Significant Reduction In Incidence Research Articles

Effects of patient characteristics and comorbidities on temporal trends of low-flow, low-gradient aortic stenosis phenotypes

Abstract Background Aortic stenosis (AS) is a common primary heart valve disease in the elderly. Low-flow, low-gradient (LFLG) AS is an increasingly important phenotype. Purpose To evaluate the temporal changes in incidence of severe AS phenotypes: paradoxical LFLG, classical LFLG and non-LFLG and explore risk factors that contribute to temporal trends. Methods We analyzed 25,507 consecutive transthoracic echocardiograms over 6½ years between 2013 and 2019 divided into deciles. LFLG-AS was defined as mean transvalvular pressure gradient <40 mmHg and stroke volume index (SVi) <35 mL/m2, aortic valve area (AVA) <1 cm2 or indexed AVA <0.6 cm2/m2, with either normal (paradoxical LFLG) or decreased (<40%; classical LFLG) left ventricular ejection fraction. Trends and associations with patients characteristics and comorbidities were assessed over time in deciles. Results Of 891 cases that fulfilled severe AS criteria, there were 536 cases of LFLG-AS (85 classical and 451 paradoxical LFLG-AS). There was a statistically significant increase in incidence of paradoxical LFLG-AS between each time interval (p<0.0001), while significant reduction in incidence of non-LFLG-AS (p=0.009) that was not seen with classical LFLG-AS (p=0.7) (Figure). More comprehensive echocardiographic assessment of relevant parameters over time assisted with identification of LFLG-AS cases. Intrinsic patient factors such as age and E/e' contributed towards the increasing trend of paradoxical LFLG-AS. There was a rising population aged over 70 years (p=0.01). Multivariate logistic regression analysis showed that age, sex, E/e', obesity, atrial fibrillation and heart rate were potential risk factors responsible for temporal trend towards rising paradoxical LFLG-AS incidence. There was also a gradual increase in number of patients with low transvalvular flow rate (<200mL/s) over time (p=0.04). Conclusion The incidence of paradoxical LFLG-AS is rising in a hospital echocardiogram service. The parallel increase in LV filling pressure and age in AS patients suggests the increment in LFLG-AS is related to changes to the LV myocardium. Subtypes of aortic stenosis over time Funding Acknowledgement Type of funding source: None

Disparities in the Burden of Stroke in Mexico: A National and Subnational Analysis of the Global Burden of Disease 1990–2017

Background: Stroke burden has been decreasing in high-income countries while increasing in low- to middle-income nations where ischaemic and haemorrhagic stroke are major causes of death and disability. The lack of updated epidemiological information on stroke in Mexico has motivated the development of new estimations based on available data sources and published research. Methods: Data of incidence, prevalence, deaths, premature mortality, disability, and DALYs due to cerebrovascular disease included in the Global Burden of Disease (GBD) 2017 study were analysed to identify differences on the burden of stroke types (i.e., ischaemic stroke [IS], intracerebral haemorrhage [ICH] and subarachnoid haemorrhage [SAH]), sex, age groups, and federal states from 1990 to 2017. To explore disparities due to social and health system variables, the federal states were classified using GBD’s Sociodemographic Index (SDI) and Health Access and Quality (HAQ) Index. Sources available from Mexico included vital registration data and information on stroke incidence, prevalence, and mortality from scientific literature, inpatient hospital data, population surveys, and mortality registries for the period 1990–2017. Findings: In the last 27 years, the number of stroke deaths in Mexico increased from 21,456 in 1990 to 36,653 in 2017, while the age-standardised mortality rate declined 35.8% during the period. Significant reductions in incidence, prevalence, disability, and mortality rates occurred from 1990 to 2005, with no significant changes in the declining trends from 2006 to 2017. Age-standardised mortality rates for IS and ICH were significantly reduced by 46.6% and 30%, respectively, mainly in the period 1990-2005, but not afterwards, while mortality from SAH showed non-significant changes during the whole period. DALYs and premature mortality (YLLs) age-standardised rates exhibited important decreases during the period (41.4% and 48.6%), respectively, also mainly during 1990-2005. The magnitude of decline in all metrics for ICH was more pronounced in women than men. In the case of SAH, females had higher differences in age-standardised mortality, DALYs, YLLs, YLDs, and prevalence rates at the beginning of the study (1990), but men presented higher increases during the whole period. Haemorrhagic stroke presented significantly higher age-standardised mortality, DALYs, YLLs, and incidence rates for ICH than SAH, as well as more important reductions accounted during the period. Stroke burden metrics varied widely by federal state, with less developed states (according to SDI) exhibiting the lowest improvements during the period. Interpretation: Stroke mortality in Mexico showed a decreasing trend without meaningful changes for incidence and prevalence. Reductions in DALYs were mostly explained by decrements in premature mortality and not by changes in disability burden, probably due to a precariously organised acute stroke care. During the last decade a modest declining trend on stroke burden was observed in comparison with the major reduction that occurred in the period 1900-2005. The less developed states showed the lowest reduction in stroke burden. These findings reveal the health disparities in the burden of stroke within the fragmented Mexican Healthcare System. Funding: Funding was provided by The Bill & Melinda Gates Foundation. Declaration of Interests: Vanessa De la Cruz-Gongora, D.Sc: none. Erwin Chiquete, MD, PhD: none. Hector Gomez–Dantes M.D., M.Sc: none. Lucero Cahuana-Hurtado Ph.D: none. Alejandra Montoya-Rodriguez, M.Sc: none. Carlos Cantu-Brito, M.D, Ph.D: none.

