Unfractionated heparin infusion for treatment of venous thromboembolism based on actual body weight without dose capping.

Controversy exists regarding the use of dose capping of weight-based unfractionated heparin (UFH) infusions in obese and morbidly obese patients. The primary objective of this study was to compare time to first therapeutic activated partial thromboplastin time (aPTT) in hospitalized patients receiving UFH for acute venous thromboembolism (VTE) among three body mass index (BMI) cohorts: non-obese (< 30 kg/m2), obese (30-39.9 kg/m2), and morbidly obese (⩾ 40 kg/m2). In this single-center, retrospective cohort study, patients were included if they ⩾ 18 years of age, had a documented VTE, and were on an infusion of UFH for at least 24 hours. Weight-based UFH doses were calculated using actual body weight. A total of 423 patients met the inclusion criteria, with 230 (54.4%), 146 (34.5%), and 47 (11.1%) patients in the non-obese, obese, and morbidly obese cohorts, respectively. Median times to therapeutic aPTT were 16.4, 16.6, and 17.1 hours in each cohort. Within 24 hours, the cumulative incidence rates for therapeutic aPTT were 70.7% for the non-obese group, 69.9% for the obese group, and 61.7% for the morbidly obese group (obese vs non-obese: HR = 1.02, 95% CI: 0.82-1.26, p = 0.88; morbidly obese vs non-obese: HR = 0.87, 95% CI: 0.62-1.21, p = 0.41). There was no significant difference in major bleeding events between BMI groups (obese vs non-obese, p = 0.91; morbidly obese vs non-obese, p = 0.98). Based on our study, heparin dosing based on actual body weight without a dose cap is safe and effective.

Comparison of In-Hospital Bleeding and Cardiovascular Events with High-Dose Bolus Tirofiban and Shortened Infusion to Short-Duration Eptifibatide as Adjunctive Therapy for Percutaneous Coronary Intervention.

Potent platelet inhibition is one of the most important medical interventions to prevent ischemic complications during and after percutaneous coronary intervention (PCI). Practice has evolved with the introduction of potent oral P2Y12 inhibitors that provide quick, effective platelet inhibition, and the need for routine glycoprotein IIb/IIIa inhibitors (GPIs) has decreased. Additionally, a shorter duration of GPI infusion has been shown to be safe with adequate oral antiplatelet loading, but clinical outcome data are limited to eptifibatide. This single-center, retrospective cohort study analyzed in-hospital outcomes for patients who received adjunctive GPI therapy for PCI before and after an institution-wide switch to high-dose bolus tirofiban with shortened infusion from short-duration eptifibatide. The primary end point was a composite in-hospital outcome of major and minor bleeding and cardiovascular events (death, myocardial infarction, coronary artery bypass grafting, ischemic stroke, and target vessel revascularization). Secondary end points included bleeding and cardiovascular event types. A total of 357 and 446 patients received eptifibatide and tirofiban, respectively, from February 1, 2014 through September 30, 2017. Thirty five eptifibatide and 46 tirofiban patients experienced an in-hospital composite event (9.8% vs 10.3%, p = 0.81). There was no difference found between in-hospital bleeding (6.4% vs 5.4%, p = 0.52) or cardiovascular events (5.6% vs 6.5%, p = 0.60) with the use of eptifibatide or tirofiban, respectively. Multivariable analysis showed that patients with transradial access or an indication of unstable angina were less likely to experience an in-hospital composite event (OR 0.30 and 0.19, respectively, p <0.001 for both). In conclusion, the use of high-dose bolus tirofiban with shortened infusion versus short-duration eptifibatide was not associated with an increase of in-hospital bleeding or cardiovascular events.

Early Diuresis After Colon and Rectal Surgery Does Not Reduce Length of Hospital Stay: Results of a Randomized Trial.

