determine the dosage and duration of use of compound glycyrrhizin and to monitor its specific adverse effects.

As a new and energetic realm of economic development, an innovative engine of social development, and a strategic tool for shaping national competitiveness, big data significantly effects peoples lives. However, improved social awareness of data value and vigorous development of big data platforms mean that big data security is increasingly hindering the promotion of big data applications. Meanwhile, as big data technology and framework continue to evolve, researchers still have different understandings of the core ideas and key features of big data security, and a unified big data security framework has yet to be established. Currently, determining the state-of-the-art of big data security technology is urgently needed to provide reference for research aimed at solving key big data security issues. Following a typical big data system technology framework, this review builds a novel big data security technology framework around big data security requirements. With this framework, state-of-the-art key big data security technologies are systematically summarized from three aspects: big data secure sharing and trusted services, big data platform security, and big data security supervision, which includes the main security mechanisms involved in big data business processes and system technology frameworks. Finally, big data security technologys core issues and development trends are summarized.

Patients with BRCA1/2 mutations (BRCAm), loss-of-function mutations in other homologous recombination repair (HRRm) genes, or tumors that are homologous recombination deficiency positivity (HRD+) demonstrate a robust response to PARPi therapy. We conducted a systematic literature review and meta-analysis to evaluate the prognostic value of BRCAm, HRRm, and HRD+ on overall survival (OS) among those treated by chemotherapy or targeted therapy other than PARPi across tumor types. A total of 135 eligible studies were included. Breast cancer (BC) patients with BRCA1/2m had a similar overall survival (OS) to those with wild-type BRCA1/2 (BRCA1/2 wt) across 18 studies. Ovarian cancer (OC) patients with BRCA1/2m had a significantly longer OS than those with BRCA1/2 wt across 24 studies reporting BRCA1m and BRCA2m, with an HR of 0.7 (0.6–0.8). Less OS data were reported for other tumors: 6 studies for BRCA2m compared with BRCA2 wt in prostate cancer with an HR of 1.9 (1.1–3.2) and 2 studies for BRCA1/2m compared with BRCA1/2 wt in pancreatic cancer with an HR of 1.5 (0.8–3.1). Only 4 studies reported HRD+ by either BRCA m or genomic instability score (GIS) ≥ 42 and OS by HRD status. The HR was 0.67 (0.43–1.02) for OS with HRD+ vs. HRD−. A total of 15 studies reported the association between HRRm and OS of cancers in which one or more HRR genes were examined. The HR was 1.0 (0.7–1.4) comparing patients with HRRm to those with HRR wild-type across tumors. Our findings are useful in improving the precision and efficacy of treatment selection in clinical oncology.

The electrochemical parameters of cement-based materials with different water–cement ratios in carbon curing and water curing were measured with electrochemical impedance spectroscopy (EIS). The optimized circuit model and corresponding electrical parameters were obtained to illustrate the variation of the microstructure of cementitious materials after carbon capturing. The results show that, to a large extent, the semicircle diameter in the high frequency area gradually increased along with carbon curing and water curing. However, carbon curing showed a difference that the semicircle diameter in the high frequency appeared at the minimal value at 3 days, which was higher than that at 1 day and 7 days. This should be the result of the joint influence of water content and porosity in the cement matrix. It was also found that the mass increase rates of carbonation with water–cement ratios of 0.4, 0.5, and 0.6 were basically stable at 3.4%, 5.0%, and 5.5%, respectively. The electrochemical parameters ρct2 of cement mortar corresponding to carbon curing were around three times that of water curing specimens, mainly due to the reduction of soluble materials and refinement of connecting pores in the microstructure of cementitious materials. A quadratic function correlation between the mass increase rate and ρct2 in the carbonation process of cement mortar was built, which proved that EIS analysis could be applied to monitor the carbon capturing of cement-based materials, either for newly mixed concrete or for recycled concrete aggregates.

