Association of education attainment, smoking status, and alcohol use disorder with dementia risk in older adults: a longitudinal observational study.

BACKGROUND: Previous research on the risk of dementia associated with education attainment, smoking status, and alcohol use disorder (AUD) has yielded inconsistent results, indicating potential heterogeneous treatment effects (HTEs) of these factors on dementia risk. Thus, this study aimed to identify the important variables that may contribute to HTEs of these factors in older adults. METHODS: Using 2005-2021 data from the National Alzheimer's Coordinating Center (NACC), we included older adults (≥ 65 years) with normal cognition at the first visit. The exposure of interest included college education or above, current smoking, and AUD and the outcome was all-cause dementia. We applied doubly robust learning to estimate risk differences (RD) and 95% confidence intervals (CI) between exposed and unexposed groups in the overall cohort and subgroups identified through a decision tree model. RESULTS: Of 10,062 participants included, 929 developed all-cause dementia over a median 4.4-year follow-up. College education or above was associated with a lower risk of all-cause dementia in the overall population (RD, -1.5%; 95%CI, -2.8 to -0.3), especially among the subpopulations without hypertension, regardless of the APOE4 status. Current smoking was not related to increased dementia risk overall (2.8%; -1.5 to 7.2) but was significantly associated with increased dementia risk among men with (21.1%, 3.1 to 39.1) and without (8.4%, 0.9 to 15.8) cerebrovascular disease. AUD was not related to increased dementia risk overall (2.0%; -7.7 to 11.7) but was significantly associated with increased dementia risk among men with neuropsychiatric disorders (31.5%; 7.4 to 55.7). CONCLUSIONS: Our studies identified important factors contributing to HTEs of education, smoking, and AUD on risk of all-cause dementia, suggesting an individualized approach is needed to address dementia disparities.

A xenogeneic extracellular matrix-based 3D printing scaffold modified by ceria nanoparticles for craniomaxillofacial hard tissue regeneration via osteo-immunomodulation.

Hard tissue engineering scaffolds especially 3D printed scaffolds were considered an excellent strategy for craniomaxillofacial hard tissue regeneration, involving crania and facial bones and teeth. Porcine treated dentin matrix (pTDM) as xenogeneic extracellular matrix has the potential to promote the stem cell differentiation and mineralization as it contains plenty of bioactive factors similar with human-derived dentin tissue. However, its application might be impeded by the foreign body response induced by the damage-associated molecular patterns of pTDM, which would cause strong inflammation and hinder the regeneration. Ceria nanoparticles (CNPs) show a great promise at protecting tissue from oxidative stress and influence the macrophages polarization. Using 3D-bioprinting technology, we fabricated a xenogeneic hard tissue scaffold based on pTDM xenogeneic TDM-polycaprolactone (xTDM/PCL) and we modified the scaffolds by CNPs (xTDM/PCL/CNPs). Through series ofin vitroverification, we found xTDM/PCL/CNPs scaffolds held promise at up-regulating the expression of osteogenesis and odontogenesis related genes including collagen type 1, Runt-related transcription factor 2 (RUNX2), bone morphogenetic protein-2, osteoprotegerin, alkaline phosphatase (ALP) and DMP1 and inducing macrophages to polarize to M2 phenotype. Regeneration of bone tissues was further evaluated in rats by conducting the models of mandibular and skull bone defects. Thein vivoevaluation showed that xTDM/PCL/CNPs scaffolds could promote the bone tissue regeneration by up-regulating the expression of osteogenic genes involving ALP, RUNX2 and bone sialoprotein 2 and macrophage polarization into M2. Regeneration of teeth evaluated on beagles demonstrated that xTDM/PCL/CNPs scaffolds expedited the calcification inside the scaffolds and helped form periodontal ligament-like tissues surrounding the scaffolds.

CDC42-mediated Wnt signaling facilitates odontogenic differentiation of DPCs during tooth root elongation.

