Effect of kinematics on the torque/force generation, surface characteristics, and shaping ability of a nickel-titanium rotary glide path instrument: An ex vivo study.

AIM: To evaluate the effect of various rotational motions on the torque/force generation, surface wear, and shaping ability of the ProGlider glide path instrument (Dentsply Sirona). METHODOLOGY: Mesiobuccal and mesiolingual canals of mandibular molars were selected based on the canal volume, length, angle of curvature (25°-40°), and radius of curvature (4-8 mm) after micro-computed tomographic scanning. The samples were randomly assigned to four groups (n = 13, each) according to movement kinematics [continuous rotation (CR; 300 rpm), optimum torque reverse motion (OTR; 180° forward and 90° reverse when torque >0.4 N cm), time-dependent reciprocal motion (TmR; 180° forward and 90° reverse), and optimal glide path motion (OGP; a combination of 90° forward, 90° reverse, 90° forward, and 120° reverse)]. Instrumentation was performed with an automated root canal instrument and torque/force analysing device. Maximum torque/force values, canal volume changes, and canal-centring ratios at 1, 3, 5, and 7 mm were evaluated. Surface defects (pits, grooves, microcracks, blunt cutting edges, and disruption of cutting edges) and spiral distortion on the ProGlider instrument were scored at the tip and 5 mm short of the tip before and after five consecutive uses with scanning electron microscopy. The Kruskal-Wallis test followed by Dunn's post-test with Bonferroni correction and Wilcoxon signed-rank test were used to analyse the data (α = 0.05). RESULTS: Optimal glide path motion generated significantly less clockwise torque and greater upward force than other groups (p < .05). OGP resulted in significantly fewer surface defects than CR (p < .05). In OGP and CR, the tip exhibited more surface defects than 5 mm short of the tip (p < .05). CR resulted in greater volume changes than OGP and TmR (p < .05) and greater centring ratios (i.e., more deviation) than OGP at 1 mm and OTR at 3 mm (p < .05). CONCLUSIONS: Under laboratory conditions using the ProGlider instrument, OGP generated significantly less clockwise torque and greater upward force than the other rotatory motions. OGP generated fewer superficial defects than CR, and the three modes of reciprocal rotation better maintained the apical curvature of root canals than CR with the ProGlider instrument.

Effect of different axial speed patterns on cyclic fatigue resistance of rotary nickel-titanium instruments.

BACKGROUND: To evaluate the effect of pecking motions with faster upward speed on the dynamic cyclic fatigue resistance of nickel-titanium rotary instruments with different metallurgy. METHODS: Forty each of ProTaper Universal F3 (PTU) and ProTaper Gold F3 (PTG) instruments (size #30/.09) were equally divided into four groups. The test was performed using an 18-mm-long stainless steel artificial canal with a 5-mm radius of curvature, a 45° canal curvature and a 2-mm canal diameter. A downward speed of 100 mm/min was employed, while the upward speed was set at 100, 150, 200 or 300 mm/min. Time to failure (Tf), number of cycles to failure (Nf) and number of pecking motions to failure (Np) were recorded. Statistical analysis was performed using Kruskal Wallis and Mann-Whitney U tests for Tf, Nf, and Np (α = 0.05). RESULTS: The 100/300 mm/min group showed significantly higher Np values than the 100/100 mm/min group (p < 0.05), whereas there were no significant differences in Tf and Nf among the tested speed groups (p < 0.05) in either PTU or PTG. PTG exhibited significantly higher Tf, Nf, and Np than PTU (p < 0.05). CONCLUSIONS: Under the tested conditions, the fastest upward speed group showed significantly higher cyclic fatigue resistance, as demonstrated by larger Np, than the same speed group. PTG had significantly higher cyclic fatigue resistance than PTU in all groups.

Prevalence and risk factors for sessile serrated lesions in an average risk colorectal cancer screening population.

