The delivery of drugs in a controllable fashion is a topic of intense research activity in both academia and industry because of its impact in healthcare. Implantable electronic interfaces for the ...body have great potential for positive economic, health, and societal impacts; however, the implantation of such interfaces results in inflammatory responses due to a mechanical mismatch between the inorganic substrate and soft tissue, and also results in the potential for microbial infection during complex surgical procedures. Here, we report the use of conducting polypyrrole (PPY)-based coatings loaded with clinically relevant drugs (either an anti-inflammatory, dexamethasone phosphate (DMP), or an antibiotic, meropenem (MER)). The films were characterized and were shown to enhance the delivery of the drugs upon the application of an electrochemical stimulus in vitro, by circa (ca.) 10⁻30% relative to the passive release from non-stimulated samples. Interestingly, the loading and release of the drugs was correlated with the physical descriptors of the drugs. In the long term, such materials have the potential for application to the surfaces of medical devices to diminish adverse reactions to their implantation in vivo.
Micro RNAs (miRNAs) have shown great potential as rapid and discriminating biomarkers for acute myocardial infarction (AMI) diagnosis. We have developed a multiplexed ion-exchange membrane-based ...miRNA (MIX·miR) preconcentration/sensing amplification-free platform for quantifying in parallel a panel of miRNAs, including miR-1, miR-208b, and miR-499, from the same plasma samples from: 1) reference subjects with no evident coronary artery disease (NCAD); 2) subjects with stable coronary artery disease (CAD); and 3) subjects experiencing ST-elevation myocardial infarction (STEMI) prior to (STEMI-pre) and following (STEMI-PCI) percutaneous coronary intervention. The picomolar limit of detection from raw plasma and 3-decade dynamic range of MIX·miR permits detection of the miRNA panel in untreated samples from disease patients and its precise standard curve, provided by large 0.1 to 1 V signals and eliminates individual sensor calibration. The use of molecular concentration feature reduces the assay time to less than 30 minutes and increases the detection sensitivity by bringing all targets close to the sensors. miR-1 was low for NCAD patients but more than one order of magnitude above the normal value for all samples from three categories (CAD, STEMI-pre, and STEMI-PCI) of patients with CAD. In fact, miR-1 expression levels of stable CAD, STEMI-pre and STEMI-PCI are each more than 10-fold higher than the previous class, in that order, well above the 95% confidence level of MIX·miR. Its overexpression estimate is significantly higher than the PCR benchmark. This suggests that, in contrast to protein biomarkers of myocardial injury, miR-1 appears to differentiate ischemia from both reperfusion injury and non-AMI CAD patients. The battery-operated MIX·miR can be a portable and low-cost AMI diagnostic device, particularly useful in settings where cardiac catheterization is not readily available to determine the status of coronary reperfusion.
This work reports a multiplexed ion-exchange membrane-based miRNA sensor, namely MIX·miR, for detection of multiple specific cardiac-associated exosomal miRNA markers in clinical plasma samples with concentrations as low as 1 pM.
Key Clinical Message
While intermittent hemodialysis (HD) is the most efficient method of removing lithium in patients with lithium toxicity, continuous renal replacement therapy is an acceptable ...alternative in the setting of intradialytic hypotension. This form of dialysis can reduce the need for vasopressors during HD, which increases mortality.