BACKGROUND: CDC42 is a member of Rho GTPase family, acting as a molecular switch to regulate cytoskeleton organization and junction maturation of epithelium in organ development. Tooth root pattern is a highly complicated and dynamic process that dependens on interaction of epithelium and mesenchyme. However, there is a lack of understanding of the role of CDC42 during tooth root elongation. METHODS: The dynamic expression of CDC42 was traced during tooth development through immunofluorescence staining. Then we constructed a model of lentivirus or inhibitor mediated Cdc42 knockdown in Herwig's epithelial root sheath (HERS) cells and dental papilla cells (DPCs), respectively. Long-term influence of CDC42 abnormality was assessed via renal capsule transplantation and in situ injection of alveolar socket. RESULTS: CDC42 displayed a dynamic spatiotemporal pattern, with abundant expression in HERS cells and apical DPCs in developing root. Lentivirus-mediated Cdc42 knockdown in HERS cells didn't disrupt cell junctions as well as epithelium-mesenchyme transition. However, inhibition of CDC42 in DPCs undermined cell proliferation, migration and odontogenic differentiation. Wnt/ß-catenin signaling as the downstream target of CDC42 modulated DPCs' odontogenic differentiation. The transplantation and in situ injection experiments verified that loss of CDC42 impeded root extension via inhibiting the proliferation and differentiation of DPCs. CONCLUSIONS: We innovatively revealed that CDC42 was responsible for guiding root elongation in a mesenchyme-specific manner. Furthermore, CDC42-mediated canonical Wnt signaling regulated odontogenic differentiation of DPCs during root formation.

Personalized 3D-Printed Scaffolds with Multiple Bioactivities for Bioroot Regeneration.

Recent advances in 3D printing offer a prospective avenue for producing transplantable human tissues with complex geometries; however, the appropriate 3D-printed scaffolds possessing the biological compatibility for tooth regeneration remain unidentified. This study proposes a personalized scaffold of multiple bioactivities, including induction of stem cell proliferation and differentiation, biomimetic mineralization, and angiogenesis. A brand-new bioink system comprising a biocompatible and biodegradable polymer is developed and reinforced with extracellular matrix generated from dentin tissue (treated dentin matrix, TDM). Adding TDM optimizes physical properties including microstructure, hydrophilicity, and mechanical strength of the scaffolds. Proteomics analysis reveals that the released proteins of the 3D-printed TDM scaffolds relate to multiple biological processes and interact closely with each other. Additionally, 3D-printed TDM scaffolds establish a favorable microenvironment for cell attachment, proliferation, and differentiation in vitro. The 3D-printed TDM scaffolds are proangiogenic and facilitate whole-thickness vascularization of the graft in a subcutaneous model. Notably, the personalized TDM scaffold combined with dental follicle cells mimics the anatomy and physiology of the native tooth root three months after in situ transplantation in beagles. The remarkable in vitro and in vivo outcomes suggest that the 3D-printed TDM scaffolds have multiple bioactivities and immense clinical potential for tooth-loss therapy.

Hertwig's epithelial root sheath cells show potential for periodontal complex regeneration.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Burden and Risk Factors of Brain Metastases in Melanoma: A Systematic Literature Review.

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.

Systematic literature review and meta-analysis of clinical outcomes and prognostic factors for melanoma brain metastases.

Background: More than 60% of all stage IV melanoma patients develop brain metastases, while melanoma brain metastases (MBM) is historically difficult to treat with poor prognosis. Objectives: To summarize clinical outcomes and prognostic factors in MBM patients. Methods: A systematic review with meta-analysis was conducted, and a literature search for relevant studies was performed on November 1, 2020. Weighted average of median overall survival (OS) was calculated by treatments. The random-effects model in conducting meta-analyses was applied. Results: A total of 41 observational studies and 12 clinical trials with our clinical outcomes of interest, and 31 observational studies addressing prognostic factors were selected. The most common treatments for MBM were immunotherapy (IO), MAP kinase inhibitor (MAPKi), stereotactic radiosurgery (SRS), SRS+MAPKi, and SRS+IO, with median OS from treatment start of 7.2, 8.6, 7.3, 7.3, and 14.1 months, respectively. Improved OS was observed for IO and SRS with the addition of IO and/or MAPKi, compared to no IO and SRS alone, respectively. Several prognostic factors were found to be significantly associated with OS in MBM. Conclusion: This study summarizes pertinent information regarding clinical outcomes and the association between patient characteristics and MBM prognosis.

