Real-life drug-drug and herb-drug interactions in outpatients taking oral anticancer drugs: comparison with databases.

PURPOSE: Due to polypharmacy and the rising popularity of complementary and alternative medicines (CAM), oncology patients are particularly at risk of drug-drug interactions (DDI) or herb-drug interactions (HDI). The aims of this study were to assess DDI and HDI in outpatients taking oral anticancer drug. METHOD: All prescribed and non-prescribed medications, including CAM, were prospectively collected by hospital pharmacists during a structured interview with the patient. DDI and HDI were analyzed using four interaction software programs: Thériaque®, Drugs.com®, Hédrine, and Memorial Sloan Kettering Cancer Center (MSKCC) database. All detected interactions were characterized by severity, risk and action mechanism. The need for pharmaceutical intervention to modify drug use was determined on a case-by-case basis. RESULTS: 294 patients were included, with a mean age of 67 years [55-79]. The median number of chronic drugs per patient was 8 [1-29] and 55% of patients used at least one CAM. At least 1 interaction was found for 267 patients (90.8%): 263 (89.4%) with DDI, 68 (23.1%) with HDI, and 64 (21.7%) with both DDI and HDI. Only 13% of the DDI were found in Thériaque® and Drugs.com® databases, and 125 (2.5%) were reported with similar level of risk on both databases. 104 HDI were identified with only 9.5% of the interactions found in both databases. 103 pharmaceutical interventions were performed, involving 61 patients (20.7%). CONCLUSION: Potentially clinically relevant drug interaction were frequently identified in this study, showing that several databases and structured screening are required to detect more interactions and optimize medication safety.

Incidence of Sympathetic Ophthalmia after Inciting Events: A National Database Study in Japan.

PURPOSE: To analyze the incidence of sympathetic ophthalmia (SO) after inciting events (eye trauma or intraocular surgery). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients experiencing inciting events between 2012 and 2019. Onset of SO was defined as the first date of SO diagnosis. METHODS: Using a nationwide administrative claims database in Japan, we calculated the cumulative incidence of SO after inciting events stratified by sex, 10-year age groups, and a categorical variable of primary or repeated, reflecting the history of inciting events in the past year (no inciting events, inciting events without trauma, or inciting events with trauma) using the Kaplan-Meier approach. We also estimated the adjusted hazard ratio (aHR) by Cox regression. We then restricted the population to those with only 1 inciting event during the observation period to investigate the pure effect of each inciting event. MAIN OUTCOME MEASURES: Cumulative incidence of SO over 60 months. RESULTS: A total of 888 041 inciting events (704 717 patients) were eligible. The total number of SO cases was 263, and the cumulative incidence of SO was 0.044% over 60 months. Female sex was not associated with onset of SO (aHR, 1.01; 95% confidence interval [CI], 0.79-1.29; P = 0.95). The group 40 to 49 years of age showed the highest incidence of 0.104% among the age groups (aHR vs. ≥80 years of age group [0.041%], 2.44 [95% CI, 1.56-3.80]; P < 0.001). Repeated inciting events with and without trauma showed higher incidences of SO (0.469% and 0.072%, respectively) than primary inciting events (0.036%) (aHR 11.68 [7.74-17.64] and 2.21 [95% CI, 1.59-3.07], respectively); P < 0.001 and P < 0.001, respectively). The incidence of SO after vitrectomy was much lower than after trauma (0.016% vs. 0.073%), and the incidence after scleral buckling was even lower. CONCLUSIONS: The cumulative incidence of SO over 60 months was estimated to be 0.044% at minimum. Repeated inciting events, especially those with trauma, increased the risk of SO developing. Trauma was 4 to 5 times as likely to induce SO than vitrectomy. The present findings will be valuable for counseling patients about the risks of SO after trauma and before performing intraocular surgeries.

Adoption of single agent anticancer therapy for advanced hepatocellular carcinoma and impact of facility type, insurance status, and income on survival: Analysis of the national cancer database 2004-2014.