BACKGROUND AND AIM: The reported prevalence and risk factors for sessile serrated lesions (SSLs) show significant variation. We aimed to specifically study the prevalence and potential risk factors of SSLs in an average risk colorectal cancer (CRC) screening population of Chinese subjects. METHODS: This is a case-control study of prospectively collected data from a territory-wide colorectal screening program in Hong Kong. Information on risk factors was obtained from questionnaires completed prior to screening colonoscopy. We compared subjects with SSLs against controls without these lesions to identify potential risk factors using multivariable logistic regression. RESULTS: Of 12 039 asymptomatic screening subjects, 6011 subjects received a screening colonoscopy with 2214 subjects (36.8%) having conventional adenomas, 486 subjects (8.1%) having hyperplastic polyps, and 85 subjects (1.4%) having SSLs only. Of these subjects, three had synchronous advanced adenomas and were excluded from the analysis. More than 60% of these lesions were in the proximal colon. We compared these 82 subjects with SSLs only and 3226 controls without any polyps. After multivariable logistic regression, age ≥ 66 years, smoking, and diabetes mellitus (DM) were significant independent risk factors for SSLs. CONCLUSION: In this study, we report the prevalence of SSLs to be 1.4%. Age ≥ 66 years, smoking, and DM were independent risk factors for these lesions. Our findings provide relevant new data that should be taken into consideration when designing region-specific surveillance programs for SSLs with the ultimate goal of reducing the risk of CRC.

Cost of Respiratory Syncytial Virus-Associated Acute Lower Respiratory Infection Management in Young Children at the Regional and Global Level: A Systematic Review and Meta-Analysis.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infection (ALRI) in young children aged <5 years. METHODS: We aimed to identify the global inpatient and outpatient cost of management of RSV-ALRI in young children to assist health policy makers in making decisions related to resource allocation for interventions to reduce severe morbidity and mortality from RSV in this age group. We searched 3 electronic databases including Global Health, Medline, and EMBASE for studies reporting cost data on RSV management in children under 60 months from 2000 to 2017. Unpublished data on the management cost of RSV episodes were collected through collaboration with an international working group (RSV GEN) and claim databases. RESULTS: We identified 41 studies reporting data from year 1987 to 2017, mainly from Europe, North America, and Australia, covering the management of a total of 365 828 RSV disease episodes. The average cost per episode was €3452 (95% confidence interval [CI], 3265-3639) and €299 (95% CI, 295-303) for inpatient and outpatient management without follow-up, and it increased to €8591(95% CI, 8489-8692) and €2191 (95% CI, 2190-2192), respectively, with follow-up to 2 years after the initial event. CONCLUSIONS: Known risk factors (early and late preterm birth, congenital heart disease, chronic lung disease, intensive care unit admission, and ventilator use) were associated with €4160 (95% CI, 3237-5082) increased cost of hospitalization. The global cost of inpatient and outpatient RSV ALRI management in young children in 2017 was estimated to be approximately €4.82 billion (95% CI, 3.47-7.93), 65% of these in developing countries and 55% of global costs accounted for by hospitalization. We have demonstrated that RSV imposed a substantial economic burden on health systems, governments, and the society.

Prospective colonoscopic study to investigate risk of colorectal neoplasms in first-degree relatives of patients with non-advanced adenomas.

OBJECTIVE: The risk associated with a family history of non-advanced adenoma (non-AA) is unknown. We determined the prevalence of colorectal neoplasms in subjects who have a first-degree relative (FDR) with non-AA compared with subjects who do not have an FDR with adenomas. DESIGN: In a blinded, cross-sectional study, consecutive subjects with newly diagnosed non-AA were identified from our colonoscopy database. 414 FDRs of subjects with non-AA (known as exposed FDRs; mean age 55.0±8.1 years) and 414 age and sex-matched FDRs of subjects with normal findings from colonoscopy (known as unexposed FDRs; mean age 55.2±7.8 years) underwent a colonoscopy from November 2015 to June 2018. One FDR per family was recruited. FDRs with a family history of colorectal cancer were excluded. The primary outcome was prevalence of advanced adenoma (AA). Secondary outcomes included prevalence of all adenomas and cancer. RESULTS: The prevalence of AA was 3.9% in exposed FDRs and 2.4% in unexposed FDRs (matched OR (mOR)=1.67; 95% CI 0.72 to 3.91; p=0.238 adjusted for proband sex and proband age). Exposed FDRs had a higher prevalence of any adenomas (29.2% vs 18.6%; mOR=1.87; 95% CI 1.32 to 2.66; p<0.001) and non-AA (25.4% vs 16.2%; mOR=1.91; 95% CI 1.32 to 2.76; p=0.001). A higher proportion of exposed FDRs than unexposed FDRs (4.3% vs 2.2%; adjusted mOR=2.44; 95% CI 1.01 to 5.86; p=0.047) had multiple adenomas. No cancer was detected in both groups. CONCLUSION: A positive family history of non-AA does not significantly increase the risk of clinically important colorectal neoplasia. The data support current guidelines which do not advocate earlier screening in individuals with a family history of non-AA. TRIAL REGISTRATION NUMBER: NCT0252172.

