Gender Differences in Patients with Atrial Fibrillation Receiving Oral Anticoagulants.

Background: Gender is a well-recognized risk factor in atrial fibrillation (AF)-related ischemic stroke. The association of gender with the use of oral anticoagulants (OACs) and prognosis remains unknown. Methods: The National Health Insurance Research Database in Taiwan identified 203,775 patients with AF aged ≥ 20 years from 2012 to 2018, with 55.4% of males. Our main study cohort included 67,426 patients using OACs. The study endpoints include death, ischemic stroke, intracranial hemorrhage, major bleeding, and composite adverse events. Results: Significant differences were found in baseline characteristics between sexes. Female patients with AF were older and had higher CHA 2 DS 2 -VASc and HAS-BLED scores. Non-vitamin K antagonist oral anticoagulant (NOAC) use was more prominent in females while the use of warfarin was similar in both sexes. The distribution of baseline characteristics between the warfarin and NOAC groups in both sexes was much alike. Among the whole study cohort, NOAC was associated with a decreased risk of clinical endpoints compared to warfarin, which remained the same in subgroup analyses of both sexes. Additionally, a greater risk reduction of ischemic stroke with NOAC was observed in female patients compared to male patients (adjusted hazard ratio: 0.517 in males, 0.425 in females, interaction p = 0.040). Conclusions: This nationwide cohort demonstrated the differences between male and female patients with AF, including baseline characteristics, risk profiles, and medication use. Despite great differences in baseline demographic data, NOAC was associated with better clinical outcomes compared to warfarin in both sexes, and females benefited more than males in preventing ischemic stroke using NOACs.

Non-vitamin K antagonist oral anticoagulants versus warfarin in AF patients ≥ 85 years.

BACKGROUND: Atrial fibrillation (AF) prevalence and its risk of stroke rise with ageing. We aimed to investigate the outcomes of NOAC and warfarin in AF patients aged ≥ 85 years. METHODS: This is a retrospective study using Taiwan National Health Insurance Research Database. A total of 15,361 patients aged ≥ 85 years with AF on oral anticoagulants were identified. The end points included ischaemic stroke, intracranial haemorrhage (ICH), major bleeding, all-cause mortality and composite adverse events (ICH or major bleeding or all-cause mortality). Clinical outcomes were compared between each NOAC and warfarin after propensity matching. RESULTS: Before propensity matching, patients taking warfarin were older, more female with more comorbidities than NOACs users. After propensity matching, baseline characteristics did not differ significantly between matched subjects receiving warfarin and each NOAC. Compared to warfarin, dabigatran was associated with a lower risk of ICH (hazard ratio [HR] 0.496), mortality (HR 0.558) and adverse events (HR 0.628), while rivaroxaban was associated with a lower risk of ischaemic stroke (HR 0.781), ICH (HR 0.453), mortality (HR 0.558) and adverse events (HR 0.636). Apixaban was associated with a lower risk of mortality (HR 0.488) and adverse events (HR 0.557) compared to warfarin. (all P < .05). CONCLUSION: For the efficacy, NOACs were associated with a comparable or lower risk of ischaemic stroke compared to warfarin. For adverse events, NOACs were associated with a lower risk of all-cause mortality and composite adverse events. In the elderly AF population, NOACs could be a more favourable choice for stroke prevention.

Molecular Imaging and Preclinical Studies of Radiolabeled Long-Term RGD Peptides in U-87 MG Tumor-Bearing Mice.