BACKGROUND Whether the cardiorenal benefits of sodium–glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) are comparable between White and Asian populations remains unclear. PURPOSE To compare the cardiorenal benefits of SGLT2 inhibitors and GLP-1RAs between White and Asian populations and to compare the cardiorenal benefits between the two agents in Asian patients. DATA SOURCES Electronic databases were searched up to 28 March 2021. STUDY SELECTION We included the cardiovascular (CV) and renal outcome trials of SGLT2 inhibitors and GLP-1RAs where investigators reported major adverse CV events (MACE), CV death/hospitalization for heart failure (HHF), or composite renal outcomes with stratification by race. DATA EXTRACTION We extracted the hazard ratio of each outcome stratified by race (Asian vs. White populations). DATA SYNTHESIS In 10 SGLT2 inhibitor trials, there was no significant difference between Asian and White populations for MACE (P = 0.55), CV death/HHF (P = 0.87), or composite renal outcomes (P = 0.97). In seven GLP-1RA trials, we observed a similar MACE benefit between Asian and White populations (P = 0.10). In our networkmeta-analysis we found a comparable benefit for MACE between SGLT2 inhibitors and GLP-1RAs in Asian patients. LIMITATIONS The data were from stratified analyses. CONCLUSIONS There appear to be comparable cardiorenal benefits of SGLT2 inhibitors and GLP-1RAs between Asian and White participants enrolled in CV and renal outcome trials; the two therapies seem to have similar CV benefits for Asian participants.

Aims This network meta-analysis aimed to evaluate the asthma risk associated with dipeptidyl peptidase (DPP)-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium-glucose co-transporter (SGLT) 2 inhibitors. Methods Electronic databases were systematically searched up to March 2021 to include placebo-controlled cardiovascular (or cardiorenal) outcome trials that reported the asthma incidents in patients taking DPP-4 inhibitors, GLP-1RAs, or SGLT2 inhibitors. A random-effects network meta-analysis was conducted to estimate their odds ratio (ORs) and 95% confidence intervals (CIs). Results Nineteen trials including 218 asthma cases among 159,705 patients were included. Compared with placebo, SGLT2 inhibitors (OR, 0.59; 95% CI, 0.38-0.93) were significantly associated with a decreased risk of asthma while both DPP-4 inhibitors and GLP-1RAs did not significantly affect asthma risk. SGLT2 inhibitors were significantly associated with a lower risk of asthma than DPP-4 inhibitors (OR, 0.38; 95% CI, 0.18-0.79). There was no association between GLP-1RAs and DPP-4 inhibitors and between SGLT2 inhibitors and GLP-1RAs in risk of asthma. Conclusions SGLT2 inhibitors might protect against asthma while DPP-4 inhibitors and GLP-1RAs did not significantly affect the asthma incident. Given the underreporting of asthma in this study, further investigations using real-world data as well as mechanistic studies are warranted to confirm our results.

Background Liver injury has been documented independently in novel coronavirus disease 2019 (COVID-19) patients and patients treated with lopinavir-ritonavir. Objective to investigate the drug-induced liver injury associated with lopinavir-ritonavir among the patients with COVID-19. Methods We conducted a disproportionality analysis of US Food and Drug Administration Adverse Event Reporting System (FAERS) between 2020Q1 and 2020Q3 to evaluate the association between lopinavir-ritonavir and risk of drug-induced liver injury (or severe drug-induced liver injury) and calculated their reporting odds ratios (RORs) with 95% confidence intervals (CIs). Results A total of 1,754 reports of drug-induced liver injury in patients with COVID-19. The ROR for drug-induced liver injury was 1.4 (95% CI, 1.1–1.7), 3.6 (95% CI, 2.7–4.7), and 0.8 (95% CI, 0.7-1.0) when comparing lopinavir-ritonavir with all other drugs, hydroxychloroquine/chloroquine only, and remdesivir, respectively. For severe drug-induced liver injury, RORs for lopinavir-ritonavir provided evidence of an association compared with all other drugs (ROR, 4.9; 95% CI, 3.7–6.5), compared with hydroxychloroquine/chloroquine only (ROR, 4.3; 95% CI, 3.0-6.2), and compared with remdesivir (ROR, 10.4; 95% CI, 7.2–15.0). Conclusions In the FAERS, we observed a disproportional signal for severe drug-induced liver injury associated with lopinavir-ritonavir in patients with COVID-19.

