Ease Of Delivery Research Articles

Repeated botulinum toxin injection for idiopathic overactive bladder: Will chemodenervation become a long-term solution?

Botulinum toxin A (BTX-A) has emerged as a novel treatment option for idiopathic overactive bladder (OAB) refractory to antimuscarinic agents. The clinical needs of refractory OAB patients have been recently met by sacral neuromodulation and augmentation enterocystoplasty. Important features of BTX-A should include safety, efficacy, and ease of delivery during long-term repeated usage. This article reviews the role of repeated BTX-A injections in the treatment of idiopathic OAB.

Immediate and midterm follow-up results of using an electrodetachable, fully retrievable SOLO stent system in the endovascular coil occlusion of wide-necked cerebral aneurysms

Stent-assisted embolization is an alternative endovascular treatment method for wide-necked intracranial aneurysms. Currently available stents have the limitations of poor radial force, difficult delivery systems, and lack of full retrievability. The authors report on their preliminary experience with the use of a new, fully retrievable, self-expanding neurovascular stent, which has a high radial force and easy delivery system, combined with coil or Onyx embolization for the treatment of wide-necked aneurysms, including 6-month follow-up data. Fifteen patients with 18 wide-necked intracranial aneurysms were treated using the SOLO stent system and detachable platinum coils. Aneurysms were located at the posterior communicating artery (seven lesions), midbasilar artery (one lesion), internal carotid artery (ICA) bifurcation (one lesion), ICA-ophthalmic artery segment (eight lesions), and posterior cerebral artery (one lesion). Eleven aneurysms were small, six were large, and one was giant. Only one of these aneurysms was in the acute stage of subarachnoid hemorrhage; balloon remodeling alone failed to keep the coils in the aneurysm sac. Only one stent required retrieving and repositioning after it had been fully deployed, and retrieval was easy and successful. No thromboembolic complication, dissection/rupture, or vasospasm occured during stent placement. Follow-up angiograms obtained at 6 months posttreatment in the 18 aneurysms demonstrated that all stents were patent with no evidence of intimal hyperplasia or stenosis. In all cases but one, 100% lesion occlusion was observed at the 6-month control angiography examination. Only one aneurysm had recanalized. The fully retrievable self-expandible SOLO stent is a feasible, secure, and effective system with a high radial force and ease of delivery in treating wide-necked intracranial aneurysms in combination with coil embolization.

Infections, Immunity & their Effects on Asthma

Infections, Immunity & their Effects on Asthma

Particulate delivery systems for animal vaccines

The requirements for veterinary vaccines are different to those of human vaccines. Indeed, while more side effects can be tolerated in animals than in humans; there are stricter requirements in terms of cost, ease of delivery (including to wildlife), and a need to develop vaccines in species for which relatively little is known in terms of molecular immunology. By their nature particulate vaccine delivery systems are well suited to address these challenges. Here, we review particulate vaccine delivery systems, ranging from cm-sized long-distance ballistic devices to nano-bead technology for veterinary species and wildlife.

Plant-made subunit vaccine against pneumonic and bubonic plague is orally immunogenic in mice

Yersinia pestis, the causative agent of plague, is an extremely virulent bacterium but there are no approved vaccines for protection against it. Our goal was to produce a vaccine that would address: ease of delivery, mucosal efficacy, safety, rapid scalability, and cost. We developed a novel production and delivery system for a plague vaccine of a Y. pestis F1–V antigen fusion protein expressed in tomato. Immunogenicity of the F1–V transgenic tomatoes was confirmed in mice that were primed subcutaneously with bacterially-produced F1–V and boosted orally with transgenic tomato fruit. Expression of the plague antigens in fruit allowed producing an oral vaccine candidate without protein purification and with minimal processing technology.

AZA Wildlife Contraception Center Programs

Author(s): Asa, Cheryl S. | Abstract: Controlling reproduction is a responsibility facing both zoo and wildlife managers, and contraception is one of their options. However, management goals and parameters affecting administration of contraceptives vary considerably for free-ranging and captive wildlife. Captive breeding programs consider the entire captive population but manage at the level of the individual. Not only must they focus on the genetic value of individual animals, but each birth results in an animal that will require resources and occupy limited space for its lifetime. Thus, captive programs dictate that contraceptive be virtually 100% effective, safe, and reversible. This contrasts with management of most free-ranging animals, where reproductive rate of the population, not each individual, is the measure of success. The other notable distinction is ease of delivery in captive populations, perhaps the greatest challenge with free-ranging animals. Captive animals are always accessible, are individually known, and can be monitored. Yet, despite these differences, zoo and wildlife biologists can benefit from collaborative efforts, especially when they target the same species. In particular, trials with captive animals can provide more definitive results than comparable studies with free-ranging animals. In addition, we all face the problems inherent in programs that represent a limited commercial market. Improved communication and exploring the potential for collaborations may accelerate our progress.