Risk of Postpolypectomy Bleeding With Uninterrupted Clopidogrel Therapy in an Industry-Independent, Double-Blind, Randomized Trial.

BACKGROUND & AIMS: Guidelines recommend withholding clopidogrel 7 days before polypectomy to decrease bleeding risk, but these were written based on limited evidence. We investigated whether uninterrupted clopidogrel therapy increases the risk of delayed postpolypectomy bleeding in patients undergoing colonoscopy. METHODS: We identified patients receiving clopidogrel for cardiovascular disease undergoing elective colonoscopies in Hong Kong from February 28, 2012 through April 11, 2018. Eligible patients were instructed to stop taking clopidogrel 7 days before colonoscopy. Then, they were randomly assigned to groups given clopidogrel (75 mg) or placebo daily until the morning of colonoscopy. All patients resumed their usual prescriptions of clopidogrel after colonoscopy. The primary end point was delayed postpolypectomy bleeding that required hospitalization or intervention up to 30 days after colonoscopy. Secondary end points were immediate postpolypectomy bleeding and serious cardio-thrombotic events for as long as 6 months after colonoscopy, according to Antithrombotic Trialists' criteria. All events were adjudicated by an independent masked committee. RESULTS: In total, 387 patients underwent colonoscopy and 216 required polypectomies (106 patients in the clopidogrel group and 110 patients in the placebo group). The cumulative incidence of delayed postpolypectomy bleeding was 3.8% (95% confidence interval 1.4-9.7) in the clopidogrel group and 3.6% (95% confidence interval 1.4-9.4) in the placebo group (P = .945 by log-rank test). There were no significant differences in immediate postpolypectomy bleeding (8.5% vs 5.5%; P = .380) and cardio-thrombotic events (1.5% vs 2%; P = .713). CONCLUSIONS: In a randomized controlled trial of clopidogrel users undergoing colonoscopy, a slightly larger proportion of patients continuing clopidogrel developed delayed and immediate postpolypectomy bleeding, although this difference was not statistically significant. ClinicalTrials.gov, number NCT01806090.

Endoscopic ultrasound-guided cyanoacrylate injection to prevent rebleeding in hepatocellular carcinoma patients with variceal hemorrhage.

BACKGROUND AND AIM: Secondary prophylaxis (SP) of variceal rebleeding was reported to improve outcomes of hepatocellular carcinoma (HCC) patients, but the optimal endoscopic approach is not well defined. We compared outcomes in HCC patients who underwent SP by endoscopic ultrasound-guided cyanoacrylate obturation (EUS-CYA) versus no SP. METHODS: Between 2014 and 2018, 30 consecutive patients with inoperable HCC and recent endoscopically controlled variceal bleeding were prospectively recruited. Twenty-seven patients with persistent varices ≥ 3 mm on endoscopic ultrasound underwent EUS-CYA for SP. Thirty-three HCC patients treated by esophagogastroduodenoscopy-guided CYA obturation (EGD-CYA) alone for acute variceal bleeding between 2009 and 2013 were identified from a prospective gastrointestinal bleed registry as standard of care controls for comparison. Outcome measures were death-adjusted cumulative incidence of rebleeding, bleeding-free survival, technical success, and procedure-related adverse events of EUS-CYA. RESULTS: The majority of patients in both groups had advanced HCC, portal vein thrombosis, and Child-Pugh B cirrhosis. EUS-CYA was successful in all 27 patients with no radiographic evidence of cyanoacrylate-lipiodol embolization. Significantly lower 30- and 90-day death-adjusted cumulative incidence of rebleeding (14.8% vs 42.4%, P = 0.023 and 18.5% vs 60.6%, P = 0.002, respectively) and significantly higher variceal bleeding-free survival at 3 and 6 months (51.9% vs 21.2%, P = 0.009, 40.7% vs 15.2%, P = 0.010, respectively) were observed in the EUS-CYA group when compared with standard of care group. CONCLUSIONS: Secondary prophylaxis by EUS-CYA reduced rebleeding rate and improved variceal bleeding-free survival in patients with inoperable HCC and variceal bleeding when compared with no SP. Randomized studies are needed to confirm the benefits of EUS-CYA for this difficult-to-treat population.