BACKGROUND: Excessive perioperative fluid administration likely increases postoperative cardiovascular, infectious, and GI complications. Early administration of diuretics after elective surgery facilitates rapid mobilization of excess fluid, potentially leading to decreased bowel edema, more rapid return of bowel function, and reduced length of hospital stay. OBJECTIVE: This study aimed to evaluate the benefit of early diuresis after elective colon and rectal surgery in the setting of an enhanced recovery after surgery practice. DESIGN: This was a prospective study. SETTINGS: The study was conducted at a quaternary referral center. PATIENTS: A randomized, open-label, parallel-group trial was conducted in patients undergoing elective colon and rectal surgery at a single quaternary referral center. INTERVENTION: The primary intervention was administration of intravenous furosemide plus enhanced recovery after surgery on postoperative day 1 and 2 versus enhanced recovery after surgery alone. MAIN OUTCOME MEASURES: The primary outcome was length of hospital stay. Secondary outcomes included 30-day readmission rate, time to stool output during hospitalization after surgery, and incidence of various complications within the first 48 hours of hospital stay. RESULTS: In total, 123 patients were randomly assigned to receive either furosemide plus enhanced recovery after surgery (n = 62) or enhanced recovery after surgery alone (n = 61). Groups were evenly matched at baseline. At interim analysis, length of hospital stay was not superior in the intervention group (80.6 vs 99.6 hours, p = 0.564). No significant difference was identified in the rates of nasogastric tube replacement (1.6% vs 9.7%, p = 0.125). Time to return of bowel function was significantly longer in the intervention group (45.4 vs 48.8 hours, p = 0.048). The decision was made to end the study early because the conditional power of the study favored futility. LIMITATIONS: This was a single-center study. CONCLUSIONS: Early administration of furosemide does not significantly reduce the length of hospital stay after elective colon and rectal surgery in the setting of enhanced recovery after surgery practice. See Video Abstract at http://links.lww.com/DCR/A714.

Electricity-free amplification and detection for molecular point-of-care diagnosis of HIV-1.

In resource-limited settings, the lack of decentralized molecular diagnostic testing and sparse access to centralized medical facilities can present a critical barrier to timely diagnosis, treatment, and subsequent control and elimination of infectious diseases. Isothermal nucleic acid amplification methods, including reverse transcription loop-mediated isothermal amplification (RT-LAMP), are well-suited for decentralized point-of-care molecular testing in minimal infrastructure laboratories since they significantly reduce the complexity of equipment and power requirements. Despite reduced complexity, however, there is still a need for a constant heat source to enable isothermal nucleic acid amplification. This requirement poses significant challenges for laboratories in developing countries where electricity is often unreliable or unavailable. To address this need, we previously developed a low-cost, electricity-free heater using an exothermic reaction thermally coupled with a phase change material. This heater achieved acceptable performance, but exhibited considerable variability. Furthermore, as an enabling technology, the heater was an incomplete diagnostic solution. Here we describe a more precise, affordable, and robust heater design with thermal standard deviation <0.5°C at operating temperature, a cost of approximately US$.06 per test for heater reaction materials, and an ambient temperature operating range from 16°C to 30°C. We also pair the heater with nucleic acid lateral flow (NALF)-detection for a visual readout. To further illustrate the utility of the electricity-free heater and NALF-detection platform, we demonstrate sensitive and repeatable detection of HIV-1 with a ß-actin positive internal amplification control from processed sample to result in less than 80 minutes. Together, these elements are building blocks for an electricity-free platform capable of isothermal amplification and detection of a variety of pathogens.

A Rapid, Multiplexed, High-Throughput Flow-Through Membrane Immunoassay: A Convenient Alternative to ELISA.

This paper describes a rapid, high-throughput flow-through membrane immunoassay (FMIA) platform. A nitrocellulose membrane was spotted in an array format with multiple capture and control reagents for each sample detection area, and assay steps were carried out by sequential aspiration of sample and reagents through each detection area using a 96-well vacuum manifold. The FMIA provides an alternate assay format with several advantages over ELISA. The high surface area of the membrane permits high label concentration using gold labels, and the small pores and vacuum control provide rapid diffusion to reduce total assay time to ~30 min. All reagents used in the FMIA are compatible with dry storage without refrigeration. The results appear as colored spots on the membrane that can be quantified using a flatbed scanner. We demonstrate the platform for detection of IgM specific to lipopolysaccharides (LPS) derived from Salmonella Typhi. The FMIA format provides analytical results comparable to ELISA in less time, provides integrated assay controls, and allows compensation for specimen-to-specimen variability in background, which is a particular challenge for IgM assays.

Microfluidics without pumps: reinventing the T-sensor and H-filter in paper networks.