Abstract Introduction Actinomyces naeslundii has been recovered from traumatized permanent teeth diagnosed with necrotic pulps. In this work, a triple antibiotic paste (TAP)–mimic scaffold is ...proposed as a drug-delivery strategy to eliminate A. naeslundii dentin biofilm. Methods Metronidazole, ciprofloxacin, and minocycline were added to a polydioxanone (PDS) polymer solution and spun into fibrous scaffolds. Fiber morphology, mechanical properties, and drug release were investigated by using scanning electron microscopy, microtensile testing, and high-performance liquid chromatography, respectively. Human dentin specimens (4 × 4 × 1 mm3 , n = 4/group) were inoculated with A. naeslundii (ATCC 43146) for 7 days for biofilm formation. The infected dentin specimens were exposed to TAP-mimic scaffolds, TAP solution (positive control), and pure PDS (drug-free scaffold). Dentin infected (7-day biofilm) specimens were used for comparison (negative control). Confocal laser scanning microscopy was done to determine bacterial viability. Results Scaffolds displayed a submicron mean fiber diameter (PDS = 689 ± 312 nm and TAP-mimic = 718 ± 125 nm). Overall, TAP-mimic scaffolds showed significantly ( P ≤ .040) lower mechanical properties than PDS. Within the first 24 hours, a burst release for all drugs was seen. A sustained maintenance of metronidazole and ciprofloxacin was observed over 4 weeks, but not for minocycline. Confocal laser scanning microscopy demonstrated complete elimination of all viable bacteria exposed to the TAP solution. Meanwhile, TAP-mimic scaffolds led to a significant ( P < .05) reduction in the percentage of viable bacteria compared with the negative control and PDS. Conclusions Our findings suggest that TAP-mimic scaffolds hold significant potential in the eradication/elimination of bacterial biofilm, a critical step in regenerative endodontics.
Nitrofurantoin has been utilized for the prevention and treatment of urinary tract infections (UTIs) since the 1950s, and it has been prescribed with increasing frequency since being recommended as a ...first-line therapy. The adverse neurological and psychiatric effects of antibiotic medications have been well-established. There is evidence to suggest a direct association between acute psychosis and antibiotic exposures. Nitrofurantoin-induced adverse effects have been reported recurrently; however, to the best of our knowledge, a combination of auditory and visual hallucinations with normal baseline mentation and cognition in an immunocompetent geriatric patient, without previously reported hallucinations, have not been reported in the literature so far. We present a case of an 86-year-old Caucasian female who was admitted with audio and visual hallucinations on the fifth day of starting nitrofurantoin therapy for UTI. During her stay, after ruling out all other probable etiologies, it was determined that the likely pathogenesis of the patient's neuropsychiatric effects was the use of nitrofurantoin.
Implantable pacemakers have been the mainstay of therapy for patients with severely decreased left ventricular ejection fractions and recurrent arrhythmias, among other cardiac pathology. Twiddler's ...syndrome (TS) is an uncommon but potentially life-threatening complication of pacemaker therapy, defined as pacemaker malfunction in the setting of device lead dislodgment due to physical manipulation. Traditionally, there are three distinct TS variants (reeling, ratchet and coiling). This case offers evidence of a unique and new variant of TS, severe recurrent erosive subtype with pacemaker externalization.
In New Zealand, trastuzumab is standard therapy for human epidermal growth factor receptor-2 (HER2)-positive early and metastatic breast cancer. Given the requirement for ongoing adjuvant or ...maintenance treatment and intravenous (IV) delivery, such a regimen consumes considerable health care resources. The development of a subcutaneous (SC) trastuzumab formulation with a short administration time offers the potential to reduce hospital expenditure. The aim of this study was to determine medical resource utilization associated with administration of trastuzumab SC injection via handheld syringe vs trastuzumab IV infusion in patients with HER2-positive breast cancer in New Zealand.
This noninterventional, descriptive study was conducted at the outpatient oncology centers at Auckland City and Tauranga Hospitals. Trained observers recorded times associated with health care professional (HCP) tasks and consumables use associated with preparation and administration of trastuzumab IV or SC in women with early or metastatic breast cancer. The cost for each formulation was calculated as the mean cost of HCP time (based on Pharmaceutical Management Agency hourly rates) plus the mean cost of consumables used.
Use of trastuzumab SC vs IV reduced mean chair time by 36.95 minutes and total nurse time by 6.12 minutes; there was a 20.45-minute reduction in pharmacist time when the SC formulation was used. After adding consumable costs, the overall estimated saving with trastuzumab SC vs IV was $76.94 (New Zealand dollars) per patient per cycle.