Changes in Otitis Media Episodes and Pressure Equalization Tube Insertions Among Young Children Following Introduction of the 13-Valent Pneumococcal Conjugate Vaccine: A Birth Cohort-based Study.

BACKGROUND: The impact of 13-valent pneumococcal conjugate vaccine (PCV13) introduction on the occurrence of first and subsequent otitis media (OM) episodes in early childhood is unclear. We compared the risk of OM episodes among children age <2 years before and after PCV13 introduction, accounting for the dependence between OM episodes. METHODS: We identified consecutive annual (July-June) cohorts of Tennessee Medicaid-enrolled children (2006-2014) from birth through age 2 years. We identified OM episodes using coded diagnoses (we classified diagnoses <21 days apart as the same episode). We modeled adjusted hazard ratios (aHRs) for OM comparing 7-valent pneumococcal conjugate vaccine (PCV7)-era (2006-2010) and PCV13-era (2011-2014) birth cohorts, accounting for risk factors and dependence between first and subsequent episodes. Secondary analyses examined pressure equalization tube (PET) insertions and compared the risk of recurrent OM (≥3 episodes in 6 months or ≥4 episodes in 12 months) between PCV7- and PCV13-era birth cohorts. RESULTS: We observed 618 968 OM episodes and 24 875 PET insertions among 368 063 children. OM and PET insertion rates increased during the PCV7 years and declined after PCV13 introduction. OM and PET insertion risks were lower in the 2013-2014 cohort compared with the 2009-2010 cohort (aHRs [95% confidence interval], 0.92 [.91-.93] and 0.76 [.72-.80], respectively). PCV13 introduction was associated with declines in the risk of first, subsequent, and recurrent OM. CONCLUSIONS: The transition from PCV7 to PCV13 was associated with a decline of OM among children aged <2 years due to a reduction in the risk of both the first and subsequent OM episodes.

Misoprostol Heals Small Bowel Ulcers in Aspirin Users With Small Bowel Bleeding.

BACKGROUND & AIMS: There is no effective treatment for aspirin-induced small bowel ulcer bleeding. We performed a double-blind, randomized, placebo-controlled trial to determine whether misoprostol can heal small bowel ulcers in patients with small bowel bleeding who require continuous aspirin therapy. METHODS: We performed a prospective study of 84 aspirin users with small bowel bleeding who required continued aspirin therapy in Hong Kong and Japan. Patients with small bowel ulcers or multiple erosions, detected by capsule endoscopy, were randomly assigned to groups that received either misoprostol (200 µg, 4 times daily; n = 42) or placebo (n = 42) for 8 weeks. All patients continued taking aspirin (100 mg, once daily). The primary end point was complete ulcer healing at follow-up capsule endoscopy. Secondary end points included changes in hemoglobin level and number of ulcer/erosions from baseline. RESULTS: Complete healing of small bowel ulcers was observed in 12 patients in the misoprostol group (28.6%; 95% CI, 14.9%-42.2%) and 4 patients in the placebo group (9.5%; 95% CI, 0.6%-18.4%), for a difference in proportion of 19.0% (95% CI, 2.8%-35.3%; P = .026). The misoprostol group had a significantly greater mean increase in hemoglobin than the placebo group (mean difference, 0.70 mg/dL; 95% CI, 0.05-1.36; P = .035). The reduction in medium number of ulcers or erosions was significantly greater in the misoprostol group (from 6.5 [range, 1-85] to 2 [range, 0-25]) than in the placebo group (from 7 [range, 1-29] to 4 [range, 0-19] (P = .005). CONCLUSIONS: In a double-blind, randomized, placebo-controlled trial, we found misoprostol to be superior to placebo in promoting healing of small bowel ulcers among aspirin users complicated by small bowel ulcer bleeding who require continuous aspirin therapy. However, use of misoprostol alone would provide only limited protection against aspirin on the small bowel. ClinicalTrials.gov ID NCT01998776.

Increasing Trend in Young-Onset Colorectal Cancer in Asia: More Cancers in Men and More Rectal Cancers.