Reducing admission hypothermia in newborns at a tertiary care NICU of northern India: A quality improvement study.

Hypothermia at admission to neonatal intensive care units (NICU) is associated with increased morbidity and mortality in newborns. A baseline study at a tertiary care hospital with all out-born babies showed admission hypothermia of 82%. To reduce admission hypothermia (moderate) in newborns at least by 50% in next 6 months. A quality improvement (QI) study was planned using WHO Point of Care Quality Improvement Model (POCQI), [17] using PDSA (Plan-Do-Study-Act) cycle approach from April 2018 to March 2019, and including 427 term and preterm babies. We educated the staff, reinforced the use of caps, cling wraps, warm linen, introduced Ziploc bags and ensured adequate use of transport incubator. After 6 months, overall admission hypothermia decreased from 82% to 45%, moderate hypothermia reduced from 46% to <10% (P < 0.001) and severe hypothermia (3%) was completely eliminated. There was also significant reduction in incidence of Intraventricular hemorrhage (13% Vs 4.7%), Late onset neonatal sepsis (38% Vs 19%) and metabolic acidosis (43% Vs 28%). We were able to sustain this improvement for the next 6 months and is ongoing. The strongest predictor of hypothermia was newborns being in the phase before QI initiative was started (OR 2.36, 95% CI 1.47, 3.23). This study is a cost effective approach in reducing admission hypothermia in NICU in a resource limited setting with all outborn babies, and further decreasing the morbidity associated with it. Hence, emphasizing the importance of maintaining euthermia, not only in delivery rooms, but also during transportation.

Abstract 1103: Aspirin reduces the incidence of metastasis in a preclinical study of Braf mutant colorectal cancer

Abstract Background. Aspirin is a well-studied chemopreventive agent for the prevention of conventional colorectal adenomas and cancer. Post hoc analyses of cardiovascular prevention trials demonstrate a long-term reduction in colorectal cancer incidence and mortality with aspirin treatment. Randomized controlled trials have shown a long-term benefit for reducing colorectal cancer incidence in patients with Lynch Syndrome, a form of hereditary colorectal cancer. These findings have led to the recommendation of aspirin as a chemopreventive for colorectal cancer by the U.S. Preventive Services Task Force and Cancer Council Australia. However, future research questions have noted a lack of knowledge of the differential benefits of aspirin in preventing sessile serrated lesions versus conventional adenomas and cancer. In our study, we hypothesized that aspirin will be an effective long-term treatment for the prevention of colorectal cancer resulting from sessile serrated lesions. We aimed to investigate this in a preclinical study utilizing a murine model of Braf mutant serrated neoplasia with a primary end-point investigating cancer incidence. Methods. BrafV637E/+/Villin-CreERT2/+ mice were injected with tamoxifen (i.p. 75mg/kg) at 2 weeks of age to activate the Braf mutation within the intestine, then commenced on an aspirin-supplemented (n=78) or control standard (n=83) diet at wean. Aspirin was supplemented into the diet and provided ad libitum, at a human equivalent dose of 80-120mg per day, until sacrifice at 14 months. The gastrointestinal tract was excised and evaluated for the presence of carcinoma. In addition, the peritoneal and thoracic cavities were inspected for metastatic disease. A gastrointestinal pathologist (CL) assessed all histology sections. Results. At sacrifice, 14 months post induction of mutant Braf, all mice developed murine serrated lesions reminiscent of human sessile serrated lesions. We observed a carcinoma incidence of 31% (26/83) of which 35% (9/26) had metastasized to the liver or peritoneal cavity. When mice were treated with an aspirin-supplemented diet there was no significant reduction in carcinoma incidence (22/78, 28%, P = 0.7315). However, there was a significant reduction in the incidence of metastasis (1/22, 5%, P = 0.0134). Mice in the control group had lesions of a significantly greater size when compared to aspirin treated mice (P=0.0032). Conclusions. Aspirin resulted in a 7-fold decrease in metastases. This study demonstrates that the benefit of aspirin in preventing Braf mutant serrated neoplasia occurs at the carcinoma-metastasis phase of colorectal carcinogenesis. This could have potential clinical benefit in reducing recurrence and mortality. Citation Format: Alexandra Kane, Cheng Liu, Lochlan Fennell, Diane McKeone, Jennifer Borowsky, Barbara Leggett, Vicki Whitehall. Aspirin reduces the incidence of metastasis in a preclinical study of Braf mutant colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1103.