The Arg-Gly-Asp (RGD) peptide shows a high affinity for αvß3 integrin, which is overexpressed in new tumor blood vessels and many types of tumor cells. The radiolabeled RGD peptide has been studied for cancer imaging and radionuclide therapy. We have developed a long-term tumor-targeting peptide DOTA-EB-cRGDfK, which combines a DOTA chelator, a truncated Evans blue dye (EB), a modified linker, and cRGDfK peptide. The aim of this study was to evaluate the potential of indium-111(111In) radiolabeled DOTA-EB-cRGDfK in αvß3 integrin-expressing tumors. The human glioblastoma cell line U-87 MG was used to determine the in vitro binding affinity of the radiolabeled peptide. The in vivo distribution of radiolabeled peptides in U-87 MG xenografts was investigated by biodistribution, nanoSPECT/CT, pharmacokinetic and excretion studies. The in vitro competition assay showed that 111In-DOTA-EB-cRGDfK had a significant binding affinity to U-87 MG cancer cells (IC50 = 71.7 nM). NanoSPECT/CT imaging showed 111In-DOTA-EB-cRGDfK has higher tumor uptake than control peptides (111In-DOTA-cRGDfK and 111In-DOTA-EB), and there is still a clear signal until 72 h after injection. The biodistribution results showed significant tumor accumulation (27.1 ± 2.7% ID/g) and the tumor to non-tumor ratio was 22.85 at 24 h after injection. In addition, the pharmacokinetics results indicated that the 111In-DOTA-EB-cRGDfK peptide has a long-term half-life (T1/2λz = 77.3 h) and that the calculated absorbed dose was safe for humans. We demonstrated that radiolabeled DOTA-EB-cRGDfK may be a promising agent for glioblastoma tumor imaging and has the potential as a theranostic radiopharmaceutical.

[Nursing Experience of a Child With Difficulty Breathing With End-Stage Niemann-Pick Disease Type C].

This case report describes a nursing experience providing end-of-life care to a child with Niemann-Pick disease type C. The period of nursing care was from April to June 2018. After comprehensive nursing and family assessment, dyspnea and caregiver's role strain were identified as the primary nursing-care problems. Niemann-Pick is a rare disease caused by genomic abnormalities. Patients with this disease are unable to metabolize lipids, which accumulate in organs, causing hepatosplenomegaly, dyspnea, and central nervous system degeneration. There is a lack of relevant experience in medical and nursing care due to the small number of cases worldwide. It is difficult to predict the progress of this disease and the life expectancy of the patient. The complex indications of this disease complicate the caregiver burden and process of end-of-life care. Thus, the multi-disciplinary team integrated the discharge preparations, symptom control skills, and related resources to build consensus with the family. We provided nursing care continuously from hospital to home as well as improved quality of care and family cohesion and reduced caregiver load. We hope that sharing this experience provides a reference for discharge planning and end-of-life care for children with rare diseases.

Rate-control treatment and mortality in atrial fibrillation.

BACKGROUND: Current American and European guidelines emphasize the importance of rate-control treatments in treating atrial fibrillation with a Class I recommendation, although data on the survival benefits of rate control are lacking. The goal of the present study was to investigate whether patients receiving rate-control drugs had a better prognosis compared with those without rate-control treatment. METHODS AND RESULTS: This study used the National Health Insurance Research Database in Taiwan. There were 43 879, 18 466, and 38 898 patients with atrial fibrillation enrolled in the groups receiving ß-blockers, calcium channel blockers, and digoxin, respectively. The reference group consisted of 168 678 subjects who did not receive any rate-control drug. The clinical end point was all-cause mortality. During a follow-up of 4.9±3.7 years, mortality occurred in 88 263 patients (32.7%). After adjustment for baseline differences, the risk of mortality was lower in patients receiving ß-blockers (adjusted hazard ratio=0.76; 95% confidence interval=0.74-0.78) and calcium channel blockers (adjusted hazard ratio=0.93; 95% confidence interval=0.90-0.96) compared with those who did not receive rate-control medications. On the contrary, the digoxin group had a higher risk of mortality with an adjusted hazard ratio of 1.12 (95% confidence interval=1.10-1.14). The results were observed consistently in subgroup analyses and among the cohorts after propensity matching. CONCLUSIONS: In this nationwide atrial fibrillation cohort, the risk of mortality was lower for patients receiving rate-control treatment with ß-blockers or calcium channel blockers, and the use of ß-blockers was associated with the largest risk reduction. Digoxin use was associated with greater mortality. Prospective, randomized trials are necessary to confirm these findings.

Validation of a Modified CHA2DS2-VASc Score for Stroke Risk Stratification in Asian Patients With Atrial Fibrillation: A Nationwide Cohort Study.