Background Liver injury has been documented independently in novel coronavirus disease 2019 (COVID-19) patients and patients treated with lopinavir-ritonavir. Objective to investigate the drug-induced liver injury associated with lopinavir-ritonavir among the patients with COVID-19. Methods We conducted a disproportionality analysis of US Food and Drug Administration Adverse Event Reporting System (FAERS) between 2020Q1 and 2021Q1 to evaluate the association between lopinavir-ritonavir and risk of drug-induced liver injury (or severe drug-induced liver injury) and calculated their reporting odds ratios (RORs) with 95% confidence intervals (CIs). Results A total of 3,425 cases of drug-induced liver injury were reported in 19,782 patients with COVID-19. The ROR for drug-induced liver injury was 2.99 (2.59–3.46), 3.16 (2.68–3.73), and 5.39 (4.63–6.26) when comparing lopinavir-ritonavir with all other drugs, hydroxychloroquine/chloroquine only, and remdesivir, respectively. For severe drug-induced liver injury, RORs for lopinavir-ritonavir provided evidence of an association compared with all other drugs (3.98; 3.15–5.05), compared with hydroxychloroquine/chloroquine only (5.33; 4.09–6.94), and compared with remdesivir (3.85; 3.03–4.89). Conclusions In the FAERS, we observed a disproportional signal for drug-induced liver injury associated with lopinavir-ritonavir in patients with COVID-19.

Background Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by enlarged ovaries and an acute fluid shift from the intravascular space to the third space, resulting in bloating, increased risk of venous thromboembolism and decreased organ perfusion. Most cases are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. The dopamine agonist cabergoline was introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS undergoing ART treatment. As cabergoline seemed to be effective in preventing OHSS, other types of dopamine agonists, such as quinagolide and bromocriptine, have since been studied in ART to prevent OHSS. Objectives To assess the effectiveness and safety of dopamine agonists in preventing OHSS in high-risk women undergoing ART treatment. Search methods We searched several databases from inception to August 2016 (Cochrane Gynaecology and Fertility Specialised Register of trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, PsycINFO, Clinicaltrials.gov and the World Health Organization International Trials Registry Platform (ICTRP)) for randomised controlled trials (RCTs) assessing the effect of dopamine agonist in preventing OHSS. We handsearched the reference lists of relevant studies. Selection criteria We considered RCTs which compared dopamine agonists with placebo/no intervention or another intervention for preventing OHSS in high-risk women for inclusion. Primary outcome measures were incidence of moderate or severe OHSS and live birth rate. Secondary endpoints were clinical pregnancy rate, multiple pregnancy rate, miscarriage rate and any other adverse effects of the treatment. Data collection and analysis Two authors independently screened titles, abstracts and full texts of publications, selected studies, extracted data and assessed risk of bias. We resolved any disagreements by consensus. We reported pooled results as odds ratios (OR) and 95% confidence interval (95% CI) by the Mantel-Haenszel method. In addition, we graded the overall quality of the evidence using GRADE criteria. Main results The search identified 14 new RCTs since the last published version of this review, resulting in 16 included RCTs involving 2091 high-risk women for this updated review. They evaluated three types of dopamine agonists: cabergoline, quinagolide and bromocriptine. When compared with placebo or no intervention, dopamine agonists seemed effective in the prevention of moderate or severe OHSS (OR 0.27, 95% CI 0.19 to 0.39; 1022 participants; 8 studies; I2 = 0%; moderate quality evidence). This suggests that if 29% of women undergoing ART experience moderate or severe OHSS, the use of dopamine agonists will lower this to 7% to 14% of women. There was no evidence of a difference in live birth rate, clinical pregnancy rate, multiple pregnancy rate or miscarriage rate (very low to moderate quality evidence). However, taking dopamine agonists (especially quinagolide) may increase the incidence of adverse events such as gastrointestinal adverse effects (OR 4.54, 95% CI 1.49 to 13.84; 264 participants; 2 studies; I2 = 49%, very low quality evidence). When we compared dopamine agonist plus co-intervention with co-intervention, there was no evidence of a difference in the outcomes of moderate or severe OHSS, live birth rate, clinical pregnancy rate, miscarriage rate or adverse events. The co-interventions were hydroxyethyl starch (two RCTs) and albumin (one RCT). Cabergoline was associated with a lower risk of moderate or severe OHSS compared with human albumin (OR 0.21, 95% CI 0.12 to 0.38; 296 participants; 3 studies; I2 = 72%). However, there was no evidence of a difference between cabergoline and hydroxyethyl starch, coasting (withholding any more ovarian stimulation for a few days) or prednisolone. There was an increased clinical pregnancy rate in the cabergoline group when cabergoline was compared with coasting (OR 2.65, 95% CI 1.13 to 6.21; 120 participants; 2 studies; I2 = 0%). In other respects, there was no evidence of a difference in clinical pregnancy rate, multiple pregnancy rate or miscarriage rate between cabergoline and other active interventions. The quality of the evidence between dopamine agonist and placebo or no intervention ranged from very low to moderate, mainly due to poor reporting of study methods (mostly a lack of details on randomisation or blinding) and serious imprecision for some comparisons. Authors' conclusions Dopamine agonists appear to reduce the incidence of moderate or severe OHSS in women at high risk of OHSS (moderate quality evidence). If a fresh embryo transfer is performed, the use of dopamine agonists does not affect the pregnancy outcome (live birth rate, clinical pregnancy rate and miscarriage rate) (very low to moderate quality evidence). However, dopamine agonists might increase the risk of adverse events, such as gastrointestinal symptoms. Further research should focus on dose-finding, comparisons with other effective treatments and consideration of combination treatments. Therefore, large, well-designed and well-executed RCTs that involve more clinical endpoints (e.g., live birth rate) are necessary to further evaluate the role of dopamine agonists in OHSS prevention.