Comparative analysis of propeller flaps vs. modified perforator-based flaps in foot and ankle reconstruction

Lower leg, ankle, and foot defects pose a challenge for the surgeon due to the thin soft tissue cover and presence of important structures like bone, tendons, ligaments, and neurovascular bundles superficially. Since this region is prone to trauma and infection, the need arises to select an ideal flap to give a stable soft tissue cover. Propeller and perforator-based flaps are the most commonly used local flaps which can offer a durable soft tissue cover. However, they have disadvantages. Propeller flaps are more prone to venous congestion which can lead to partial or complete flap failure. Perforator-based flaps do not enjoy the freedom of rotation like propeller flaps. In this study we present a simple modification in perforator-based flaps by retaining a thin continuity of subcutaneous tissue to the minor blade of the perforator flap, which can be rotated up to 180° like propeller flaps, thus avoiding the complications of venous congestion. All patients in whom perforator-based flaps were used in the reconstruction of the lower leg, foot, and ankle region from November 2015 to January 2019 were incuded in this study. Degree of rotation, venous congestion grade, and success rate between modified-perforator flaps (MPF) and propeller flaps were compared. A total of 47 patients were included in the study. In 27 cases, traditional propeller flap technique was used. Eight cases presented with complications. In the 20 cases where a MPF was performed, one partial flap loss was observed. The mean degree of rotation was significantly higher in the MPF group (155°) if compared with the propeller flap group (137.6°) (p = 0.003).There was a statistically significant reduction in incidence of venous congestion in the MPF group (p = 0.019). The MFP herein presented seems a simpler solution to reconstruct foot and lower leg defects as it has a lesser complication rate in comparison with traditional propeller flaps. Level of evidence: Level III, therapeutic study.

Anti-vascular endothelial growth factor in neovascular age-related macular degeneration \u2013 a systematic review of the impact of anti-VEGF on patient outcomes and healthcare systems

BackgroundSystematically review the evidence describing the impact of anti–vascular endothelial growth factor (anti-VEGF) therapy on neovascular age-related macular degeneration (nAMD) patient outcomes and healthcare resource utilization.MethodsA systematic literature review was completed using Medline and EMBASE for publications prior to July 2018, and proceedings from major ophthalmology conferences (January 2016 to July 2018). The search strategy combined terms for nAMD with terms for anti-VEGF and study design. The review focused on publications describing the impact of anti-VEGF on blindness, visual impairment, vision-related quality of life (VRQoL), mortality, and costs. The search targeted data collected in epidemiological or observational studies to reflect real-world outcomes but also considered modeling-based approaches.ResultsThe use of anti-VEGF in clinical practice was associated with significant reduction in the incidence of blindness by nAMD. Population-based analyses reported reduction in incidence among the general population of 47% (9.1 cases/100,000 in 2006 to 4.8 cases/100,000 in 2011). Among patients aged ≥50 years, a reduction of 50% was observed (52.2 cases/100,000 in 2000 to 25.7 cases/100,000 in 2010). In some cases, the odds of decreased vision (defined as decline from normal to moderate, moderate to severe, or severe to blindness) fell by 41% following introduction of anti-VEGF. Patients’ VRQoL improved with treatment, with patients reporting a positive impact shortly after treatment was initiated. Change on National Eye Institute 25-Item Visual Function Questionnaire score from baseline to month 12 ranged from 0.7 to 4.4. Although nAMD patients report signs of depression and anxiety, the evidence suggests that there is no association between the use of anti-VEGF and the prevalence or diagnosis of depression. The introduction of anti-VEGF led to increased overall treatment costs due to replacement of existing less frequently administered treatments (e.g. photodynamic therapy) and increased number of patients treated (prior to anti-VEGF, only ~ 20% of patients were eligible for treatment).ConclusionsThe introduction of anti-VEGF agents has been associated with a positive impact on patient-relevant outcomes, including a significant reduction in incidence of blindness and visual impairment by nAMD. Anti-VEGF agents replaced less-effective treatments, improving patient outcomes and broadening the patient population eligible for treatment.