BACKGROUND: The incidence of young-onset colorectal cancer (CRC) is reported to be increasing in the Western world. There are no population-based studies assessing the trend across Asia. METHODS: We performed a multinational cohort study involving four Asian countries/regions, namely Taiwan, Korea, Japan, and Hong Kong. The magnitude and direction of trend in the incidence of young-onset CRC (age < 50) were quantified using Joinpoint Regression Program to estimate average annual percentage change (AAPC). RESULTS: In Taiwan (1995-2014), incidence of young-onset CRC significantly increased in both men (colon cancer: 4.9-9.7 per 100,000; rectal cancer: 4.0-8.3 per 100,000) and women (colon cancer: 5.1-9.7 per 100,000; rectal cancer: 3.8-6.4 per 100,000). In Korea (1999-2014), incidence of young-onset CRC significantly increased in both men (colon cancer: 5.0-10.4 per 100,000; rectal cancer: 4.9-14.0 per 100,000) and women (colon cancer: 4.1-9.6 per 100,000; rectal cancer: 4.1-9.1 per 100,000). The most pronounced change was observed with male rectal cancer, increasing by 3.9% per year in Taiwan (AAPC + 3.9, 95% confidence interval + 3.3 to +4.5, P < 0.05) and 6.0% per year in Korea (AAPC +6.0, 95% confidence interval + 4.5 to +7.6, P < 0.05). Only a significant increase in rectal cancer was noted in Japan (male rectal cancer: 7.2-10.1 per 100,000, female rectal cancer 4.7-6.7 per 100,000) and Hong Kong (male rectal cancer: 4.4-7.0 per 100,000). CONCLUSIONS: Increasing trend in young-onset CRC is not limited to the Western world. This finding may have implications on screening program for CRC in these countries/regions.

Gastrointestinal safety of celecoxib versus naproxen in patients with cardiothrombotic diseases and arthritis after upper gastrointestinal bleeding (CONCERN): an industry-independent, double-blind, double-dummy, randomised trial.

BACKGROUND: Present guidelines are conflicting for patients at high risk of both cardiovascular and gastrointestinal events who continue to require non-steroidal anti-inflammatory drugs (NSAIDs). We hypothesised that a cyclooxygenase-2-selective NSAID plus proton-pump inhibitor is superior to a non-selective NSAID plus proton-pump inhibitor for prevention of recurrent ulcer bleeding in concomitant users of aspirin with previous ulcer bleeding. METHODS: For this industry-independent, double-blind, double-dummy, randomised trial done in one academic hospital in Hong Kong, we screened patients with arthritis and cardiothrombotic diseases who were presenting with upper gastrointestinal bleeding, were on NSAIDs, and require concomitant aspirin. After ulcer healing, an independent staff member randomly assigned (1:1) patients who were negative for Helicobacter pylori with a computer-generated list of random numbers to receive oral administrations of either celecoxib 100 mg twice per day plus esomeprazole 20 mg once per day or naproxen 500 mg twice per day plus esomeprazole 20 mg once per day for 18 months. All patients resumed aspirin 80 mg once per day. Both patients and investigators were masked to their treatments. The primary endpoint was recurrent upper gastrointestinal bleeding within 18 months. The primary endpoint and secondary safety endpoints were analysed in the modified intention-to-treat population. This study was registered with ClinicalTrials.gov, number NCT00153660. FINDINGS: Between May 24, 2005, and Nov 28, 2012, we enrolled 514 patients, assigning 257 patients to each study group, all of whom were included in the intention-to-treat population. Recurrent upper gastrointestinal bleeding occurred in 14 patients in the celecoxib group (nine gastric ulcers and five duodenal ulcers) and 31 patients in the naproxen group (25 gastric ulcers, three duodenal ulcers, one gastric ulcer and duodenal ulcer, and two bleeding erosions). The cumulative incidence of recurrent bleeding in 18 months was 5·6% (95% CI 3·3-9·2) in the celecoxib group and 12·3% (8·8-17·1) in the naproxen group (p=0·008; crude hazard ratio 0·44, 95% CI 0·23-0·82; p=0·010). Excluding patients who reached study endpoints, 21 (8%) patients in the celecoxib group and 17 (7%) patients in the naproxen group had adverse events leading to discontinuation of treatment. No treatment-related deaths occurred during the study. INTERPRETATION: In patients at high risk of both cardiovascular and gastrointestinal events who require concomitant aspirin and NSAID, celecoxib plus proton-pump inhibitor is the preferred treatment to reduce the risk of recurrent upper gastrointestinal bleeding. Naproxen should be avoided despite its perceived cardiovascular safety. FUNDING: The Research Grant Council of Hong Kong.

Similar Efficacy of Proton-Pump Inhibitors vs H2-Receptor Antagonists in Reducing Risk of Upper Gastrointestinal Bleeding or Ulcers in High-Risk Users of Low-Dose Aspirin.