BACKGROUND AND PURPOSE: The age threshold for an increased stroke risk for patients with atrial fibrillation may be different for Asians and non-Asians. We hypothesized that a modified CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65-74 years, female) scheme, mCHA2DS2-VASc, which assigned one point for patients aged 50 to 74 years, may perform better than CHA2DS2-VASc score for stroke risk stratification in Asians. METHODS: This study used the Taiwan National Health Insurance Research Database, which included 224 866 newly diagnosed atrial fibrillation patients. The predictive accuracies of ischemic stroke of CHA2DS2-VASc and mCHA2DS2-VASc scores were compared among 124 271 patients without antithrombotic therapies. From the whole cohort, 15 948 patients had a CHA2DS2-VASc score 0 (males) or 1 (females), and 8654 patients had an mCHA2DS2-VASc score 1 (males) or 2 (females). The latter were categorized into 3 groups, that is, no treatment, antiplatelet therapy, and warfarin, and the risks of ischemic stroke and intracranial hemorrhage (ICH) were compared. RESULTS: During a follow-up of 538 653 person-years, 21 008 patients experienced ischemic stroke. The mCHA2DS2-VASc performed better than CHA2DS2-VASc score in predicting ischemic stroke assessed by C indexes and net reclassification index. For 8654 patients having an mCHA2DS2-VASc score of 1 (males) or 2 (females) because of the resetting of the age threshold, use of warfarin was associated with a 30% lower risk of ischemic stroke and a similar risk of ICH compared with nontreatment. Net clinical benefit analyses also favored the use of warfarin in different weighted models. CONCLUSIONS: In this Asian atrial fibrillation cohort, the mCHA2DS2-VASc score performed better than the CHA2DS2-VASc and would further identify atrial fibrillation patients who may derive a positive net clinical benefit from oral anticoagulation.

Incidence and risk factors for new-onset atrial fibrillation among patients with end-stage renal disease undergoing renal replacement therapy.

Atrial fibrillation (AF) is prevalent in end-stage renal disease (ESRD) patients and negatively impacts patient outcomes. We explored the incidence and risk factors for new-onset AF among patients with ESRD undergoing renal replacement therapy, without a prior history of AF, retrieved from Taiwan's National Health Insurance Research Database (NHIRD). For each of 134,901 patients with ESRD, one age- and gender-matched control and one similarly matched patient with chronic kidney disease (CKD), a total of 404,703 patients, were selected from the NHIRD. The study endpoint was the occurrence of new-onset AF and patients were followed an average of 5.1 years. The incidence rates of AF were 12.1, 7.3, and 5.0 per 1000 person-years for ESRD, CKD, and control patients, respectively. Among patients with ESRD, age, hypertension, heart failure, coronary artery disease, peripheral arterial occlusive disease, and chronic obstructive pulmonary disease were significant risk factors for new-onset AF. Thus, patients with ESRD had a significantly higher risk of new-onset AF. The presence of multiple risk factors was associated with a higher possibility of AF occurrence.

Incidence and risk of atrial fibrillation in sleep-disordered breathing without coexistent systemic disease.

BACKGROUND: Although the link between sleep-disordered breathing (SDB) and atrial fibrillation (AF) has been reported, a population-based longitudinal cohort study was lacking. The goal of the present study was to investigate the AF risk carried by SDB, using the National Health Insurance Research Database in Taiwan. METHODS AND RESULTS: From 2000 to 2001, a total of 579,521 patients who had no history of cardiac arrhythmias or significant comorbidities were identified. Among them, 4,082 subjects with the diagnosis of SDB were selected as the study group, and the remaining 575,439 subjects constituted the control group. The study endpoint was the occurrence of new-onset AF. During a follow-up of 9.2±2.0 years, there were 4,023 patients (0.7%) experiencing new-onset AF. The occurrence rate of AF was higher in patients with SDB compared to those without it (1.3% vs. 0.7%, P<0.001). The AF incidences were 1.38 and 0.76 per 1,000 person-years for patients with and without SDB, respectively. After anadjustment for age and sex, SDB was a significant risk factor of AF with a hazard ratio of 1.536. The AF risk increased with increasing clinical severity of SDB, represented by the requirement of continuous positive airway pressure use. CONCLUSIONS: SDB itself, without the coexistence of other systemic diseases, was a risk factor of AF.