Japan's Ongoing Crisis on HPV Vaccination.

The Japanese government suspended proactive recommendations for the HPV vaccine in June 2013. The suspension is now in its seventh year, despite all the data pointing to the safety of the HPV vaccine. We reported a high vaccine effectiveness in the group of women vaccinated before their first intercourse (93.9%). The prevalence of cross-protected types of HPV 31/45/52 was also lower in the vaccinated group, and the vaccine effectiveness was 67.7%. Furthermore, prevalence of HPV16, 31 and 52 infection rates in the vaccinated group were obviously lower than that in the unvaccinated group, and no one had HPV18 or 45 infection in the vaccinated group. The addition of a cross-protective effect toward HPV types 31/45/52 to HPV types 16/18, which is the direct target of the bivalent HPV vaccine, may possibly prevent around 82% of invasive cervical cancer cases in Japan. With regard to the preventive effect of histological abnormalities, we also reported significant reduction in incidence of cervical intraepithelial neoplasia (CIN)3 or worse. Thus, the efficacy of the vaccine has been demonstrated for precancerous disease, and the diverse symptoms after HPV vaccination are likely functional somatic. For the future of Japanese girls, there is a need to resume the proactive recommendation of HPV vaccination and for immediate action to be taken by the Japanese government.

Central‐line‐associated bloodstream infections in a surgical paediatric intensive care unit: Risk factors and prevention with chlorhexidine bathing

The aims of the study are to evaluate the impact of a 4% chlorhexidine (CHG4%) bathing on the occurrence of central-line-associated bloodstream infection (CLABSI) and to identify risk factors (RFs) for CLABSI in our population. This is a retrospective monocentric cohort study in the paediatric surgical intensive care unit at the Necker Enfants Malades Hospital, Paris, France. All hospitalised patients with central venous catheters (CVCs) in 2015 were included. CHG4% bathing was prescribed in CLABSI high-risk patients, defined by the presence of exposition factors (EFs): constitutive or acquired immunosuppression, presence of an invasive medical device (IMD) and the carriage of Staphylococcus aureus. The overall 2015 CLABSI incidence rate was compared with 2014 CLABSI incidence rate (before CHG4% bathing). In all, 775 patients were analysed. Some 182 had at least one EF, and 49 received CHG4%. The incidence rates of CLABSI in 2014 and 2015 were, respectively, 6.1 and 2.3/1000 days CVC (P < 0.01). The presence of at least one EF was associated with the CLABSI's occurrence: odds ratio = 15.13 (95% confidence interval: 4.26-53.71; P < 0.0001), particularly acquired immunosuppression, IMD and S. aureus colonisation. Other RFs were age <1 year and carrying duration >16 days. This study showed a significant reduction in incidence of CLABSI after introduction of a targeted CHG4% bathing protocol. Presence of IMD, S. aureus colonisation, immunosuppression, age <1 year and carrying duration >16 days were CLABSI RFs. Regarding the literature, the presence of IMD seems to be underestimated in CLABSI prevention.

1230 Helicobacter pylori Eradication and Its Association With Metachronous Gastric Cancer Recurrence and Pre-Neoplastic Lesions: A Systematic Review and Meta-Analysis