In this Letter, a new class of an accelerating self-imaging surface plasmonic wave, the Airy–Talbot plasmon, is introduced for the first time, to the best of our knowledge. Our research shows that such a surface wave propagates at the interface between metal (silver) and a dielectric material (air) and causes a strong interference along curved trajectories, which generates the Talbot effect in the surface. The propagation properties have potential value in nanoscale plasmonic devices. A scheme for generating this novel plasmon theoretically is proposed, and we prove it by finite difference time-domain numerical simulations.

Background Traditional Chinese medicine (TCM) is one of the major triggers for drug-induced anaphylaxis (DIA). Objective We aimed to use the Beijing pharmacovigilance database (BPD) to analyze TCM-induced DIAs in Beijing, China. Setting Drug allergy case reports from the BPD provided by the Beijing Center for Adverse Drug Reaction Monitoring. Method Drug allergy cases from January 2004 to December 2014 were adjudicated. DIA triggered by TCMs were analyzed and compared with those triggered by non-TCM drugs by calculating the reported risk ratio (RRR). We also calculated the RRRs based on severe DIA and death outcomes. Main outcome measure TCMs implicated in DIAs were identified and compared with non-TCM drugs. Results TCMs accounted for 1651 (18.2%) of the total 9074 allergic cases, in which 84.4% (1393/1651) were triggered by injections. Of the TCM allergic cases, 8.5% (141) were DIAs and 7.3% (120) were severe DIAs, and three patients died from injections. The RRR between TCMs and non-TCM-induced DIAs was 0.63. When anaphylactic cases were compared between TCMs to the top four non-TCM drug triggers, RRRs were 0.73 (95% CI 0.61-0.87) for antibiotics, 0.36 (95% CI 0.29-0.44) for radiocontrast agents, 0.55 (95% CI 0.43-0.68) for chemotherapeutics, and 0.29 (95% CI 0.23-0.37) for biologics. Compared to TCM oral or topic formulations, TCM injections had higher RRRs in each of the above comparisons. Conclusion TCM was associated with a decreased risk of DIA compared to non-TCM drugs in drug allergy cases, and the risk was higher for TCM injections.