A comprehensive literature review and meta-analysis of the prevalence of pan-cancer BRCA mutations, homologous recombination repair gene mutations, and homologous recombination deficiencies.

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.

A Systematic Review and Meta-Analysis on the Prognostic Value of BRCA Mutations, Homologous Recombination Gene Mutations, and Homologous Recombination Deficiencies in Cancer.

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.

Intravenous Parecoxib for Pain Relief after Orthopedic Surgery: A Systematic Review and Meta-analysis.

INTRODUCTION: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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. PROSPERO REGISTRATION: CRD42021274939.

Pancreatic safety of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

PURPOSE: This study aimed to systematically evaluate the association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and pancreatic safety in patients with type 2 diabetes mellitus (T2DM). METHODS: Electronic databases were searched before September 2019 to include randomized controlled trials (RCTs) of SGLT2 inhibitors that reported any event on pancreatitis or pancreatic cancer among patients with T2DM. Peto odds ratio (OR) with 95% confidence interval (CI) was used to pool the data. The GRADE framework was introduced to assess the quality of evidence. RESULTS: Of the 35 trials involving 44 912 patients with T2DM included, 41 events of acute pancreatitis (19 trials; 32 932 patients), 72 events of overall pancreatitis (including acute pancreatitis, chronic pancreatitis, or nonspecific pancreatitis; 26 trials; 36 688 patients), and 40 events of pancreatic cancer (18 trials; 27 806 patients) were reported during a median follow-up of 52 weeks. SGLT2 inhibitors were not associated with an increased risk of acute pancreatitis compared to controls (placebo or other active drugs; Peto OR, 1.13; 95% CI, 0.60-2.13; moderate quality evidence). A similar result was found for risk of overall pancreatitis (Peto OR, 1.08; 95% CI, 0.67-1.75; moderate quality evidence) and pancreatic cancer (Peto OR, 1.34; 95% CI, 0.71-2.54; very low-quality evidence). CONCLUSIONS: Moderate quality evidence from RCTs shows no significantly increased risk of acute pancreatitis associated with SGLT2 inhibitors, while there is very low-quality evidence suggesting no significant association between SGLT2 inhibitors and pancreatic cancer among patients with T2DM.

Dipeptidyl Peptidase 4 Inhibitors and Risk of Inflammatory Bowel Disease: Real-world Evidence in U.S. Adults.

OBJECTIVE: A recent study raises concerns that dipeptidyl peptidase 4 inhibitors (DPP4i) are associated with increased risk of inflammatory bowel disease (IBD). We evaluated the association between new use of DPP4i and IBD risk compared with other second-line antihyperglycemics. RESEARCH DESIGN AND METHODS: We implemented an active-comparator, new-user cohort design using two U.S. administrative claims databases for commercially insured (MarketScan) and older adult (Medicare fee-for-service, 20% random sample) patients from January 2007 to December 2016. We identified patients, aged ≥18 years, who initiated DPP4i versus sulfonylureas (SUs) or initiated DPP4i versus thiazolidinediones (TZDs) and were without prior diagnosis, treatment, or procedure for IBD. The primary outcome was incident IBD, defined by IBD diagnosis preceded by colonoscopy and biopsy and followed by IBD treatment. We performed propensity score weighting to control for measured baseline confounding, estimated adjusted hazard ratios (aHRs [95% CI]) using weighted Cox proportional hazards models, and used random-effects meta-analysis models to pool aHRs across cohorts. RESULTS: We identified 895,747 eligible patients initiating DPP4i, SU, or TZD; IBD incidence rates ranged from 11.6 to 32.3/100,000 person-years. Over a median treatment duration of 1.09-1.69 years, DPP4i were not associated with increased IBD risk across comparisons. The pooled aHRs for IBD were 0.82 (95% CI 0.41-1.61) when comparing DPP4i (n = 161,612) to SU (n = 310,550) and 0.76 (0.46-1.26) when comparing DPP4i (n = 205,570) to TZD (n = 87,543). CONCLUSIONS: Our population-based cohort study of U.S. adults with diabetes suggests that short-term DPP4i treatment does not increase IBD risk.