BACKGROUND & AIMS: It is not clear whether H2-receptor antagonists (H2RAs) reduce the risk of gastrointestinal (GI) bleeding in aspirin users at high risk. We performed a double-blind randomized trial to compare the effects of a proton pump inhibitor (PPI) vs a H2RA antagonist in preventing recurrent upper GI bleeding and ulcers in high-risk aspirin users. METHODS: We studied 270 users of low-dose aspirin (≤325 mg/day) with a history of endoscopically confirmed ulcer bleeding at 8 sites in Hong Kong and Japan. After healing of ulcers, subjects with negative results from tests for Helicobacter pylori resumed aspirin (80 mg) daily and were assigned randomly to groups given a once-daily PPI (rabeprazole, 20 mg; n = 138) or H2RA (famotidine, 40 mg; n = 132) for up to 12 months. Subjects were evaluated every 2 months; endoscopy was repeated if they developed symptoms of upper GI bleeding or had a reduction in hemoglobin level greater than 2 g/dL and after 12 months of follow-up evaluation. The adequacy of upper GI protection was assessed by end points of recurrent upper GI bleeding and a composite of recurrent upper GI bleeding or recurrent endoscopic ulcers at month 12. RESULTS: During the 12-month study period, upper GI bleeding recurred in 1 patient receiving rabeprazole (0.7%; 95% confidence interval [CI], 0.1%-5.1%) and in 4 patients receiving famotidine (3.1%; 95% CI, 1.2%-8.1%) (P = .16). The composite end point of recurrent bleeding or endoscopic ulcers at month 12 was reached by 9 patients receiving rabeprazole (7.9%; 95% CI, 4.2%-14.7%) and 13 patients receiving famotidine (12.4%; 95% CI, 7.4%-20.4%) (P = .26). CONCLUSIONS: In a randomized controlled trial of users of low-dose aspirin at risk for recurrent GI bleeding, a slightly lower proportion of patients receiving a PPI along with aspirin developed recurrent bleeding or ulcer than of patients receiving an H2RA with the aspirin, although this difference was not statistically significant. ClincialTrials.gov no: NCT01408186.

Trends in healthcare utilization and costs associated with pneumonia in the United States during 2008-2014.

BACKGROUND: Pneumonia is the leading cause of morbidity and mortality worldwide. Pneumococcal conjugate vaccines have reduced the burden of pneumonia, but data on the current burden of pneumonia and its impact on the healthcare system are needed to inform the development and use of new vaccines and other preventive measures. METHODS: We retrospectively analyzed the frequency of pneumonia in the US during 2008-2014 using data from the MarketScan® Commercial Claims and Encounters database. Frequencies of healthcare utilization related to the index pneumonia episode were calculated using the annual number of enrolled person-years (PY) as the denominator and the number of individuals with pneumonia as the numerator. Pneumonia-associated costs were calculated as mean payment per episode during the 2 years from 2013 to 2014. RESULTS: The overall annual healthcare utilization rate for pneumonia was 15.1 per 1000 PY and decreased slightly from 2008 to 2014 (from 15.4 to 13.5 per 1000 PY). Most pneumonia-related healthcare utilization was due to office/outpatient visits (10.3 per 1000 PY; 68.3%). Emergency department/urgent care visits (2.5 per 1000 PY; 16.9%) and hospitalizations (2.2 per 1000 PY; 14.8%) contributed less. Pneumonia-related healthcare utilization was highest in children < 5 years (rate per 1000 PY = 29.7 for < 1 year, 47.9 for 1 year, and 39.5 for 2-4 years) and adults > 65 years (45.0 per 1000 PY). The mean cost per pneumonia episode (95% confidence interval) was US$429.1 ($424.8-$433.4) for office/outpatient visits, $1126.9 ($1119.5-$1134.3) for emergency department/urgent care visits, and $10,962.5 ($10,822.8-$11,102.2) for hospitalization. CONCLUSIONS: The burden of pneumonia on the US healthcare system remains substantial. The results presented here can help guide new vaccination strategies and other preventive interventions for reducing the remaining burden of pneumonia.

Healthcare resource use and economic burden attributable to respiratory syncytial virus in the United States: a claims database analysis.