INTRODUCTION: Gastric cancer is the 4th leading cause of cancer deaths worldwide displaying global variation in incidence. Helicobacter pylori (H Pylori) is known risk factor for gastric cancer. The magnitude of benefit of H pylori eradication in preventing GC recurrence is unclear. We performed a systematic review (SR) and meta-analysis (MA) of available randomized clinical trials (RCTs) to investigate the impact of H Pylori eradication on GC recurrence and precancerous lesions. METHODS: A planned literature search of Medline, PubMed and Google Scholar databases was carried out from inception to 10 February 2019. Ten (RCTs) included for analysis had H Pylori eradication as intervention arm compared to placebo. Statistical analysis was performed using statistical software RevMan, version 5.3. Random effects model and Mantel-Haenszel method for the statistical analysis was used for dichotomous data to calculate the odds ratio (OR). Two sided P values of less than 0.05 was considered statistically significant. RESULTS: 10 RCTs with total of 7,098 patients were included for final comparison. There were 3548 subjects in H Pylori group and 3550 in the placebo arm. The primary outcome was development of metachronous GC after endoscopic mucosal resection (EMR) in patients with early stage GC. H pylori group showed significant reduction in incidence of metachronous GC compared to placebo OR = 0.47, 95% confidence interval (CI) = 0.33– 0.67, P &lt; 0.0001, I2 = 0%]. Incidence of GC in high risk patients without GC at baseline showed no difference between two groups OR = 0.67, 95% CI = 0.42–1.07, P = 0.09, I2 = 0%). H Pylori eradication group showed statistically significant improvement in AG and IM from baseline compared to placebo group with OR = 2.10, 95% CI = 1.19–3.71, P = 0.01, I2 = 87% and OR = 2.08, 95% CI = 1.28–3.36, P = 0.003, I2 = 30% respectively. RCTs with mean duration of follow up &gt;5 years for GC incidence showed statistically significant reduction in GC incidence in H Pylori eradication group OR = 0.55, 95% CI = 0.40-0.76, P = 0.0003, I2 = 0%. CONCLUSION: Our meta-analysis showed the beneficial role of H Pylori eradication in decreasing GC recurrence for patients with early GC post EMR. H Pylori group also showed improvement in AG and IM grades compared to placebo. There was no difference in GC incidence in asymptomatic patients without GC at baseline between the two groups. More studies are needed from the North America, Europe and other non-Asian countries to better understand the differences in geographical regions.

897 Aggressive Hydration With Lactated Ringer for Prevention of Post-ERCP Pancreatitis: A Systematic Review and Meta-Analysis

INTRODUCTION: Pancreatitis is the leading complication of endoscopic retrograde cholangiopancreatography (ERCP), resulting in considerable morbidity and, rarely, in death. Hydration is a mainstay of treatment for acute pancreatitis, independent of etiology. Aggressive hydration with lactated ringers (LR) has been suggested for prevention of post-ERCP pancreatitis (PEP). However, recent studies have reported contradictory results. The aim of this study was to perform a systematic review and meta-analysis to evaluate the impact of aggressive LR hydration in PEP incidence. METHODS: A comprehensive search of MEDLINE, EMBASE, Scopus, Cochrane Database was conducted from each database’s inception to search for comparative studies of aggressive LR vs standard therapy for prevention of PEP. Aggressive LR is defined as 3 ml/kg/hr during the procedure, a 20 ml/kg bolus after the procedure, and 3 ml/kg/hr for 8 hours following the procedure. The primary outcome of interest was PEP rates. Secondary outcomes were other adverse events. Outcomes were reported as pooled odds ratio (OR) with 95% confidence intervals (CI) with statistical significance (P &lt; 0.05). RevMan 5.3 software was used for statistical analysis. RESULTS: Eight studies (7 randomized controlled trials and one prospective study) with a total of 3248 patients were included in the meta-analysis. There were 1623 patients in the aggressive LR group and 1625 patients in the standard therapy group. There was no difference between the groups regarding age and sex. Patients in the aggressive arm received 3 ml/kg/hr during the procedure, a 20 ml/kg bolus after the procedure, and 3 ml/kg/hr for 8 hours following the procedure compared to 1.5 ml/kg/hour during the procedure and for 8 hours after the procedure without a bolus in the standard hydration arm. The mean total fluid administered in the two groups was reported in 2 studies with a pooled mean of 3.25 L in the aggressive and 1.47 L in the standard group (P &lt; 0.001). The PEP rate was significantly lower in the aggressive LR arm compared to standard therapy (OR 0.33, 95% CI 0.21-0.50, P &lt; 0.0001). There was no heterogeneity between the studies (I2 = 0%). Peripheral edema as an adverse outcome of aggressive LR therapy was reported only in 2 (0.69%) patients in 2 studies and was managed conservatively. No significant adverse events were reported in any study. CONCLUSION: Aggressive hydration with LR is associated with a significant reduction in incidence of PEP, and therefore, should be practiced routinely.