BACKGROUND: This study analyzes the pattern of use of single agent anticancer therapy (SAACT) in the treatment and survival of advanced hepatocellular carcinoma (aHCC) before and after sorafenib was FDA approved in 2007. METHODS: Adult patients diagnosed with HCC and treated with only ACT from 2004 - 2014 were identified in NCDB database. Patients were analyzed during three time frames: 2004-2006 (pre-sorafenib (PS)), 2007-2010 (early sorafenib (ES)) and 2011-2014 (late sorafenib (LS)). Cox proportional hazards models and Kaplan-Meier method were used for analyses. RESULTS: The NCDB contained 31,107 patients with HCC diagnosed from 2004-2014 and treated with ACT alone. Patients were generally men (78.0%), >50 years of age (92.5%). A significant increase in the rate of adaption of SAACT was observed over time: 6.2% PS, 15.2% ES, and 22.2% LS (p < 0.0001). During this later period, the highest proportion of SAACT is among academic and integrated network facilities (23.3%) as compared to community facilities (17.0%, p < 0.0001). The median overall survival of patients with aHCC treated only with SAACT improved significantly over time from 8.0 months (m) (95% CI: 7.4-8.8) to 10.7 m (10.4-11.2) to 15.6 m (15.2-16.0, p < 0.001). Multivariate analysis indicates worse outcomes for patients treated at community cancer programs (HR 1.28, (5% CI: 1.23-1.32), patients without insurance (HR 1.11, 1.06-1.16) and estimated household income of <$63,000 (HR 1.09, 1.05-1.13). CONCLUSION: aHCC patients treated only with ACT have experienced an overall improvement in survival, but significant differences exist between facility type, insurance status, and income.

Characteristics of systematic reviews evaluating treatments for COVID-19 registered in PROSPERO.

Characteristics and research collaboration of registered systematic reviews (SRs) on treatment modalities for coronavirus disease-2019 (COVID-19) remain unclear. This study analysed research collaboration, interventions and outcome measures in registered SRs on COVID-19 treatments and pointed out the relevant problems. PROSPERO (international prospective register of systematic reviews) was searched for SRs on COVID-19 treatments as of 2 June 2020. Excel 2016 was used for descriptive analyses of the extracted data. VOSviewer 1.6.14 software was used to generate network maps for collaborations between countries and institutions. A total of 189 SRs were included, which were registered by 301 institutions from 39 countries. China (69, 36.50%) exhibited the highest output. Cooperation between countries was not close enough. As an institution, the Chengdu University of Traditional Chinese Medicine (7, 3.70%) had the highest output. There was close cooperation between institutions. Interventions included antiviral therapy (81, 42.86%), respiratory support (16, 8.47%), circulatory support (11, 5.82%), plasma therapy for convalescent patients (11, 5.82%), immunotherapy (9, 4.76%), TCM (traditional Chinese medicine) treatment (9, 4.76%), rehabilitation treatment (5, 2.65%), anti-inflammatory treatment (16, 8.47%) and other treatments (31, 16.40%). Concerning antiviral therapy (81, 42.86%), the most commonly used antiviral agents were chloroquine/hydroxychloroquine (26, 13.76%), followed by remdesivir (12, 6.35%), lobinavir/ritonavir (11, 5.82%), favipiravir (5, 2.65%), ribavirin (5, 2.65%), interferon (5, 2.65%), abiron (4, 2.12%) and abidor (4, 2.12%). The most frequently used primary and secondary outcomes were the mortality rate (92, 48.68%) and hospital stay length (48, 25.40%), respectively. The expression of the outcomes was not standardised. Many COVID-19 SRs on treatment modalities have been registered, with a low completion rate. Although there was some collaboration between countries and institutions in the currently registered SRs on treatment modalities for COVID-19 on PROSPERO, cooperation between countries should be further enhanced. More attention should be directed towards identifying deficiencies of outcome measures, and the standardisation of results should be maximised.

Recurrence Patterns After Surgical Resection of Gastroenteropancreatic Neuroendocrine Tumors: Analysis From the National Comprehensive Cancer Network Oncology Outcomes Database.