Atrial fibrillation and the risk of ischemic stroke: does it still matter in patients with a CHA2DS2-VASc score of 0 or 1?

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is an independent risk factor for stroke. Recent studies have demonstrated that the CHA(2)DS(2)-VASc scheme is useful for selecting patients who are truly at low risk. The goal of the present study was to compare the risk of ischemic stroke among AF patients with a CHA(2)DS(2)-VASc score of 0 (male) or 1 (female) with those without AF. METHODS: The study enrolled 509 males (CHA(2)DS(2)-VASc score=0) and 320 females (CHA(2)DS(2)-VASc score=1) with AF who did not receive any antithrombotic therapy. Patients were selected from the National Health Insurance Research Database in Taiwan. For each study patient, 10 age-matched and sex-matched subjects without AF and without any comorbidity from the CHA(2)DS(2)-VASc scheme were selected as controls. The clinical end point was the occurrence of ischemic stroke. RESULTS: During a follow-up of 57.4 ± 35.7 months, 128 patients (1.4%) experienced ischemic stroke. The event rate did not differ between groups with and without AF for male patients (1.6% vs 1.6%; P=0.920). In contrast, AF was a significant risk factor for ischemic stroke among females (hazard ratio, 7.77), with event rates of 4.4% and 0.7% for female patients with and without AF (P<0.001). CONCLUSIONS: AF males with a CHA(2)DS(2)-VASc score of 0 were at true low risk for stroke, which was similar to that of non-AF patients. However, AF females with a score of 1 were still at higher risk for ischemic events than non-AF patients.

Cool seasons are related to poor prognosis in patients with infective endocarditis.

Many cardiac diseases demonstrate seasonal variations in the incidence and mortality. This study was designed to investigate whether the mortality of infective endocarditis (IE) was higher in cool seasons and to evaluate the effects of cool climate for IE. We enrolled 100 IE patients with vegetations in our hospital. The temperatures of the IE episodes were defined as the monthly average temperatures of the admission days. The average temperatures in the cool (fall/winter) and warm seasons (spring/summer) were 19.2°C and 27.6°C, respectively. In addition, patients admitted with the diagnosis of IE were identified from the National Health Insurance Research Database (NHIRD) and the in-hospital mortality rates in cool and warm seasons were compared to validate the findings derived from the data of our hospital. The mortality rate for IE was significantly higher in fall/winter than in spring/summer which presents consistently in the patient population of our hospital (32.7% versus 12.5%, p = 0.017) and from NHIRD (10.4% versus 4.6%, p = 0.019). IE episodes which occurred during cool seasons presented with a higher rate of heart failure (44.2% versus 22.9%, p = 0.025) and D-dimer level (5.5 ± 3.8 versus 2.4 ± 1.8 µg/ml, p = 0.017) at admission than that of warm seasons. These results may reflect the impact of temperatures during the pre-hospitalized period on the disease process. In the multivariate analysis, Staphylococcal infection, left ventricular hypertrophy, left ventricular systolic dysfunction and temperature were the independent predictors of mortalities in IE patients.

The impact of antimicrobial stewardship program designed to shorten antibiotics use on the incidence of resistant bacterial infections and mortality.