P2.01-24 CANOPY-2: Phase 3 Study of Canakinumab Plus Docetaxel as Second/Third Line Therapy in Locally Advanced/Metastatic NSCLC

Pembrolizumab, a PD-1 inhibitor combined with platinum-based chemotherapy is standard first-line therapy for eligible patients without a targetable mutation, stage IIIB/IV NSCLC. Currently, there is no data to guide treatment following progression on sequential/concomitant use of platinum-based chemotherapy and PD-1 inhibitors. Activation of inflammation and elevated baseline C-reactive protein (CRP) levels are associated with lower response/resistance to immunotherapies. Canakinumab is a high-affinity anti-IL-1β monoclonal antibody that demonstrated a significant reduction in incidence of fatal and nonfatal lung cancer in patients with increased CRP levels (CANTOS study). CANOPY-2 (NCT03626545) is a multicenter, phase 3 study evaluating safety and efficacy of docetaxel ± canakinumab in patients with squamous/non-squamous, stage IIIB-IV NSCLC. This study includes a safety run-in part (part 1 – open label) to confirm recommended phase 3 regimen (RP3R) to be used in randomized phase 3 part (part 2 – double blind, placebo-controlled). Key inclusion criteria: adult patients pretreated with one prior platinum-based chemotherapy and one prior PD-(L)1 inhibitor therapy for locally advanced/metastatic disease, either together/sequentially and then progressed; ECOG PS 0-1. In part 1, ∼9 patients will be enrolled to have at least 6 evaluable patients and ∼226 patients will be randomized (1:1, stratified by number of prior lines of therapy and histology) in part 2 to docetaxel ± canakinumab. Primary objectives: to confirm RP3R of canakinumab + docetaxel, as determined by incidence of DLTs in first 42 days of administration (part 1) and overall survival (part 2). Secondary objectives are to assess efficacy (overall response rate, disease control rate, duration of response, time to response, progression-free survival by investigator per RECIST v1.1), safety, pharmacokinetics, immunogenicity of canakinumab, and patient reported outcomes. Enrollment is ongoing. Section not applicable Section not applicable

Comparison of meperidine, tramadol and fentanyl for post-spinal shivering prevention during cesarean delivery: A double-blind randomized controlled trial.

To assess the effects of intravenously administered meperidine, fentanyl and tramadol in reducing the incidence, onset time and severity of the shivering response in parturients during cesarean delivery under spinal anesthesia. Secondary outcomes included patient satisfaction and sedation scores. After Ethics board approval and informed written consent, 350 parturients (ASA physical status I or II), between 20 and 40 years of age, undergoing emergency or elective cesarean delivery under spinal anesthesia were recruited. Parturients were then randomly allocated to seven study groups: normal saline (control), low-dose meperidine (0.5 mg/kg), high-dose meperidine (0.75 mg/kg), low-dose fentanyl (0.5 mcg/kg), high-dose fentanyl (0.75 mcg/kg), low-dose tramadol (0.5 mg/kg) and high-dose tramadol (0.75 mg/kg). The incidence, onset time and severity of shivering, along with patient satisfaction and sedation scores were measured. All study drugs showed significant reduction in incidence, onset time and severity of shivering and greater satisfaction scores compared to the control group (P < 0.01). Within each drug class, no significant differences in shivering were found between the high-dose and low-dose groups. Among study drugs, low-dose tramadol was superior due to shivering prevention and significantly reduced sedation. Intravenously administered meperidine, fentanyl and tramadol reduce shivering incidence, onset time and severity in parturients undergoing cesarean delivery following spinal anesthesia. Importantly, low-dose intravenous tramadol (0.5 mg/kg) allowed shivering prevention and low sedation scores, thereby offering greater parturient satisfaction and better maternal-newborn bonding.

Long-Term Vitamin K Antagonists and Cancer Risk: A Systematic Review and Meta-Analysis.

Vitamin K antagonists (VKAs) remain one of the most commonly used anticoagulation therapies. The potential anticancer effect of long-term use of VKAs has been a matter of debate with conflicting results. Our goal was to perform a systematic review and meta-analysis examining the association between long-term VKAs use and cancer risk. Systematic searches of multiple major databases were performed from inception until January 2018. We included studies of adults that compared incidence of any cancer between ≥6 months use of VKAs (long-term group) and <6 months use of VKAs or nonuse (control group). Primary outcome was all-cancer incidence and secondary outcomes were cancer-specific incidence, all-cause death and cancer-specific mortality. Hazard ratios (HRs) were pooled using a random-effects model, and individual studies were weighted using inverse variance. We identified 9 observational studies that included 1,521,408 patients. No randomized trials were identified. In comparison to control, long-term use of VKAs was associated with a significant reduction in incidence of all cancers (HR, 0.84; 95% confidence interval [CI], 0.81-0.88; P<0.001). In a prespecified subgroup analysis, long-term use of VKAs demonstrated a significant reduction in all-cancer incidence when compared with control in individuals whose indication for VKAs were venous thromboembolism (HR, 0.69; 95% CI, 0.52-0.90; P=0.007). The use of long-term VKAs, for any indication, is associated with lower cancer incidence. This finding could have important clinical implications for the choice of oral anticoagulation therapies among specific patients with a higher baseline risk of cancer.