OBJECTIVE: Current National Comprehensive Cancer Network guidelines for gastroenteropancreatic neuroendocrine tumors (GEPNETs) recommend complete (R0) surgical resection of the primary tumor and metastases, if feasible. However, large multicenter studies of recurrence patterns of GEPNETs after resection have not been performed. METHODS: Patients 18 years or older who presented to 7 participating National Comprehensive Cancer Network institutions between 2004 and 2008 with a new diagnosis of a small bowel, pancreas, or colon/rectum neuroendocrine tumor (NET) and underwent R0 resection of the primary tumor, and synchronous metastases, if present, were included in this analysis. Descriptive statistics and Kaplan-Meier estimates were used to calculate recurrence rates and time-associated end points, respectively. RESULTS: Of 294 patients with GEPNETs, 50% were male, 88% were White, and 99% had Eastern Cooperative Oncology Group performance status 0 to 1. The median age was 55 years (range, 20-90). The median follow-up time from R0 resection was 62.1 months. Recurrence rates were 18% in small bowel NETs (n = 110), 26% in pancreatic NETs (n = 141), and 10% in colon/rectum NETs (n = 50). The frequency of surveillance imaging was highly variable. CONCLUSIONS: R0 resection was associated with variable risk of recurrence across subtypes. Further research to inform refinement of guidelines for the appropriate duration of surveillance after R0 resection is needed.

Inability of Radioiodine Remnant Ablation to Improve Postoperative Outcome in Adult Patients with Low-Risk Papillary Thyroid Carcinoma.

OBJECTIVE: To determine whether radioiodine remnant ablation (RRA) reduces cause-specific mortality (CSM) or tumor recurrence (TR) rate after bilateral lobar resection (BLR). PATIENTS AND METHODS: There were 2952 low-risk adult papillary thyroid cancer (LRAPTC) patients (with MACIS scores <6) who underwent potentially curative BLR during 1955-2014. During 1955-1974, 1975-1994, and 1995-2014, RRA was administered in 3%, 49%, and 28%. Statistical analyses were performed using SAS software. RESULTS: During 1955-1974, the 20-year CSM and TR rates after BLR alone were 1.0% and 6.8%; rates after BLR+RRA were 0% (P=.63) and 5.9% (P=.82). During 1975-1994, post-BLR 20-year rates for CSM and TR were 0.3% and 7.5%; after BLR+RRA, rates were higher at 0.9% (P=.31) and 12.8% (P=.01). When TR rates were examined separately for 448 node-negative and 317 node-positive patients, differences were nonsignificant. In 1995-2014, post-BLR 20-year CSM and TR rates were 0% and 9.2%; rates after BLR+RRA were higher at 1.4% (P=.19) and 21.0% (P<.001). In 890 pN0 cases, 15-year locoregional recurrence rates were 3.4% after BLR and 3.7% after BLR+RRA (P=.99). In 740 pN1 patients, 15-year locoregional recurrence rates were 10% higher after BLR+RRA compared with BLR alone (P=.01). However, this difference became nonsignificant when stratified by numbers of metastatic nodes. CONCLUSION: RRA administered to LRAPTC patients during 1955-2014 did not reduce either the CSM or TR rate. We would therefore not recommend RRA in LRAPTC patients undergoing BLR with curative intent.

Association of medicaid expansion of the Affordable Care Act with the stage at diagnosis and treatment of papillary thyroid cancer: A difference-in-differences analysis.

BACKGROUND: The Affordable Care Act's (ACA) Medicaid expansion has increased insurance coverage and improved various cancer outcomes. Its impact in papillary thyroid cancer (PTC) remains unclear. METHODS: Non-elderly patients (40-64 years-old) with PTC living in low-income areas either in a 2014 expansion, or a non-expansion state were identified from the National Cancer Database between 2010 and 2016. Insurance coverage, stage at diagnosis, and RAI administration were analyzed using a difference-in-differences analysis. RESULTS: 10,644 patients were included. Compared with non-expansion states, the percentage of uninsured patients (adjusted-DD -2.6% [95%-CI -4.3to-0.8%],p = 0.004) and patients with private insurance decreased, and those with Medicaid coverage increased (adjusted-DD 9.7% [95%-CI 6.9-12.5%],p < 0.001) in expansion states after ACA implementation. The percentage of patients with pT1 did not differ between expansion and non-expansion states; neither did the use of RAI. CONCLUSIONS: Medicaid expansion has resulted in a smaller uninsured population in PTC patients, but without earlier disease presentation nor change in RAI treatment.

Epidemiology and risk of psychiatric disorders among patients with celiac disease: A population-based national study.