Voriconazole exposure and risk of cutaneous squamous cell carcinoma among lung or hematopoietic cell transplant patients: A systematic review and meta-analysis.

BACKGROUND: Current evidence about the association between voriconazole and risk of cutaneous squamous cell carcinoma (SCC) remains inconsistent. OBJECTIVE: To assess the association between voriconazole use and risk of SCC. METHODS: We systematically searched PubMed and Embase and performed a random effects model meta-analysis to calculate the pooled relative risk (RR) with a 95% confidence interval (CI). RESULTS: Of the 8 studies involving a total of 3710 individuals with a lung transplant or hematopoietic cell transplant that were included in the qualitative analysis, 5 were included in the meta-analysis. Use of voriconazole was significantly associated with increased risk of SCC (RR, 1.86; 95% CI, 1.36-2.55). The increased risk did not differ according to type of transplantation or adjustment for sun exposure. Longer duration of voriconazole use was found to be positively associated with risk of SCC (RR, 1.72; 95% CI, 1.09-2.72). Voriconazole use was not associated with increased risk of basal cell carcinoma (RR, 0.84; 95% CI, 0.41-1.71). LIMITATIONS: There were some heterogeneities in the retrospective observational studies. CONCLUSIONS: Our findings support an increased risk of SCC associated with voriconazole in individuals with a lung transplant or hematopoietic cell transplant. Routine dermatologic surveillance should be performed, especially among individuals at high risk of developing SCC.

Meta-analysis of the association between sodium-glucose co-transporter-2 inhibitors and risk of skin cancer among patients with type 2 diabetes.

A slight increase in melanoma risk was observed among sodium-glucose co-transporter-2 (SGLT-2) inhibitor users in the regular reports. However, the association remains uncertain. To address this issue, we performed a systematic search of electronic databases up to May 2, 2018 and a meta-analysis of 21 randomized controlled trials (RCTs) involving 20 308 patients. We did not find a significant increase in risk of melanoma among SGLT-2 inhibitor users (Peto odds ratio [OR], 2.17; 95% confidence interval [CI], 0.80-5.89; I2 , 0%). Similar results were observed in the subgroup analyses according to the type of SGLT-2 inhibitor, type of control, ages of patients, race/ethnicity, and trial durations. For non-melanoma skin cancer risk, no significant difference was observed when all trials were combined (Peto OR, 0.70; 95% CI, 0.47-1.07; I2 , 0%), while a significantly decreased risk was observed among trials with duration <52 weeks (Peto OR, 0.12; 95% CI, 0.02-0.59; I2 , 0%). No evidence of publication bias was detected in the analyses. Current evidence from RCTs did not support a significantly increased risk of skin cancer associated with SGLT-2 inhibitors.

Pioglitazone and bladder cancer risk: a systematic review and meta-analysis.

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.

Use of antihypertensive drugs and risk of keratinocyte carcinoma: A meta-analysis of observational studies.

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 (ß-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 ß-blockers or CCBs was associated with increased risk of BCC (but not SCC); the OR with ß-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. ß-blockers or CCBs might be positively associated with BCC risk. Further postmarketing surveillance studies and investigations to clarify the possible underlying mechanisms are warranted.

Drug-induced anaphylaxis in China: a 10 year retrospective analysis of the Beijing Pharmacovigilance Database.