Efficacy of ketamine soaked laryngeal pack in postoperative sore throat after nasal surgeries

Background: Post-operative sore throat (POST) occurs in 21-65% of patients which commonly arises after tracheal intubation and throat packing in patients undergoing general anaesthesia. The aim of the study was to see if ketamine soaked laryngeal pack attenuates POST in postoperative period. Methods: The present study was conducted as a prospective, randomized, double-blind clinical study. After written informed consent, 80 patients belonging to American Society of Anaesthesiologists physical status I-II in the age group 20-50 years, of either sex undergoing nasal surgery under general anaesthesia were enrolled. Patients were randomized into two groups; control group (C) in which laryngeal packing gauge soaked in 5 ml normal saline and group ketamine (K) in which the laryngeal packing gauge soaked in1 ml of ketamine 50 mg (50mg/ ml) with 4.0 ml of normal saline. Incidence and severity of POST was assessed at 0(on reaching post-anaesthesia care unit), 2, 4, 8, 12 and 24 hours post-operatively and graded on a four-point scale (0-3). Results: In present study there was a significant reduction in incidence and attenuation of POST at 0 (on arrival at the post-anaesthetic care unit), 2, 4, 8 hours in postoperative period in ketamine group in comparison to normal saline group. Conclusion: Laryngeal pack soaked in 50 mg ketamine is a simple and effective means in reducing the incidence and severity of postoperative sore throat in patients receiving general anesthesia with endotracheal intubation in nasal surgeries.

Association Between Baseline, Achieved, and Reduction of CRP and Cardiovascular Outcomes After LDL Cholesterol Lowering with Statins or Ezetimibe: A Systematic Review and Meta-Analysis.

BackgroundSeveral lipid‐lowering therapies reduce CRP (C‐reactive protein) independently of LDL‐C (low‐density lipoprotein cholesterol) reduction, but the association between CRP parameters and benefits from more‐intensive LDL‐C lowering is inconclusive. We aimed to determine whether the benefits of more‐ versus less‐intensive LDL‐C lowering on cardiovascular events related to baseline, achieved, or magnitude of reduction in CRP concentrations.Methods and ResultsPubMed, EMBASE, and Cochrane were searched through July 2, 2018. We included randomized controlled cardiovascular outcome trials of LDL‐C lowering with statins or ezetimibe. Two reviewers independently extracted study data and rated study quality. Data were analyzed using meta‐analysis and metaregression analysis. Rate ratios of mortality and cardiovascular outcomes associated with baseline, achieved, and magnitude reduction of CRP concentration were calculated. Twenty‐four trials were included, with 171 250 patients randomly assigned to more‐ or less‐intensive LDL‐C–lowering treatments. Median follow‐up duration was 4.2 years. More‐intensive LDL‐C lowering resulted in a significant reduction in incidences of all outcomes. Compared with less‐intensive LDL‐C lowering, more‐intensive LDL‐C lowering was associated with less reductions in myocardial infarction with a higher baseline CRP concentration (change in rate ratios per 1‐mg/L increase in log‐transformed CRP, 1.12 [95% CI, 1.04–1.22; P=0.007]), but not other outcomes. Similar risk reductions occurred for more‐ versus less‐intensive LDL‐C–lowering therapy regardless of the magnitude of CRP reduction or the achieved CRP level for all outcomes.ConclusionsBaseline CRP concentrations might be associated with the benefits of LDL‐C lowering on myocardial infarction, but no other outcomes, whereas the achieved and magnitude of reduction in CRP did not seem to have an important association.

The Effect of Perinatal Fish Oil Supplement on Perinatal Depression: A Systemic Review and Meta- Analysis of Randomized Clinical Trials

Background: Perinatal depression is a common complication of pregnancy and can have severe and long-termadverse effects on both mother and infant. Randomized controlled trials (RCT) assessing the effect of fish oilsupplements on perinatal depression have shown mixed results.Objectives: We performed a systematic review and meta-analysis to assess the effects of fish oil supplementation during pregnancy on perinatal depression.Methods: A comprehensive search of MEDLINE (PubMed), EMBASE, and Cochrane Central Registry were conducted in adherence with the PRISMA guideline. Only RCTs published in English from January 2000 to date were included. The participants were pregnant women receiving fish oil supplementation or placebo. Summary effect measure of each study was converted to a common effect measure (log odds ratio) and its variance was calculated to estimate the pooled odds ratio and its 95% confidence Interval using random Effects model. Heterogeneity was assessed used restricted maximum likelihood method.Results: Nine trials were included in our analysis (2,979 women). Prevention Cohort (n = 5): Fish oil supplementation during pregnancy was associated with reduced risk of developing perinatal depression (OR: 0.87; CI: 0.076 to 0.99; p = 0.03). Treatment Cohort (n = 4) Fish oil supplementation during pregnancy was associated with reduced risk of persistent perinatal depression during postpartum period but did not reach statistical significance.Conclusion: In conclusion, a meta-analysis of included RCTs data shows a significant reduction in incidences of perinatal depression in women who received fish oil supplements during pregnancy. However, there was no evidence for a similar effect among women diagnosed with perinatal depression or women with major depressive disorder.

Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation

Herpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster. To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients. Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT. Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n = 922) or placebo (n = 924) administered into the deltoid muscle; the first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter. The primary end point was occurrence of confirmed herpes zoster cases. Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [37%] women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study. During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P < .001), equivalent to 68.2% vaccine efficacy. Of 8 secondary end points, 3 showed significant reductions in incidence of postherpetic neuralgia (vaccine, n=1; placebo, n=9; IRR, 0.1; 95% CI, 0.00-0.78; P = .02) and of other prespecified herpes zoster-related complications (vaccine, n=3; placebo, n=13; IRR, 0.22; 95% CI, 0.04-0.81; P = .02) and in duration of severe worst herpes zoster-associated pain (vaccine, 892.0 days; placebo, 6275.0 days; hazard ratio, 0.62; 95% CI, 0.42-0.89; P = .01). Five secondary objectives were descriptive. Injection site reactions were recorded in 86% of vaccine and 10% of placebo recipients, of which pain was the most common, occurring in 84% of vaccine recipients (grade 3: 11%). Unsolicited and serious adverse events, potentially immune-mediated diseases, and underlying disease relapses were similar between groups at all time points. Among adults who had undergone autologous HSCT, a 2-dose course of recombinant zoster vaccine compared with placebo significantly reduced the incidence of herpes zoster over a median follow-up of 21 months. ClinicalTrials.gov Identifier: NCT01610414.

Evaluation of future cervical cancer risk in Japan, based on birth year

In 2013, following the Ministry of Health, Labor and Welfare (MHLW)'s announced suspension of its vaccine recommendation due to media reports of adverse events, HPV vaccination dropped to almost 0%. Here, we analyzed, by birth year, the cumulative vaccinations for girls up to age 16 (maximum age for public subsidies) and the results of cervical cancer screening in Matsuyama City. The incidence of CIN3 or worse was 0.09% (7/7872) for these unvaccinated generation born between 1991 and 1993, and 0.00% (0/7389) for the vaccination generation born between 1994 and 1996. This study is the first to show the significant reduction in incidence of CIN3+depending on birth year in Japan. We must keep in mind that the unacceptable high risk for cervical cancer has already begun for an entire new generation of unvaccinated girls born in or after 2000. This data encourages a resumption of MHLW's recommendation for HPV vaccination.

Evaluation of future cervical cancer risk in Japan, based on birth year

In 2013, following the Ministry of Health, Labor and Welfare (MHLW)’s announced suspension of its vaccine recommendation due to media reports of “adverse events”, HPV vaccination dropped to almost 0%. Here, we analyzed, by birth year, the cumulative vaccinations for girls up to age 16 (maximum age for public subsidies) and the results of cervical cancer screening in Matsuyama City. The incidence of CIN3 or worse was 0.09% (7/7872) for these unvaccinated generation born between 1991 and 1993, and 0.00% (0/7389) for the vaccination generation born between 1994 and 1996. This study is the first to show the significant reduction in incidence of CIN3+depending on birth year in Japan. We must keep in mind that the unacceptable high risk for cervical cancer has already begun for an entire new generation of unvaccinated girls born in or after 2000. This data encourages a resumption of MHLW’s recommendation for HPV vaccination.

Sudden infant death syndrome: current perspectives.

Despite significant reductions in incidence since the introduction of safe infant sleeping recommendations, sudden infant death syndrome is still the major cause of neonatal death in western countries. In the United States, over 2500 infants die suddenly and unexpectedly each year with nearly 100 deaths annually in Australia. Health professionals play a critical role in advising parents how to sleep their infants safely to minimise the risk of sudden infant death syndrome and sleeping accidents. Infants should be placed supine to sleep in a cot with a firm well-fitting mattress in the parental bedroom with no soft or loose bedding which could obstruct the airway. Exposure to smoking both before and after birth should be minimised. Breastfeeding should be encouraged, as should immunisation. Dummies can be recommended after breastfeeding has been established. This review outlines the evidence behind these recommendations.