BACKGROUND AND AIM: Celiac disease (CD) is a chronic disorder resulting from an immune reaction to gluten in genetically predisposed individuals. Although several studies have linked CD to psychiatric diseases, there are limited data on this topic. Using a large database, we sought to describe the epidemiology of several psychiatric disorders in CD. METHODS: We queried a multicenter database (Explorys Inc), an aggregate of electronic health record data from 26 major integrated healthcare systems from 2016 to 2020 consisting of 360 hospitals in the USA. A cohort of patients with a Systematized Nomenclature Of Medicine - Clinical Terms diagnosis of CD was identified. Multivariate analysis was performed using Statistical Package for Social Sciences version 25. RESULTS: Of the 37 465 810 patients in the database between 2016 and 2020, there were 112 340 (0.30%) individuals with CD. When compared with patients with no history of CD, patients with CD were more likely to have a history of anxiety (odds ratio [OR]: 1.385; 95% confidence interval [CI]: 1.364-1.407), depression (OR: 1.918; 95% CI: 1.888-1.947), bipolar (OR: 1.321; 95% CI: 1.289-1.354), attention-deficit hyperactivity disorder (OR: 1.753; 95% CI: 1.714-1.792), eating disorder (OR: 15.84; 95% CI: 15.533-16.154), and childhood autistic disorder (OR: 4.858; 95% CI: 3.626-6.508). Patients with CD and psychiatric conditions were more likely to be smokers, with history of alcohol and substance abuse as well as a history of personality disorder. CONCLUSIONS: In this large database, patients with CD are at increased risk of having multiple psychiatric diseases including anxiety, depression, bipolar, attention-deficit hyperactivity disorder, eating disorder, and childhood autism. Individual care and referral to psychiatry when appropriate are warranted while taking care of this group of patients.

Using local rather than general anesthesia for inguinal hernia repair may significantly reduce complications for frail Veterans.

BACKGROUND: Frailty predisposes patients to poor postoperative outcomes. We evaluated whether using local rather than general anesthesia for hernia repair could mitigate effects of frailty. METHODS: We used the Risk Analysis Index (RAI) to identify 8,038 frail patients in the 1998-2018 Veterans Affairs Surgical Quality Improvement Program database who underwent elective, open unilateral inguinal hernia repair under local or general anesthesia. Our outcome of interest was the incidence of postoperative complications. RESULTS: In total, 5,188 (65%) patients received general anesthesia and 2,850 (35%) received local. Local anesthesia was associated with a 48% reduction in complications (OR 0.52, 95%CI 0.38-0.72). Among the frailest patients (RAI≥70), predicted probability of a postoperative complication ranged from 22 to 33% with general anesthesia, compared to 13-21% with local. CONCLUSIONS: Local anesthesia was associated with a ∼50% reduction in postoperative complications in frail Veterans. Given the paucity of interventions for frail patients, there is an urgent need for a randomized trial comparing effects of anesthesia modality on postoperative complications in this vulnerable population.

Sex and Adverse Events of Adjuvant Chemotherapy in Colon Cancer: An Analysis of 34 640 Patients in the ACCENT Database.