BACKGROUND: Despite several studies that have estimated the economic impact of Respiratory Syncytial Virus (RSV) in infants, limited data are available on healthcare resource use and costs attributable to RSV across age groups. The aim of this study was to quantify age-specific RSV-related healthcare resource use and costs on the US healthcare system. METHODS: This retrospective case-control study identified patients aged ≥1 year with an RSV event in the Truven Health Marketscan® Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases between August 31, 2012 and August 1, 2013. RSV patients were matched 1:1 with non-RSV controls for age, gender, region, healthcare plan and index date (n = 11,432 in each group). Stratified analyses for healthcare resource use and costs were conducted by age groups. RSV-attributable resource use and costs were assessed based on the incremental differences between RSV cases and controls using multivariate analysis. RESULTS: RSV patients had a higher healthcare resource use (hospital stays, emergency room/urgent care visits, ambulatory visits and outpatient visits) than non-RSV matched controls for all age groups (all p < 0.0001), particularly in the elderly age groups with RSV (1.9 to 3 days length of stay, 0.4 to 0.5 more ER/UC visits, 0.7 to 2.7 more ambulatory visits, 12.1 to 18.6 more outpatient visits and 9.5 to 14.6 more prescriptions than elderly in the control groups). The incremental difference in adjusted mean annual costs between RSV and non-RSV controls was higher in elderly (≥65; $12,030 to $23,194) than in those aged < 65 years ($2251 to $5391). Among children, adjusted costs attributable to RSV were higher in children aged 5-17 years ($3192), than those 1-4 years ($2251 to $2521). CONCLUSIONS: Our findings showed a substantial annual RSV-attributable healthcare resource use and costs in the US across age groups, with the highest burden in those aged ≥65 years. These data can be used in cost-effectiveness analyses, and may be useful for policymakers to guide future RSV vaccination and other prevention programs.

Trends in healthcare utilization and costs associated with acute otitis media in the United States during 2008-2014.

BACKGROUND: Acute otitis media (AOM) is the most common cause of pediatric medical visits and antibiotic prescriptions worldwide, but its current impact on the US healthcare system is not clear. The aim of this study was to investigate changes in the incidence of AOM from 2008, just before 13-valent pneumococcal conjugate vaccine was introduced, to 2014 using US insurance records in the Truven MarketScan® database. The study also examined the costs associated with index AOM events during the two most recent years for which data were available (2013-2014). METHODS: AOM cases in the MarketScan database during 2008-2014 were identified using ICD9 diagnosis codes 381.xx and 382.xx. Incidence rates of healthcare utilization related to the index AOM episode were calculated using the annual number of enrolled person-years as the denominator and the number of individuals with AOM as the numerator. AOM-associated costs were calculated as the mean payment per episode during the 2 years from 2013 to 2014. RESULTS: The overall annual rate of AOM-related healthcare utilization was 60.5 per 1000 person-years and changed little from 2008 to 2014 (range, 58.4-62.6). Most of this was due to office/outpatient visits (55.7 [range, 52.0-58.8] per 1000 person-years). Emergency department/urgent care visits (4.7 [range 3.7-6.3] per 1000 person-years) and hospitalization (0.0 [range, 0.0-0.1] per 1000 person-years) contributed little. The rate of AOM-related healthcare utilization per 1000 person-years was highest in the youngest children and declined with age (474.3 for < 1 year, 503.9 for 1 year, 316.3 for 2-4 years, 94.9 for 5-17 years, 33.1 for 18-49 years, 28.6 for 50-64 years, 23.7 for 65-74 years, 20.2 for 75-84 years, and 16.1 for ≥85 years). The mean cost per AOM episode in 2013-2014 (95% confidence interval) was $199.0 (198.4-199.6) for office or outpatient visits, $329.6 (328.2-331.0) for emergency department/urgent care visits, and $1592.9 (1422.0-1763.8) for hospitalization. CONCLUSIONS: In the US, AOM-associated healthcare utilization and costs remain substantial. More effective preventive measures such as new vaccines are needed to reduce the burden of AOM.

A prospective study on second-generation colon capsule endoscopy to detect mucosal lesions and disease activity in ulcerative colitis (with video).