Aim To assess the comparative effects of glucose-lowering drugs (GLDs) on the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods We systematically searched Cochrane Central Register of Controlled Trials, PUBMED and EMBASE from inception to January 17, 2017 to identify randomized controlled trials (RCTs) that reported DR events among T2DM patients receiving any GLD. Random-effects pairwise and network meta-analyses were performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Results A total of 37 independent RCTs with 1806 DR events among 100 928 patients with T2DM were included. The mean duration of diabetes was 8.7 years and mean baseline HbA1c was 8.2% (SD, 0.5%). Our network meta-analysis found that DPP-4i (OR, 1.20; 95% CI, 0.87-1.65), GLP-1RA (OR, 1.19; 95% CI, 0.94-1.52) and SGLT2 inhibitors (OR, 0.79; 95% CI, 0.49-1.28) were not associated with a higher risk of DR than placebo; however, a significantly increased risk of DR was associated with DPP-4i in the pairwise meta-analysis (OR, 1.27; 95% CI, 1.05-1.53). Sulfonylureas, on the other hand, were associated with a significantly increased risk of DR compared to placebo (OR, 1.67; 95% CI, 1.01-2.76). Conclusions Current evidence indicates that the association between DPP-4i, GLP-1RA or SGLT2 inhibitors and risk of DR remains uncertain in patients with T2DM. Some evidence suggests that sulfonylureas may be associated with increased risk of DR. However, given that DR events were not systematically assessed, these effects should be explored further in large-scale, well-designed studies.

Current evidence about the association between pioglitazone and bladder cancer risk remains conflict. We aimed to assess the risk of bladder cancer associated with the use of pioglitazone and identify modifiers that affect the results. We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception to 25 August 2016 for randomized controlled trials (RCTs) and observational studies that evaluated the association between pioglitazone and bladder cancer risk. Conventional and cumulative meta‐analyses were used to calculate the odds ratio (OR) with 95% confidence interval (CI). A restricted spline regression analysis was used to examine the dose–response relationship with a generalized least‐squares trend test. We included two RCTs involving 9114 patients and 20 observational studies (n = 4,846,088 individuals). An increased risk of bladder cancer in patients treated with pioglitazone versus placebo was noted from RCTs (OR, 1.84; 95%CI, 0.99 to 3.42). In observational studies, the increased risk of bladder cancer was slight but significant among ever‐users of pioglitazone versus never‐users (OR, 1.13; 95%CI, 1.03 to 1.25), which appeared to be both time‐ (P = 0.003) and dose‐dependent (P = 0.05). In addition, we observed the association differed by region of studies (Europe, United States, or Asia) or source of funding (sponsored by industry or not). Current evidence suggests that pioglitazone may increase the risk of bladder cancer, possibly in a dose‐ and time‐dependent manner. Patients with long‐term and high‐dose exposure to pioglitazone should be monitored regularly for signs of bladder cancer.

Purpose Current epidemiologic evidence on the association between antihypertensive drugs and keratinocyte carcinoma (KC) risk is inconsistent. We sought to quantify this association by meta-analysis of observational studies. Methods We systematically reviewed observational studies published through August 2016 and reported the KC risk (basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]) associated with antihypertensive drugs, including diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-adrenergic blocking agents (β-blockers), and calcium channel blockers (CCBs). Random-effects meta-analysis was used to estimate the odds ratio (OR) with 95% confidence interval (CI). Results Ten eligible studies were included. Compared with nonuse, diuretic use was significantly associated with increased risk of both BCC (OR, 1.10; 95% CI, 1.01-1.20) and SCC (OR, 1.40; 95% CI, 1.19-1.66). Use of β-blockers or CCBs was associated with increased risk of BCC (but not SCC); the OR with β-blockers was 1.09 (95% CI, 1.04-1.15) and with CCBs was 1.15 (95% CI, 1.09-1.21). Use of ACE inhibitors or ARBs was associated with decreased risk of both BCC (OR, 0.53; 95% CI, 0.39-0.71) and SCC (OR, 0.58; 95% CI, 0.42-0.80) in high-risk individuals. Conclusions Current evidence indicates that use of diuretics might be associated with increased risk of KC, while ACE inhibitors or ARBs might be associated with decreased risk in high-risk individuals. β-blockers or CCBs might be positively associated with BCC risk. Further postmarketing surveillance studies and investigations to clarify the possible underlying mechanisms are warranted.