Reassessing the continuing need for and choice of antibiotics by using an antibiotic "time out'' program may reduce unnecessary treatment. This study aimed to explore the effect of an antibiotic stewardship program (ASP) on the antibiotics consumption, incidence of resistant bacterial infections and overall hospital mortality in a tertiary medical center during the study period 2012-2014. An ASP composed of multidisciplinary strategies including pre-prescription approval and post-approval feedback and audit, and a major "time out'' intervention (shorten the default antibiotic prescription duration) usage was introduced in year 2013. Consumption of antibiotics was quantified by calculating defined daily doses (DDDs). Interrupted time series (ITS) analysis was used to explore the changes of antibiotics consumption before and after intervention, accounting for temporal trends that may be unrelated to intervention. Our results showed that following the intervention, DDDs showed a decreased trend in overall (in particular the major consumed penicillins and cephalosporins), in both intensive care unit (ICU) and non-ICU, and in non-restrictive versus restrictive antibiotics. Importantly, ITS analysis showed a significantly slope change since intervention (slope change p value 0.007), whereas the incidence of carbapenem-resistant and vancomycin-resistant pathogens did not change significantly. Moreover, annual overall mortality rates were 3.0%, 3.1% and 3.1% from 2012 to 2014, respectively. This study indicates that implementing a multi-disciplinary strategy to shorten the default duration of antibiotic prescription can be an effective manner to reduce antibiotic consumption while not compromising resistant infection incidence or mortality rates.

The epidemiology and etiologies of respiratory tract infection in Northern Taiwan during the early phase of coronavirus disease 2019 (COVID-19) outbreak.

BACKGROUND: Coronavirus disease 2019 (COVID-19) manifests symptoms as common etiologies of respiratory tract infections (RTIs). During the pandemic of COVID-19, identifying the etiologies correctly from patients with RTI symptoms was crucial in not only disease control but preventing healthcare system from collapsing. By applying sensitive PCR-based molecular assays, we detected the etiologic agents and delineated the epidemiologic picture of RTIs in the early phase of COVID-19 pandemic. METHODS: From December 2019 to February 2020, we screened patients presented with RTIs using multiplex PCR-based diagnostic assays. Data from pediatric and adult patients were compared with different months and units in the hospital. RESULTS: Of all 1631 patients including 1445 adult and 186 pediatric patients screened, 8 viruses and 4 bacteria were identified. Positive rates were 25% in December, 37% in January, and 20% in February, with pediatric patients having higher positive rates than adults (Ps < 0.001). In pediatric patients, RhV/EnV was the most commonly detected, followed by parainfluenza viruses. Most Mycoplasma pneumoniae infection occurred in pediatric patients. RhV/EnV was the most commonly detected agent in pediatric patients admitted to intensive care units (ICUs), while influenza accounted for the majority of adult cases with critical illness. Noticeably, seasonal coronavirus ranked second in both adult and pediatric patients with ICU admission. CONCLUSION: While we focused on the pandemic of COVID-19, common etiologies still accounted for the majority of RTIs and lead to severe diseases, including other seasonal coronaviruses.

The clinical manifestations and interval changes of reverse-transcriptase quantitative polymerase chain reactions among different specimens of coronavirus disease 2019 patients.

BACKGROUND: Since December 2019, a number of cases and deaths due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have been reported worldwide. In spite of clinical manifestations similar to the SARS-CoV epidemic in 2003, affected organs and severity are yet to be defined. Moreover, viral load alterations and viral shielding among different specimens remained scarce. Therefore, clarifying clinical presentations and correlations among viral loads, disease severity, and viral shielding of SARS-CoV-2 infection is crucial in the disease prevention. METHODS: The clinical courses of SARS-CoV-2 cases were presented through Gantt charts. Laboratory examinations and reverse-transcriptase quantitative polymerase chain reactions (RT-qPCR) among different specimens were tested periodically. Cycle thresholds (CT) were recorded and presented as viral loads. RESULTS: From March 2020 to April 2020, 4 SARS-CoV-2 cases were presented, of which, cases 1 and 2 manifested the symptoms severer than cases 3 and 4, along with higher serum lactate dehydrogenase levels and graded for lymphocytopenia. Case 4 initially exhibited anosmia but recovered within a short period. Curves of the CT of all the cases, except case 2, concaved upward after prescribing hydroxychloroquine (HCQ) and azithromycin. Except for case 4, the CT in most stool specimens remained undetectable; however, none of the cases presented gastrointestinal symptoms. Surprisingly, the CT values of the saliva specimens were inconsistent with those of the nasopharyngeal swabs and sputum. CONCLUSION: SARS-CoV-2 manifests various symptoms. Sudden onset of central nervous system symptoms should be considered. The timing of HCQ and azithromycin administration might be a key factor in the viral load reduction. Positive prediction values of RT-qPCR of different specimens should be tested carefully to prevent false-negative results.