Compared with trastuzumab IV infusion, administration of trastuzumab via SC injection reduced time spent in the clinic and decreased HCP resources and consumables needed to administer treatment. These reductions could contribute to a decrease in health care costs and an improvement in the efficiency of HER2-positive breast cancer treatment delivery.
Background
Well-conducted, investigator-led randomized controlled trials (RCTs) are the gold standard for evaluating the efficacy of new treatments and are a key component of evidence-based medicine. ...It is unclear whether participating in an RCT is beneficial to the individual before the results of RCTs are known.
Purpose
In a matched historical cohort study, we examined whether participation in RCTs was associated with improved health outcomes.
Methods
Participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE), Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET), or Telmisartan Randomized Assessment Study in ACE-intolerant Subjects with Cardiovascular Disease (TRANSCEND) studies and non-participant controls were selected from patients attending outpatient clinics at Middlemore Hospital between 2001 and 2003.
Results
A total of 251 RCT participants and 502 randomly selected patients not enrolled in a trial but who met study entry criteria were matched for age, gender, and ethnicity. There was a significant difference in all-cause mortality for trial participants versus non-participants over the study period (unadjusted relative risk reduction (RRR) = 63%; 95% confidence interval (CI) = 28%–81%) and a significant reduction in cardiovascular mortality (unadjusted RRR = 81%; 95% CI = 17%–95%) favouring RCT participants. Allowing for co-morbidity, the adjusted RRR of all-cause mortality associated with trial participation was 55% (95% CI = 10%–77%). Active treatment in an RCT was found to be less explanatory than trial participation. The adjusted RRR for cardiovascular mortality associated with active treatment in a trial was 86% (95% CI = −2% to 98%), with trial participation found to be less explanatory than active treatment.
Limitations
The main limitations of this trial relate to its design as a retrospective study with a historical cohort comparison group. Limitations include lack of complete data for some patients, bias in selection of the comparison group, and the effects of confounding variables. However, the study design and analysis were planned so as to minimize these as much as possible.
Conclusion
This study revealed significantly lower all-cause mortality among participants in industry-sponsored RCTs compared with non-participants who received routine hospital outpatient care. This effect was independent of study drug.
Smart portable rehabilitation devices Mavroidis, Constantinos; Nikitczuk, Jason; Weinberg, Brian ...
Journal of neuroengineering and rehabilitation,
07/2005, Letnik:
2, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The majority of current portable orthotic devices and rehabilitative braces provide stability, apply precise pressure, or help maintain alignment of the joints with out the capability for real time ...monitoring of the patient's motions and forces and without the ability for real time adjustments of the applied forces and motions. Improved technology has allowed for advancements where these devices can be designed to apply a form of tension to resist motion of the joint. These devices induce quicker recovery and are more effective at restoring proper biomechanics and improving muscle function. However, their shortcoming is in their inability to be adjusted in real-time, which is the most ideal form of a device for rehabilitation. This introduces a second class of devices beyond passive orthotics. It is comprised of "active" or powered devices, and although more complicated in design, they are definitely the most versatile. An active or powered orthotic, usually employs some type of actuator(s).
In this paper we present several new advancements in the area of smart rehabilitation devices that have been developed by the Northeastern University Robotics and Mechatronics Laboratory. They are all compact, wearable and portable devices and boast re-programmable, real time computer controlled functions as the central theme behind their operation. The sensory information and computer control of the three described devices make for highly efficient and versatile systems that represent a whole new breed in wearable rehabilitation devices. Their applications range from active-assistive rehabilitation to resistance exercise and even have applications in gait training. The three devices described are: a transportable continuous passive motion elbow device, a wearable electro-rheological fluid based knee resistance device, and a wearable electrical stimulation and biofeedback knee device.
Laboratory tests of the devices demonstrated that they were able to meet their design objectives. The prototypes of portable rehabilitation devices presented here did demonstrate that these concepts are capable of the performance their commercially available but non-portable counterparts exhibit.
Smart, portable devices with the ability for real time monitoring and adjustment open a new era in rehabilitation where the recovery process could be dramatically improved.
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