BACKGROUND: Adjuvant chemotherapy is a standard treatment option for patients with stage III and high-risk stage II colon cancer. Sex is one of several factors responsible for the wide inter-patient variability in drug responses. Amalgamated data on the effect of sex on the toxicity of current standard adjuvant treatment for colorectal cancer are missing. METHODS: The objective of our study was to compare incidence and severity of major toxicities of fluoropyrimidine- (5FU or capecitabine) based adjuvant chemotherapy, with or without oxaliplatin, between male and female patients after curative surgery for colon cancer. Adult patients enrolled in 27 relevant randomized trials included in the ACCENT (Adjuvant Colon Cancer End Points) database, a large, multi-group, international data repository containing individual patient data, were included. Comparisons were conducted using logistic regression models (stratified by study and treatment arm) within each type of adjuvant chemotherapy (5FU, FOLFOX, capecitabine, CAPOX, and FOLFIRI). The following major toxicities were compared (grade III or IV and grade I-IV, according to National Cancer Institute Common Terminology Criteria [NCI-CTC] criteria, regardless of attribution): nausea, vomiting, nausea or vomiting, stomatitis, diarrhea, leukopenia, neutropenia, thrombocytopenia, anemia, and neuropathy (in patients treated with oxaliplatin). RESULTS: Data from 34 640 patients were analyzed. Statistically significant and clinically relevant differences in the occurrence of grade III or IV nonhematological {especially nausea (5FU: odds ratio [OR] = 2.33, 95% confidence interval [CI] = 1.90 to 2.87, P < .001; FOLFOX: OR = 2.34, 95% CI = 1.76 to 3.11, P < .001), vomiting (5FU: OR = 2.38, 95% CI = 1.86 to 3.04, P < .001; FOLFOX: OR = 2.00, 95% CI = 1.50 to 2.66, P < .001; CAPOX: OR = 2.32, 95% CI = 1.55 to 3.46, P < .001), and diarrhea (5FU: OR = 1.35, 95% CI = 1.21 to 1.51, P < .001; FOLFOX: OR = 1.60, 95% CI = 1.35 to 1.90, P < .001; FOLFIRI: OR = 1.57, 95% CI = 1.25 to 1.97, P < .001)} as well as hematological toxicities (neutropenia [5FU: OR = 1.55, 95% CI = 1.37 to 1.76, P < .001; FOLFOX: OR = 1.96, 95% CI = 1.71 to 2.25, P < .001; FOLFIRI: OR = 2.01, 95% CI = 1.66 to 2.43, P < .001; capecitabine: OR = 4.07, 95% CI = 1.84 to 8.99, P < .001] and leukopenia [5FU: OR = 1.74, 95% CI = 1.40 to 2.17, P < .001; FOLFIRI: OR = 1.75, 95% CI = 1.28 to 2.40, P < .001]) were observed, with women being consistently at increased risk. CONCLUSIONS: Our analysis confirms that women with colon cancer receiving adjuvant fluoropyrimidine-based chemotherapy are at increased risk of toxicity. Given the known sex differences in fluoropyrimidine pharmacokinetics, sex-specific dosing of fluoropyrimidines warrants further investigation.

Agreement of Risk-of -Bias varied in systematic reviews on acupuncture and was associated with methodological quality.

OBJECTIVES: The objective of the study was to evaluate the consistency of risk of bias assessments for overlapping randomized controlled trials (RCTs) included in systematic reviews (SRs) on acupuncture. STUDY DESIGN AND SETTING: Databases were searched for acupuncture SRs. A weighted kappa (κ) statistic was calculated, and logistic regression was used to explore the factors of disagreements. RESULTS: We included 241 RCTs from 109 SRs on acupuncture. The percentage disagreements ranged from 25% to 44%, with moderate agreement for random sequence generation (κ = 0.57), allocation concealment (κ = 0.50), and incomplete outcome data (κ = 0.50), besides fair agreement for blinding of participants and personnel (κ = 0.44), blinding of outcome assessment (κ = 0.31), and selective reporting (κ = 0.39). Only 19% RCTs were evaluated completely consistent. Methodological quality (random sequence generation, odds ratio (OR) = 3.46), international cooperation (allocation concealment, OR = 0.14; incomplete outcome data, OR = 0.14; selective reporting, OR = 0.05), and risk of bias reporting completeness score (selective reporting, OR = 0.53) significantly affected the relative odds of disagreements. CONCLUSION: The level of agreement varied from fair to moderate agreement depending on the risk of bias domain. Methodological quality appears to be an overarching factor to account for disagreements.

Major discrepancy between factual antibiotic resistance and consumption in South of France: analysis of 539,037 bacterial strains.

The burden of antibiotic resistance is currently estimated by mathematical modeling, without real count of resistance to key antibiotics. Here we report the real rate of resistance to key antibiotics in bacteria isolated from humans during a 5 years period in a large area in southeast in France. We conducted a retrospective study on antibiotic susceptibility of 539,107 clinical strains isolated from hospital and private laboratories in south of France area from January 2014 to January 2019. The resistance rate to key antibiotics as well as the proportion of bacteria classified as Difficult-to-Treat (DTR) were determined and compared with the Mann-Whitney U test, the χ2 test or the Fisher's exact test. Among 539,037 isolates, we did not observe any significant increase or decrease in resistance to key antibiotics for 5 years, (oxacillin resistance in Staphylococcus aureus, carbapenem resistance in enterobacteria and Pseudomonas aeruginosa and 3rd generation cephalosporin resistance in Escherichia coli and Klebsiella pneumoniae). However, we observed a significant decrease in imipenem resistance for Acinetobacter baumannii from 2014 to 2018 (24.19-12.27%; p = 0.005) and a significant increase of ceftriaxone resistance in Klebsiella pneumoniae (9.9-24.03%; p = 0.001) and Enterobacter cloacae (24.05-42.05%; p = 0.004). Of these 539,037 isolates, 1604 (0.3%) had a DTR phenotype. Over a 5-year period, we did not observe a burden of AR in our region despite a high rate of antibiotic consumption in our country. These results highlight the need for implementation of real-time AR surveillance systems which use factual data.