Anal human papillomavirus and its associations with abnormal anal cytology among men who have sex with men.

Human papillomavirus (HPV) infection contributes to most anal cancers and premalignant intraepithelial lesions. This study investigated anal HPV infections and cytological abnormalities among men who have sex with men (MSM). Sociodemographic characteristics and sexual behaviors were collected by using a structured questionnaire. Anal cytological results were examined, and HPV genotyping was performed by the Linear Array HPV Genotyping test. Logistic regression was used to estimate risk factors and their associations with high-risk HPV infection and cytological abnormalities. Among 163 MSM, 101 were seropositive for human immunodeficiency virus (HIV) and 62 were seronegative for HIV. The overall prevalence of HPV was 66.2%. A total of 61.9% and 48.2% of participants had never acquired any of either the quadrivalent or nonavalent vaccine HPV types, respectively. Cytological findings showed 15.3% atypical squamous cells of undetermined significance, 16.6% low-grade squamous intraepithelial lesion, 4.9% atypical squamous cells that cannot exclude high-grade squamous intraepithelial lesion and 17% high-grade squamous intraepithelial lesion. The number of high-risk HPV types was the predominant risk factor for abnormal anal cytology (OR 2.02, 95% CI 1.27-3.24). Infection with high-risk HPV was a significant predictor for cytological abnormality. MSM should be encouraged to obtain the HPV vaccine.

Distribution of virulence genes in bacteremic methicillin-resistant Staphylococcus aureus isolates from various sources.

BACKGROUND/PURPOSE: Methicillin-resistant Staphylococcus aureus (MRSA) can encode proteins which directly bind bacteria to many tissues and medical devices or catheters to trigger pathogenesis. However, the relationship between genetic backgrounds and virulent factors in MRSA isolates remained incompletely understood yet. METHODS: MRSA isolates were collected from blood cultures of patients with infective endocarditis, bone/joint infection, skin/soft tissue infection, or catheter-related bacteremia in hemodialysis at a tertiary medical center between 2005 and 2011. MRSA isolates were characterized by the methods of spa, multilocus sequence, and staphylococcal cassette chromosome mec (SCCmec) typing. Identification of virulence gene expression was measured by Power SYBR Green PCR Master Mix. RESULTS: Overall collected were 136 MRSA bacteremic isolates, including those from the cases of infective endocarditis (n = 23), bone/joint infection (n = 49), skin/soft tissue infection (n = 20), or catheter-related bacteremia in patients with acute kidney injury or end-stage renal stage receiving hemodialysis (n = 54). CC8-ST239-MRSA-SCCmec type III-spa type t037 was the most prevalent type observed in all of 136 MRSA bacteremic isolates. The prevalent genes in the group of infective endocarditis were clfA, clfB, fnbA, ebpS, eap, emp, sae, and eno; bone/joint infections clfA, emp, sae, and eno; skin/soft tissue infection eno; hemodialysis catheter-related bacteremia clfA and sae. The distribution of each gene was not statically different among four groups. CONCLUSIONS: A major MRSA lineage, CC8-ST239-MRSA-SCCmec type III-spa type t037, is noted among bacteremic MRSA isolates. No disease-specific virulent genes can be identified.