Conventional microfluidic devices typically require highly precise pumps or pneumatic control systems, which add considerable cost and the requirement for power. These restrictions have limited the adoption of microfluidic technologies for point-of-care applications. Paper networks provide an extremely low-cost and pumpless alternative to conventional microfluidic devices by generating fluid transport through capillarity. We revisit well-known microfluidic devices for hydrodynamic focusing, sized-based extraction of molecules from complex mixtures, micromixing, and dilution, and demonstrate that paper-based devices can replace their expensive conventional microfluidic counterparts.

Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma.

PURPOSE: Radioimmunotherapy has been approved for relapsed follicular lymphoma (FL), including rituximab-refractory FL. This study was designed to determine the CR rate with short-course chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (CHOP-R) followed by 90-Y ibritumomab tiuxetan (RIT) with extended rituximab as first-line treatment. EXPERIMENTAL DESIGN: Between March 2004 and February 2007, 60 patients with stage II to IV symptomatic or bulky FL from a single institution supported by a large community network entered this phase II trial. Patients received CHOP-R for three treatment cycles before RIT followed by four additional weekly treatments with rituximab. Response was determined using fusion [(18) F] fluorodeoxyglucose-positron emission tomography (PET)-computed tomography (CT) imaging. RESULTS: Of the 60 patients entering this trial, 55 patients completed all protocol therapy. The median follow up was 19.7 months (range, 0.26-35.9 months). For intent-to-treat analysis, the complete response (CR) rate after CHOP-R, as assessed by CT and PET imaging, was 40% and 46%, respectively. After RIT, the CR rate improved, as assessed by CT and PET imaging, to 82% and 89%, respectively. Ten patients have progressed, including eight from best response of CR. Seven of 18 patients who were PET positive after CHOP-R progressed compared with 3 of 37 patients who were PET negative (P=0.010). CONCLUSIONS: In patients with previously untreated, symptomatic or bulky FL, short-course chemoimmunotherapy and consolidation RIT and extended rituximab resulted in a high CR rate. Failure to achieve an early PET CR after CHOP-R indicated high risk of relapse.

Enabling a microfluidic immunoassay for the developing world by integration of on-card dry reagent storage.

As part of an effort to create a point-of-care diagnostic system for the developing world, we present a microfluidic flow-through membrane immunoassay with on-card dry reagent storage. By preserving reagent function, the storage and reconstitution of anhydrous reagents enables the devices to remain viable in challenging, unregulated environmental conditions. The assay takes place on a disposable laminate card containing both a porous membrane patterned with capture molecules and a fibrous pad containing an anhydrous analyte label. To conduct the assay, the card is placed in an external pumping and imaging instrument capable of delivering sample and rehydrated reagent to the assay membrane at controlled flow rates to generate quantitative results. Using the malarial antigen Plasmodium falciparum histidine-rich protein II (PfHRP2) as a model, we demonstrate selection of dry storage conditions, characterization of reagent rehydration, and execution of an automated on-card assay. Gold-antibody conjugates dried in a variety of sugar matrices were shown to retain 80-96% of their activity after 60 days of storage at elevated temperatures, and the release profile of the reconstituted reagent was characterized under flow in microfluidic channels. The system gave a detection limit in the sub-nanomolar range in under nine minutes, showing the potential to expand into quantitative, multi-analyte analysis of human blood samples.

Direct multiplexed measurement of gene expression with color-coded probe pairs.

We describe a technology, the NanoString nCounter gene expression system, which captures and counts individual mRNA transcripts. Advantages over existing platforms include direct measurement of mRNA expression levels without enzymatic reactions or bias, sensitivity coupled with high multiplex capability, and digital readout. Experiments performed on 509 human genes yielded a replicate correlation coefficient of 0.999, a detection limit between 0.1 fM and 0.5 fM, and a linear dynamic range of over 500-fold. Comparison of the NanoString nCounter gene expression system with microarrays and TaqMan PCR demonstrated that the nCounter system is more sensitive than microarrays and similar in sensitivity to real-time PCR. Finally, a comparison of transcript levels for 21 genes across seven samples measured by the nCounter system and SYBR Green real-time PCR demonstrated similar patterns of gene expression at all transcript levels.