National pharmacological treatment trends for ankylosing spondylitis in South Korea: A national health insurance database study.

No studies of the current status of treatment options are available for ankylosing spondylitis (AS) patients in South Korea. This study assesses the current status of AS treatment trends using a nationwide database. This study was conducted using a Korean National Health Insurance System (KNHIS) dataset from 2006 to 2016. We randomly extracted 50% of the total number of patients registered as As patients in the KNHIS. The distribution of the number of patients according to age and gender was analyzed each year. The types and combination methods of drugs used during the study period were estimated yearly. Between 2006 and 2016, the number of AS patients increased linearly by an average of 9% annually, 6372 in 2006 to 15188 in 2016. The study found that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) was the most commonly prescribed pharmacological treatment option, followed by disease-modifying anti-rheumatic drugs (DMARDs) and then biologics. Biologics such as tumor necrosis factor alpha (TNF-α) inhibitors increased from 10% to 35% consistently for 10 years. In terms of combination therapy, DMARDs + NSAIDs accounted for almost 90% of treatments in 2006, but decreased by 65% in 2016. The use of biologics and NSAIDs increased from 3% to 28%. Prescriptions for dual therapies and mono therapies largely dominated prescription habits, accounted for up to approximately 80% of treatments. Among 10- to 14-year-old patients, there was no triple therapy, dual and triple therapies decreased gradually for those 60 and older, and the ratio of conservative treatments has increased. This study shows how South Korea reflects changes in AS treatment trends, along with the emergence of TNF-α inhibitors that are effective in treating AS. Research on clinical outcomes for AS treatments will be needed on following these drug changes.

Comparison of Three Different Data Sources of Adverse Drug Reactions Using Adverse Drug Reaction Data of Fluorouracil for Gastric Cancer as an Example.

Various sources of information are available for identifying and evaluating adverse drug reactions (ADRs). However, some studies only used the ADR data from spontaneous reporting databases to evaluate the safety of post-marketing drugs. This study was performed to identify an appropriate method for evaluating the safety of post-marketing drugs by comparing the frequencies of ADRs among three datasets: randomized controlled trials, published case reports, and spontaneous reports. Taking ADR data for fluorouracil as an example, we collected the three types of data and extracted their ADR information. All listed ADRs were sorted by frequency from high to low, and the top five ADRs were chosen from each dataset. We assigned an index value of 1.0 to the frequency of one specific ADR (diarrhea) and then calculated the index values of the other ADRs relative to diarrhea. Ten different ADRs were mentioned in the top five ADRs of the three datasets, and only diarrhea and nausea/vomiting were included in all three datasets. The rank orders of the top five ADRs varied among the three datasets. Nausea and vomiting was the most frequent ADR in all three datasets; the remaining ADRs differed among the datasets. There were significant differences in the recording of ADRs and the frequency distributions among the three datasets. A comprehensive and reliable safety profile for post-marketing drugs should not be based on any one source. Spontaneous reports from monitoring institutions provided the most ADR data. Randomized controlled trials and case reports published in the literature can supplement the results from spontaneous reports.

The Burden of Cervical Cancer in Korea: A Population-Based Study.

This study used the Korean National Health Insurance (NHI) claims database from 2011 to 2017 to estimate the incidence and the incidence-based cost of cervical cancer and carcinoma in situ of cervix uteri (CIS) in Korea. The primary outcome was the direct medical cost per patient not diagnosed with cervical cancer (C53) or CIS (D06) 2 years prior to the index date in the first year after diagnosis. A regression analysis was conducted to adjust for relevant covariates. The incidence of cervical cancer tended to decrease from 2013 to 2016, while that of CIS increased. In particular, the incidence rate of CIS in women in their 20 s and 30 s increased by 56.8% and 28.4%, respectively, from 2013 to 2016. The incidence-based cost of cervical cancer and CIS was USD 13,058 and USD 2695 in 2016, respectively, which increased from 2013. Multivariate regression analysis suggested that age was the most influential variable of the cost in both patient groups, and the cost was highest in those aged over 60, i.e., the medical cost was significantly lower in younger women than their older counterparts. These findings suggest that targeting younger women in cervical cancer prevention is a reasonable option from both economic and public health perspectives.