Clinical significance of human cytomegalovirus viruria and the effect of antiviral therapy in hematopoietic stem cell transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) causes life-threatening infections in immunocompromised host. The clinical significance of asymptomatic CMV viruria in patients receiving hematopoietic stem cell transplantation (HSCT) remains unclear. This study aims to clarify whether antiviral therapy is associated with a favorable clinical outcome. METHODS: HSCT recipients whose urine was culture-positive for CMV were retrospectively reviewed and followed. Viruria episodes were divided according to whether or not antiviral therapy was used. Mortality and the estimated glomerular filtration rate (eGFR) in 2 years following CMV viruria were compared between patients with and without antiviral therapy. RESULTS: Sixty-two episodes of culture-proven asymptomatic CMV viruria were identified in 28 HSCT recipients. Antiviral therapy was used in 35 (56.5%) and spared in 27 (43.5%) viruric episodes. Compared with the baselines, there were no significant difference in the decrements of eGFR between the two groups at the end the 1st year (4.78 vs 5.02 mL/min/1.73 m2, p = 0.968) and the 2nd year (1.13 vs 7.66 mL/min/1.73 m2, p = 0.276). Antiviral therapy for asymptomatic CMV viruria was also not associated with a favorable survival (p = 0.288). On the other hand, presence of CMV viremia correlated with a poorer survival (2-year mortality rate 60% vs 13.33%, p < 0.001). CONCLUSION: Antiviral therapy for asymptomatic CMV viruria is not associated with a clear clinical benefit in HSCT recipients. Further studies may be needed to identify if specific patient populations may benefit from antiviral therapy in CMV viruria.

Influenza vaccination and risk of respiratory failure in patients with chronic obstructive pulmonary disease: A nationwide population-based case-cohort study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease which causes a considerable disease burden. Patients with COPD are at a higher risk for influenza infection and influenza vaccination are recommended at this high risk patient group. In the current study, we aimed to evaluate the association between influenza vaccination and the risk of respiratory failure (RF) in COPD patients. METHODS: From 2001 to 2005, patients with newly diagnosed COPD were identified from the NHIRD, and were followed until 2010. We explored the influenza vaccination rate among this COPD cohort. Furthermore, patients who experienced RF were defined as case group, whereas the others were defined as control group. Baseline characteristic were compared and association between influenza vaccination and RF were evaluated. RESULTS: The rate of influenza vaccination was significantly higher in patients age ≥65 years than those age <65 years (54.8% vs. 4%, p < 0.001). The vaccine cohort had more comorbidities, more health care utilization and more frequent acute exacerbations as compared with nonvaccine cohort. In multivariable logistic regression, influenza vaccination was associated with a reduced risk of respiratory failure (adjusted odds ratio [aOR] 0.87, 95% confidence interval [CI] 0.79-0.96). In subgroup analysis, we found that the association was insignificant in patients age <65 years, patients with relatively unstable disease status and patient did not receive influenza vaccination annually. CONCLUSIONS: Influenza vaccination was associated with a decreased risk of RF in patients with COPD. Recommendation of annual influenza vaccination should be made when managing this high-risk patient group.

A phase 0 study of the pharmacokinetics, biodistribution, and dosimetry of 188Re-liposome in patients with metastatic tumors.

BACKGROUND: Liposomes are drug nano-carriers that are capable of targeting therapeutics to tumor sites because of enhanced permeability retention (EPR). In several preclinical studies with various tumor-bearing mice models, 188Re-liposome that has been developed by the Institute of Nuclear Energy Research (INER) demonstrates favorable in vivo tumor targeting, biodistribution, pharmacokinetics, and dosimetry. It inhibits the growth of tumors, increased survival, demonstrates good synergistic combination, and was safe to use. This study conducts a phase 0 low-radioactivity clinical trial of nano-targeted radiotherapeutics 188Re-liposome to evaluate the effectiveness with which it targets tumors and the pharmacokinetics, biodistribution, dosimetry, and its safety in use. Twelve patients with metastatic cancers are studied in this trial. Serial whole-body scans and SPECT/CT are taken at 1, 4, 8, 24, 48, and 72 h after intravenous injection of 111 MBq of 188Re-liposome. The effectiveness with which tumors are targeted, the pharmacokinetics, biodistribution, dosimetry, and safety are evaluated using the VelocityAI and OLINDA/EXM software. Blood samples are collected at different time points for a pharmacokinetics study and a safety evaluation that involves monitoring changes in liver, renal, and hematological functions. RESULTS: The T½z for 188Re-liposome in blood and plasma are 36.73 ± 14.00 h and 52.02 ± 45.21 h, respectively. The doses of radiation that are absorbed to vital organs such as the liver, spleen, lung, kidney, and bone marrow are 0.92 ± 0.35, 1.38 ± 1.81, 0.58 ± 0.28, 0.32 ± 0.09, and 0.06 ± 0.01 mGy/MBq, respectively, which is far less than the reference maximum tolerance dose after injection of 188Re-liposome. 188Re-liposome is absorbed by metastatic tumor lesions and the normal reticuloendothelial (RES) system. Certain patients exhibit a therapeutic response. CONCLUSION: This phase 0 exploratory IND study shows that nanocarrier 188Re-liposome achieves favorable tumor accumulation and tumor to normal organ uptake ratios for a subset of cancer patients. The clinical pharmacokinetic, biodistribution, and dosimetry results justify a further dose-escalating phase 1 clinical trial. TRIAL REGISTRATION: Taiwan FDA MA1101G0 (Jan 31, 2012).

