Abstract In the ENSURE-AF study (NCT 02072434), edoxaban was compared to enoxaparin–warfarin in 2199 patients undergoing electrical cardioversion of non-valvular atrial fibrillation (AF). In this ...multicenter PROBE trial, we analyzed patients randomized to enoxaparin–warfarin. We determined time to achieve therapeutic range (TtTR), time in therapeutic range (TiTR), their clinical determinants, relation to SAMe-TT2 R2 score, and impact on primary endpoints (composite of stroke, systemic embolic event SEE, myocardial infarction MI, and cardiovascular death CVD and composite of major + clinically relevant non-major CRNM bleeding). Among 1104 patients randomized to enoxaparin––warfarin, 27% were oral anticoagulant naïve. Mean age was 64.2±11 years and mean CHA2 DS2 -VASc score was 2.6. Mean TtTR was 7.7 days (median 7 days) and mean TiTR after reaching INR 2.0–3.0 was 71%. In 695 patients with INR <2.0 prior to first dose and who reached ≥2.0, 436 had a SAMe-TT2 R2 score ≤2 and 259 a score of >2. On multivariate regression, an independent predictor of extended TtTR was creatinine clearance (CrCl) P =0.02. TtTR was marginally related to stroke/SEE/MI/CVD ( P =0.06; OR=0.23, 95% CI 0.02–1.17) but not to any bleeding. Independent predictors of TiTR were prior VKA experience ( P <0.01) and low HAS-BLED score ( P =0.02). TiTR was related to any bleeding ( P =0.02; OR=0.39, 95% CI 0.16–0.88), but not stroke/SE/MI/CVD. In this cohort of warfarin users with a high TiTR no difference was seen between TtTR and TiTR in relation to SAMe-TT2 R2 score. In conclusion, even in this short-term study, TiTR was significantly related to bleeding events.
Abstract Background The New Rural Cooperative Medical Scheme (NRCMS) covers 900 million farmers (about 95%) in China, but its fund is at serious risk of deficit. Shanghai, one of the developed cities ...in China, has developed its Rural Cooperative Medical Scheme and NRCMS as an advanced and exemplary representative of Chinese rural health insurance. The participating rate of NRCMS was 99·90% in Pudong New Area in 2015, which meant 277 310 farmers were involved, accounting for 29% of Shanghai's participants. Pudong New Area of Shanghai implemented NRCMS capitation reform in August, 2012, aimed at controlling the increasing medical costs for farmers and avoid risk to the NRCMS's fund. We aimed to assess long-term effect of the reform. Methods We performed a retrospective time series analysis of the NRCMS fund by examining data acquired from Jan 1, 2011, until Dec 31, 2015 (60 months), in Pudong. The analysis was based on time series data modelling before Aug 1, 2012, and we compared forecast data produced with Winters' additive models and with simple seasonal models with observed data for the 40 months after capitation reform. Outcome measurements included numbers and costs of insured outpatients and inpatients. Findings The mean forecasted outpatient cost per visit (¥102·00, mean absolute percentage error MAPE 2·9%) and inpatient cost (¥12 836·63, 1·9%) by Winters' additive models were both higher than observed values (outpatient cost ¥90·37, p<0·0001; inpatient: ¥11 176·95, p<0·001). However, visit forecasts based on simple seasonal models did not differ from observed monthly visits (predicted outpatient visits 511 550 vs actual visits 486 976, p=0·121; predicted inpatient visits 2173 vs actual visits 2147, p=0·74). NRCMS fund surplus rate was 8·84% in 2015, which was 6·93 percentage points higher than it was in 2011. Interpretation Capitation reform led to declines in per outpatient and inpatient costs, while the medical need remained unchanged. Furthermore, the increased surplus rate ensured the fund's security. Funding National Nature Science Foundation of China (#71503170; for data interpretation), Shanghai Municipal Commission of Health and Family Planning (#201440036, #2016HP009; for data collection and analysis).
Parasite infestation is still associated with significant morbidity and mortality. Hookworm infestation is a very rare cause of pancreatitis. This parasitic infestation might be asymptomatic. Acute ...pancreatitis as a result of the hookworms migrating into the ampulla of Vater with chronic inflammation was a very rare complication. Were port a case of hookworm infestation that was associated with significant complication of recurrent pancreatitis. The patient was treated with mebendazole. He was asymptomatic and had gained weight at the 3-month follow-up. Our case demonstrates that pancreatitis secondary to hookworm infection can occur and may resolve after anthelmintic treatment.