Background Few studies on the causes of drug-induced anaphylaxis (DIA) in the hospital setting are available. Objective We aimed to use the Beijing Pharmacovigilance Database (BPD) to identify the causes of DIA in Beijing, China. Setting Anaphylactic case reports from the BPD provided by the Beijing Center for Adverse Drug Reaction Monitoring. Method DIA cases collected by the BPD from January 2004 to December 2014 were adjudicated. Cases were analyzed for demographics, causative drugs and route of administration, and clinical signs and outcomes. Main outcome measure Drugs implicated in DIAs were identified and the signs and symptoms of the DIA cases were analyzed. Results A total of 1189 DIA cases were analyzed. The mean age was 47.6 years, and 732 (61.6%) were aged from 18 to 59 years. A total of 627 patients (52.7%) were females. There was a predominance of cardiovascular (83.8%) followed by respiratory (55.4%), central nervous (50.1%), mucocutaneous (47.4%), and gastrointestinal symptoms (31.3%). A total of 249 different drugs were involved. DIAs were mainly caused by antibiotics (39.3%), traditional Chinese medicines (TCM) (11.9%), radiocontrast agents (11.9%), and antineoplastic agents (10.3%). Cephalosporins accounted for majority (34.5%) of antibiotic-induced anaphylaxis, followed by fluoroquinolones (29.6%), beta-lactam/beta-lactamase inhibitors (15.4%) and penicillins (7.9%). Blood products and biological agents (3.1%), and plasma substitutes (2.1%) were also important contributors to DIAs. Conclusion A variety of drug classes were implicated in DIAs. Patients should be closely monitored for signs and symptoms of anaphylaxis when medications are administered especially with antibiotics, TCM, radiocontrast and antineoplastic agents.

Use of Antihypertensive Drugs and Risk of Malignant Melanoma: A Meta-analysis of Observational Studies.

INTRODUCTION: Several antihypertensive drugs are photosensitizing and may promote the development of malignant melanoma (MM), but evidence remains inconsistent. We sought to quantify the association between use of antihypertensive drugs and MM risk. METHODS: We systematically searched PubMed, Embase, and CENTRAL from inception to August 17, 2017 to identify observational studies that reported the MM risk associated with the use of antihypertensive drugs. A random-effects meta-analysis was used to estimate the odds ratio (OR) with 95% confidence interval (CI). RESULTS: Overall, we included eight observational studies (two cohort studies and six case-control studies). Compared with non-use, use of diuretics (OR 1.10; 95% CI 1.03-1.17) or ß-adrenergic blocking agents (OR 1.19; 95% CI 1.04-1.37) was significantly associated with increased risk of MM. The use of angiotensin-converting enzyme inhibitors (OR 1.08; 95% CI 0.95-1.23), angiotensin II receptor blockers (OR 1.12; 95% CI 0.95-1.31), and calcium channel blockers (OR 1.12; 95% CI 0.72-1.74) was not significantly associated with increased risk of MM. CONCLUSIONS: Current evidence from observational studies suggests that use of diuretics or ß-adrenergic blocking agents may be associated with increased risk of MM. Further large well-conducted prospective studies are required to confirm our findings.

Statin use and non-melanoma skin cancer risk: a meta-analysis of randomized controlled trials and observational studies.

BACKGROUND: Existing evidence of the association between statin use and non-melanoma skin cancer (NMSC) risk has been inconsistent. OBJECTIVE: To maximize statistical power to synthesize prospective evidence on this relationship. MATERIALS AND METHODS: PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrial.gov were systematically searched up to December 11, 2016. A random-effects meta-analysis was conducted to calculate summary estimates. RESULTS: Our meta-analysis of 14 randomized controlled trials (RCTs) including 63,157 subjects showed no significant association between statin use and NMSC risk (RR = 1.09, 95%CI = 0.85-1.39). However, meta-analysis of four observational studies including 1,528,215 participants showed significantly increased risk of NMSC among statin users compared to non-users (RR = 1.11, 95%CI = 1.02-1.22). Furthermore, ever using lipophilic statins (RR = 1.14, 95%CI = 1.04-1.24) or lower-potency statins (RR = 1.14, 95%CI = 1.03-1.26), as well as usage of any statin longer than one year (RR = 1.14, 95%CI = 1.09-1.18) were significantly associated with increased NMSC risk based on observational studies. CONCLUSIONS: Evidence from observational studies supported an association between statin use and increased NMSC risk. This finding should be interpreted with caution due to modest number of included studies, possible between-study heterogeneity and inherent limitations of observational studies.