BACKGROUND AND AIMS: Mucosal healing is the goal for ulcerative colitis (UC) therapy, but it needs to be confirmed via colonoscopy. Colon capsule endoscopy (CCE) is a noninvasive technique for colon investigation. Our study investigated the accuracy of second-generation CCE (CCE-2) in assessing mucosal lesions and disease activity in UC. METHODS: In this prospective study, CCE-2 and conventional colonoscopy were performed on the same day. CCE-2 reviewers and colonoscopists used the Mayo endoscopic subscore (MES) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) to assess disease activity, and they were blinded to each other's findings. Diagnostic parameters of CCE-2 for identifying mucosal lesions were evaluated by using colonoscopy as the reference. RESULTS: A total of 150 patients were enrolled. Of the 150 patients, 108 were included for per-patient analysis. CCE-2 and colonoscopy showed substantial agreement in measuring MES (intraclass correlation coefficient [ICC] 0.69; 95% confidence interval [CI], 0.46-0.81; P < .001) and UCEIS (ICC 0.64; 95% CI, 0.38-0.78; P < .001). CCE-2 had a sensitivity of 97% and 94% to detect mucosal inflammation (MES >0) and moderate to severe inflammation (MES >1), respectively. In per-segment analysis, the negative predictive values of CCE-2 to detect mucosal inflammation, including vascular pattern loss, bleeding, and erosions reached 94% to 95%. Interobserver agreement between 2 independent CCE-2 readers for both scoring systems was good (ICC > .80). The sensitivity and specificity of CCE-2 in detecting postinflammatory polyps were 100% and 91%, respectively. CCE-2 was better tolerated and preferred by patients than was colonoscopy. CONCLUSIONS: CCE-2 yields high accuracy in detecting mucosal lesions and determining disease severity in UC. It represents a well-tolerated and reliable tool for disease monitoring in UC. (Clinical trial registration number: NCT02469103.).

Clinical Features of Influenza and Acute Respiratory Illness in Older Adults at Least 50 Years of Age in an Outpatient Setting in the Republic of Korea: a Prospective, Observational, Cohort Study.

Two prospective, multi-centre, observational studies (GlaxoSmithKline [GSK] identifier No. 110938 and 112519) were performed over 2 influenza seasons (2007-2008 and 2008-2009) in the Republic of Korea (ROK) with the aim to evaluate the burden of laboratory-confirmed influenza (LCI) in patients ≥ 50 years of age seeking medical attention for acute respiratory illness (ARI). The median participant age was 58 years in the 2007-2008 season and 60 years in the 2008-2009 season. LCI was observed in 101/346 (29.2%) of ARI patients in the 2007-2008 season and in 166/443 (37.5%) of ARI patients in the 2008-2009 season. Compared to patients with non-influenza ARI, those with LCI had higher rates of decreased daily activities (60.4% vs. 32.9% in 2007-2008 and 46.4% vs. 25.8% in 2008-2009), work absenteeism (51.1% vs. 25.6% and 14.4% vs. 7.7%), and longer duration of illness. These results indicated that influenza is an important cause of ARI in adults aged 50 and older causing more severe illness than non-influenza related ARI.

Cost of hospital management of Clostridium difficile infection in United States-a meta-analysis and modelling study.

BACKGROUND: Clostridium difficile infection (CDI) is the leading cause of infectious nosocomial diarrhoea but the economic costs of CDI on healthcare systems in the US remain uncertain. METHODS: We conducted a systematic search for published studies investigating the direct medical cost associated with CDI hospital management in the past 10 years (2005-2015) and included 42 studies to the final data analysis to estimate the financial impact of CDI in the US. We also conducted a meta-analysis of all costs using Monte Carlo simulation. RESULTS: The average cost for CDI case management and average CDI-attributable costs per case were $42,316 (90 % CI: $39,886, $44,765) and $21,448 (90 % CI: $21,152, $21,744) in 2015 US dollars. Hospital-onset CDI-attributable cost per case was $34,157 (90 % CI: $33,134, $35,180), which was 1.5 times the cost of community-onset CDI ($20,095 [90 % CI: $4991, $35,204]). The average and incremental length of stay (LOS) for CDI inpatient treatment were 11.1 (90 % CI: 8.7-13.6) and 9.7 (90 % CI: 9.6-9.8) days respectively. Total annual CDI-attributable cost in the US is estimated US$6.3 (Range: $1.9-$7.0) billion. Total annual CDI hospital management required nearly 2.4 million days of inpatient stay. CONCLUSIONS: This review indicates that CDI places a significant financial burden on the US healthcare system. This review adds strong evidence to aid policy-making on adequate resource allocation to CDI prevention and treatment in the US. Future studies should focus on recurrent CDI, CDI in long-term care facilities and persons with comorbidities and indirect cost from a societal perspective. Health-economic studies for CDI preventive intervention are needed.