Cerebral venous sinus thrombosis (CVST) has become a rare but potentially life-threatening condition in perinatal women. Early and rapid identification of CVST in pregnant women is a challenge for ...frontline clinical workers. In this study, 40 perinatal patients with CVST in our hospital were included in the five-year period, and 120 normal perinatal pregnant women in the obstetrics and gynecology department of our hospital were randomly enrolled in the five-year period as the control group, including 60 cases in pregnancy and puerperium. 5 mL of fasting venous blood was collected from puerperal CVST patients in the acute phase of onset (within 72 h of onset) and the recovery phase (fourth week of treatment). In the control group, 5 mL of fasting venous blood was collected. Coagulation factors X, XI, and XII, plasma D-Dimer were analyzed and compared. Coagulation factors X, XI, and XII in plasma of CVST patients were significantly increased compared with controls. Plasma coagulation factors X, XI, and XII and their combined detection (Union Model = 0.056 * FX: C + 0.046 * FXI: C + 0.081 * FXII: C) have diagnostic values for perinatal CVST. Plasma coagulation factors X, XI, and XII were significantly positively correlated with plasma D-dimer levels in perinatal CVST patients. Plasma coagulation factors X, XI, and XII have diagnostic values for perinatal CVST.
Abstract Background Only four cases of primary intracerebellar paragangliomas have been reported in the literature to date. Because of its rarity, primary intracerebellar paraganglioma still presents ...a diagnostic challenge for both radiologists and neurosurgeons, and the optimal therapeutic modality is still debatable for its hypervascularity and location. Patients We report a 16-year-old boy with pathology-proven primary intracerebellar paraganglioma who presented with dull headache, dizziness, and gait disturbance, and underwent gross total resection. Further, we review all reported cases of primary intracerebellar paraganglioma in the English literature and discuss its clinical profile, neuroradiological features, and treatment modalities. Results His symptoms improved following tumor removal without radiotherapy, and postoperative neuroimaging thirteenth months after surgery showed no recurrence. In the literature, all four patients were stable in the follow-up period including three with complete resection and one with partial resection plus adjuvant radiotherapy. Conclusion Surgical resection is the treatment modality most often used for primary intracerebellar paraganglioma; radiation therapy may be used when there is residual tumor or recurrence. Angiography may help to clarify the vessel architecture for reducing intraoperative bleeding when primary intracerebellar paraganglioma is considered.
Cancer patients are at high risk of developing venous thromboembolism (VTE). The risk of VTE could be mitigated with the administration of prophylactic anticoagulants. Therefore, risk assessment ...models would be a useful tool in order to identify those patients who are at higher risk and will be benefited more by prophylactic anticoagulants. This study retrospectively examined 528 newly diagnosed colorectal cancer patients from January 2019 to January 2021. Specified logistic regression models were employed to screen the factors and establish prediction tools based on nomograms according to the final included variables. Discrimination, calibration, and clinical applicability were used to assess the performance of screening tools. In addition, internal verifications were conducted through 10-fold cross-verification, leave-one-out cross-validation, and Bootstrap verification. Four risk factors, closely related to the occurrence of VTE in colorectal cancer patients, were identified after univariate and multivariate logistic regression, including age, body mass index, activated partial thromboplastin time, and D-Dimer value. Besides, the risk assessment model named ABAD was built on the basis, displaying good discriminations and calibrations. The area under the curve was 0.705 (95% confidence interval CI, 0.644 to 0.766). According to Hosmer–Lemeshow goodness-of-fit test, a good agreement between the predicted and observed VTE events in patients with newly-diagnosed gastrointestinal cancer was observed for χ2 = 6.864, P = .551. Internal validation was applied with a C-index of 0.669 in the 10-fold cross-verification, 0.658 in the leave-one-out cross verification and 0.684 in the bootstrap verification. We developed a prediction model called ABAD for newly diagnosed colorectal cancer patients, which can be used to predict the risk of VTE. After evaluation and internal verification, we believe that ABAD exhibited high predictive performance and availability and could be recommended.