Characteristics of Clinical Trials relating to COVID-19 registered at ClinicalTrials.gov.

WHAT IS KNOWN AND OBJECTIVE: Since the beginning of the COVID-19 outbreak in China in December 2019, the epidemic has continued to spread globally. Despite continuous reports of clinical trials being launched, no studies have yet systematically summarized and analysed their characteristics. Our objective is to do this by reviewing trials registered at ClinicalTrials.gov. METHODS: We searched the ClinicalTrials.gov database and retrieved all clinical trials on COVID-19 registered up to and including 3 April 2020. We summarized the characteristics of the trials, presenting the results of all trials, all intervention trials and drug intervention (including vaccines and traditional Chinese medicine) trials. RESULTS AND DISCUSSION: We identified 306 COVID-19-related clinical trials. Seven of the studies had been withdrawn, leaving 299 active trials. Of the trials, 28.8% were planned to be conducted in Asia, 26.8% in Europe and 18.7% in North America. Most (73.0%) proposed trials expected to recruit fewer than 500 people, and only 22.1% of the studies included children (aged <18 years). About two-thirds (67.2%) of the studies were funded by the own resources of medical or research institutions. Of intervention trials, 73.9% used random allocation, and 73.4% used parallel assignment. Only 36.7% of the intervention trials used blinding. In terms of drug trials, 147 trials were drug intervention studies, covering 80 conventional drugs and seven traditional Chinese medicine drugs. Antiviral drugs and antimalarial drugs were the most commonly studied drugs with 52 and 45 trials registered, respectively. Five registered clinical trials were on vaccines. WHAT IS NEW AND CONCLUSION: A large number of COVID-19-related trials have been registered within the first 4 months since the first infection was reported. These involve a large number of different drugs, the most common being antiviral drugs and antimalarial drugs. More attention should be paid to adequate blinding in future trials.

Clinical management of tendinopathy: A systematic review of systematic reviews evaluating the effectiveness of tendinopathy treatments.

While the pathoetiology is disputed, a wide array of treatments is available to treat tendinopathy. The most common treatments found in the literature include therapeutic modalities, exercise protocols, and surgical interventions; however, their effectiveness remains ambiguous. The purpose of this study was to perform a systematic review of systematic reviews to determine the ability of therapeutic interventions to improve pain and dysfunction in patients with tendinopathy regardless of type or location. Five databases were searched for systematic reviews containing only randomized control trials to determine the effectiveness of treatments for tendinopathies based on pain and patient-reported outcomes. Systematic reviews were assessed via the Assessment of Multiple Systematic Reviews (AMSTAR) for methodological quality. From the database search, 3,295 articles were found, 107 passed the initial inclusion criteria. After further review, 25 systematic reviews were included in the final qualitative analysis. The AMSTAR scores were relatively high (8.8 ± 1.0) across the 25 systematic reviews. Eccentric exercises were the most common and consistently effective treatment for tendinopathy across systematic reviews. Low-level laser therapy and extracorporeal shockwave therapy demonstrated moderate effectiveness, while platelet-rich plasma injections demonstrated inconclusive evidence on their ability to decrease tendinopathy-related pain and improve function. Corticosteroids also showed some effectiveness for short-term pain, but for the long-term use deemed ineffective and at times contraindicated. Regarding surgical options, minimally invasive procedures were more effective compared to open surgical interventions. When treating tendinopathy regardless of location, eccentric exercises were the best treatment option to improve tendinopathy-related pain and improve self-reported function.

A scientometric analysis of neuroblastoma research.