Recommendations and guidelines for the treatment of pneumonia in Taiwan.

Pneumonia is a leading cause of death worldwide, ranking third both globally and in Taiwan. This guideline was prepared by the 2017 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, formed under the auspices of the Infectious Diseases Society of Taiwan (IDST). A consensus meeting was held jointly by the IDST, Taiwan Society of Pulmonary and Critical Care Medicine (TSPCCM), the Medical Foundation in Memory of Dr. Deh-Lin Cheng, the Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines. The final guideline was endorsed by the IDST and TSPCCM. The major differences between this guideline and the 2007 version include the following: the use of GRADE methodology for the evaluation of available evidence whenever applicable, the specific inclusion of healthcare-associated pneumonia as a category due to the unique medical system in Taiwan and inclusion of recommendations for treatment of pediatric pneumonia. This guideline includes the epidemiology and recommendations of antimicrobial treatment of community-acquired pneumonia, hospital-acquired pneumonia, ventilator-associated pneumonia, healthcare-associated pneumonia in adults and pediatric pneumonia.

Biodistribution, Pharmacokinetics and Efficacy of 188Re(I)-Tricarbonyl-Labeled Human Serum Albumin Microspheres in an Orthotopic Hepatoma Rat Model.

BACKGROUND/AIM: The biodistribution, pharmacokinetics and therapeutic evaluation of 188Re-human serum albumin microspheres (188Re-HSAM) by labeling with 188Re(I)-tricarbonyl ion (188Re(OH2)3(CO)3)+) were investigated in a GP7TB orthotopic hepatoma rat model. MATERIALS AND METHODS: Male F344 rats received intrahepatic inoculations with GP7TB 1 mm3 cubes. The efficacy of 188Re-HSAM was examined following a single-dose treatment via the intraarterial route. Rats were monitored for survival until death. RESULTS: The labeling efficiency of the 188Re-HSAM was about 80%. After intraarterial administration of 188Re-HSAM, radioactivity in tumors accumulated from 18.41±3.48 %ID/g at 1 h to 12.43±4.70 %ID/g at 24 h. The tumor/liver ratios ranged from 3.03 at 1 h to 1.89 at 72 h. The major uptake organs of 188Re-HSAM were liver (73.35%ID to 48.92%ID), tumor (10.54%ID to 3.51%ID) and kidney (7.48 %ID to 0.14%ID). The T1/2λz of 188Re-HSAM was 259.34 h after intraarterial injection. The AUC(0→96 h) of 188Re-HSAM was 0.69 h*% ID/g. In the efficacy study, the median survival time for the rat (n=6), that received normal saline was 80 d. The median survival times for the mice treated with 10 mCi (n=4), 5.2 mCi (n=6) and 2.9 mCi (n=3) of 188Re-HSAM were 130 d (p=0.003), 106 d (p=0.002) and 83.5 d (p=0.617), respectively. The increase in life span of 10 mCi, 5.2 mCi and 2.9 mCi of 188Re-HSAM were 62.5%, 32.5% and 4.4%, respectively. CONCLUSION: Administration of 188Re-HSAM demonstrated better survival time and therapeutic efficacy at the higher dose in the GP7TB hepatoma model. These results suggested that intraarterial administration of 188Re-HSAM could provide a benefit and promising strategy for delivery of radiotherapeutics in oncology applications.