Background: Pancreatic cancer is a difficult-to-treat cancer with a late presentation and poor prognosis. Some patients seek traditional Chinese medicine (TCM) consultation. We aimed to investigate ...the benefits of complementary Chinese herbal medicine (CHM) among patients with pancreatic cancer in Taiwan. Methods: We included all patients with pancreatic cancer who were registered in the Taiwanese Registry for Catastrophic Illness Patients Database between 1997 and 2010. We used 1:1 frequency matching by age, sex, the initial diagnostic year of pancreatic cancer, and index year to enroll 386 CHM users and 386 non-CHM users. A Cox regression model was used to compare the hazard ratios (HRs) of the risk of mortality. The Kaplan-Meier curve was used to compare the difference in survival time. Results: According to the Cox hazard ratio model mutually adjusted for CHM use, age, sex, urbanization level, comorbidity, and treatments, we found that CHM users had a lower hazard ratio of mortality risk (adjusted HR = 0.67, 95% CI = 0.56-0.79). Those who received CHM therapy for more than 90 days had significantly lower hazard ratios of mortality risk than non-CHM users (90- to 180-day group: adjusted HR = 0.56, 95% CI = 0.42-0.75; >180-day group: HR = 0.33, 95% CI = 0.24-0.45). The survival probability was higher for patients in the CHM group. Bai-hua-she-she-cao (Herba Oldenlandiae; Hedyotis diffusa Spreng) and Xiang-sha-liu-jun-zi-tang (Costus and Chinese Amomum Combination) were the most commonly used single herb and Chinese herbal formula, respectively. Conclusions: Complementary Chinese herbal therapy might be associated with reduced mortality among patients with pancreatic cancer. Further prospective clinical trial is warranted.
Although geriatric syndromes have been studied extensively, their interactions with one another and their accumulated effects on life expectancy are less frequently discussed. This study examined ...whether geriatric syndromes and their cumulative effects are associated with risks of mortality in community-dwelling older adults.
Data were collected from the Taiwan Longitudinal Study in Aging in 2003, and the participant survival status was followed until December 31, 2007. A total of 2744 participants aged ≥65 years were included in this retrospective cohort study; 634 died during follow-up. Demographic factors, comorbidities, health behaviors, and geriatric syndromes, including underweight, falls, functional impairment, depressive condition, and cognitive impairment, were assessed. Cox proportional hazard regression analysis was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the probability of survival according to the cumulative number of geriatric syndromes.
The prevalence of geriatric syndromes increased with age. Mortality was significantly associated with age ≥75 years; male sex; ≤6 years of education; history of stroke, malignancy; smoking; not drinking alcohol; and not exercising regularly. Geriatric syndromes, such as underweight, functional disability, and depressive condition, contributed to the risk of mortality. The accumulative model of geriatric syndromes also predicted higher risks of mortality (N = 1, HR 1.50, 95% CI 1.19-1.89; N = 2, HR 1.69, 95% CI 1.25-2.29; N ≥ 3, HR 2.43, 95% CI 1.62-3.66).
Community-dwelling older adults who were male, illiterate, receiving institutional care, underweight, experiencing a depressive condition, functionally impaired, and engaging in poor health behavior were more likely to have a higher risk of mortality. The identification of geriatric syndromes might help to improve comprehensive care for community-dwelling older adults.
While the search for an efficacious HIV-1 vaccine remains elusive, emergence of a new generation of virus-neutralizing monoclonal antibodies (mAbs) has re-ignited the field of passive immunization ...for HIV-1 prevention. However, the plasticity of HIV-1 demands additional improvements to these mAbs to better ensure their clinical utility. Here, we report engineered bispecific antibodies that are the most potent and broad HIV-neutralizing antibodies to date. One bispecific antibody, 10E8V2.0/iMab, neutralized 118 HIV-1 pseudotyped viruses tested with a mean 50% inhibitory concentration (IC50) of 0.002 μg/mL. 10E8V2.0/iMab also potently neutralized 99% of viruses in a second panel of 200 HIV-1 isolates belonging to clade C, the dominant subtype accounting for ∼50% of new infections worldwide. Importantly, 10E8V2.0/iMab reduced virus load substantially in HIV-1-infected humanized mice and also provided complete protection when administered prior to virus challenge. These bispecific antibodies hold promise as novel prophylactic and/or therapeutic agents in the fight against HIV-1.
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•We engineered bispecific antibodies with exquisite potency and breadth against HIV-1•Two bispecifics are the most potent and broad HIV-neutralizing antibodies to date•One bispecific inhibited HIV-1 in HIV treatment and HIV prevention animal models•These bispecifics are novel clinical candidates for HIV prevention and treatment
Monotherapy with bispecific engineered antibodies, which have the broadest and most potent neutralizing activity against HIV-1 described to date, can neutralize HIV-1 in both prevention and treatment animal models.
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