BACKGROUND: Thousands of research articles on neuroblastoma have been published over the past few decades; however, the heterogeneity and variable quality of scholarly data may challenge scientists or clinicians to survey all of the available information. Hence, holistic measurement and analyzation of neuroblastoma-related literature with the help of sophisticated mathematical tools could provide deep insights into global research performance and the collaborative architectonical structure within the neuroblastoma scientific community. In this scientometric study, we aim to determine the extent of the scientific output related to neuroblastoma research between 1980 and 2018. METHODS: We applied novel scientometric tools, including Bibliometrix R package, biblioshiny, VOSviewer, and CiteSpace IV for comprehensive science mapping analysis of extensive bibliographic metadata, which was retrieved from the Web of ScienceTM Core Collection database. RESULTS: We demonstrate the enormous proliferation of neuroblastoma research during last the 38 years, including 12,435 documents published in 1828 academic journals by 36,908 authors from 86 different countries. These documents received a total of 316,017 citations with an average citation per document of 28.35 ± 7.7. We determine the proportion of highly cited and never cited papers, "occasional" and prolific authors and journals. Further, we show 12 (13.9%) of 86 countries were responsible for 80.4% of neuroblastoma-related research output. CONCLUSIONS: These findings are crucial for researchers, clinicians, journal editors, and others working in neuroblastoma research to understand the strengths and potential gaps in the current literature and to plan future investments in data collection and science policy. This first scientometric study of global neuroblastoma research performance provides valuable insight into the scientific landscape, co-authorship network architecture, international collaboration, and interaction within the neuroblastoma community.

Risk of Parkinson's disease in patients with hypothyroidism: A nationwide population-based cohort study.

INTRODUCTION: Hypothyroidism has been implicated in many other disease conditions, including neurodegenerative diseases. Parkinson's disease (PD) is one of the most common neurodegenerative diseases. The purpose of this study was to investigate the risk of PD in patients with hypothyroidism. METHODS: A total of 4725 patients with hypothyroidism and 4725 controls (without hypothyroidism) matched by age, gender, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 2000 and 2012. Patients were then followed until the end of 2013 using Taiwan's National Health Insurance Research Database, at which time participants who developed PD were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with a 95% confidence interval (CI) of PD incidence rate between patients with hypothyroidism and unaffected controls. RESULTS: Patients with hypothyroidism had a significantly increased risk of PD compared with unaffected controls (2.00 versus 1.10 per 1,000 person-years, HR: 1.77, 95% CI: 1.13-2.76) after adjusting for age, gender, CCI score, physical comorbidities (brain injury, cerebrovascular disease, hypertension, dyslipidemia, and diabetes mellitus), and duration of levothyroxine use. Also, older age (≥50 vs. <50 - HR:14.83), higher CCI score (CCI score 1-2 & ≥3 vs. 0 - HR: 1.66-1.74), and specific comorbidities (brain injury (HR: 1.78) and cerebrovascular disease (HR: 2.46)) significantly increased the risk of PD after adjusting for the variables mentioned above. CONCLUSIONS: Patients with hypothyroidism have an increased risk of developing PD. Other prospective studies that take into account genetic vulnerability and environmental exposures are warranted to confirm their relationship.

Benzodiazepine Use and Risk of Acute Angle-Closure Glaucoma: A Population-Based Case-Crossover Study.

INTRODUCTION: Theoretically, benzodiazepines (BZDs) can narrow the iridocorneal angle and induce acute angle-closure glaucoma (AACG). However, little evidence exists regarding this association. OBJECTIVE: The objective of this study was to assess whether the use of BZDs is associated with the risk of AACG. METHODS: We conducted a population-based case-crossover study using the nationwide claims database of the National Health Insurance Service in Korea. Patients with newly diagnosed AACG-between 1 January 2013 and 31 December 2016-who had received at least one BZD prescription prior to AACG diagnosis were enrolled. The date of AACG diagnosis was set as the index date. We assessed BZD use by each patient during a 30-day case period prior to the index date and three consecutive control periods that preceded this date. We used conditional logistic regression that adjusted for concomitant medications to determine the odds ratio for the use of BZDs in the case period compared with that in the control period in patients with incident AACG. RESULTS: Of the 11,093 patients with incident AACG, 6709 received a prescription for BZD prior to diagnosis. BZD use was associated with an increased risk of AACG [adjusted odds ratio (aOR) = 1.40; 95% confidence interval (CI) 1.27-1.54]. AACG risk was similar for short-acting (aOR = 1.40, 95% CI 1.24-1.57) and long-acting BZDs (aOR = 1.33, 95% CI 1.18-1.50). CONCLUSION: We found that BZD use was associated with AACG risk in the Korean population. Clinicians should carefully monitor the occurrence of visual disturbance in BZD-treated patients.