1028. Use of Antisense Oligonucleotides To Restore Activity in Mutant p53

Top of pageAbstract The tumor suppressor p53 protects the cell against cancer by inducing cell cycle arrest and apoptosis in response to oncogenic stress. Over 50% of human malignancies are associated with missense mutations within the protein's central sequence-specific DNA- binding domain. The C-terminus of p53 contains a regulatory domain that binds to specific structural features of damaged DNA (ends, distortions, modifications caused by gamma irradiation). Deletion or inactivation of the C-terminal regulatory domain (CTRD), using peptides or monoclonal antibodies in culture, has been shown to compensate for missense mutations in the sequence-specific DNA- binding domain. Unfortunately, peptides and monoclonal antibodies are difficult to deliver to cells and are immunogenic when used in vivo. Several RNA antisense oligonucleotides (ASOs), modified for increased stability, have been designed to alter the splicing of the p53 pre-mRNA to delete the CTRD. TOV-112D is a human endometrioid carcinoma cell line, which harbors a mutant p53 (Arg175His). We are testing a variety of ASOs in TOV-112D cells to assay for transcriptionally active mutant p53s. Apoptosis and p53 reporter assays will also be used to indicate restored p53 functional activity. The results of these experiments will be presented at the meeting. ASOs are more amenable to therapeutic application in comparison to antibodies and peptides given increased stability of modified RNA, decreased immunogenicity, and relative ease of delivery.

Improving psychologic adjustment to chronic illness in cardiac patients

Poor mood adjustment to chronic medical illness is often accompanied by decrements in function. To evaluate the effectiveness of a telephone-based intervention for psychologic distress and functional impairment in cardiac illness. Randomized, controlled trial. We recruited survivors of acute coronary syndromes using the Hospital and Anxiety Depression Scale (HADS) with scores indicative of mood disturbances at 1-month postdischarge. Recruited patients were randomized to experimental or control status. Intervention patients received 6 30-minute telephone counseling sessions to identify and address illness-related fears and concerns. Control patients received usual care. Patients' responses to the HADS and the Workplace Social Adjustment Scale (WSAS) were collected at baseline, 2, 3, and 6 months using interactive voice recognition technology. At baseline, the PRIME-MD was used to establish diagnosis of depression. We used mixed effects regression to study changes in outcomes. We enrolled 100 patients. Mean age was 60; 67% of the patients were male. Findings confirmed that the intervention group had a 27% improvement in depression symptoms (P=.05), 27% in anxiety (P=.02), and a 38% improvement in home limitations (P=.04) compared with controls. Symptom improvement tracked those for WSAS measures of home function (P=.04) but not workplace function. The intervention had a moderate effect on patient's emotional and functional outcomes that were observed during a critical period in patients' lives. Patient convenience, ease of delivery, and the effectiveness of the intervention suggest that the counseling can help patients adjust to chronic illness.

Treatment of digital myxoid cysts with infrared coagulation: a retrospective case series

Digital myxoid cysts (DMC) are often unsightly; they may cause nail dystrophy and are sometimes painful. There is a multitude of existing therapies and recurrences are not uncommon; some treatments may be painful or result in scarring. Infrared coagulation (IRC) produces predictable thermal injury with relative sparing of superficial tissues and represents an alternative treatment modality in DMC. To assess the outcome of treatment of DMC with IRC. Twenty-two patients with DMC treated with IRC were identified retrospectively (23 DMC: 18 finger and five toe). IRC was delivered to the area of the cyst under local anaesthesia. Of the 23 lesions treated with IRC 86% responded; these included 73% that resolved after a single treatment, one lesion that relapsed after 3 years, one lesion that was reduced in size and one lesion that required three treatments over 18 months but has not recurred over the subsequent 9 years. There were three early recurrences that required treatment with other modalities: two were successfully treated with surgery and one responded to a single treatment with cryotherapy. One patient was excluded from the analysis because it was not possible to assess her adequately. We present long-term follow-up data (mean follow-up 4.8 years, range 10 months-10.5 years) of the treatment of DMC with IRC. Treatment was well tolerated, with few side-effects, and cosmetic outcome was excellent. While recurrence rates were similar to many existing therapies, the ease of delivery, tolerability and cosmetic results make IRC a favourable option for the treatment of DMC.

Stents and sensibility?use of the Montgomery T-tube in tracheal stenosis

Pereszlenyi and colleagues [1] exhaustive account of their institution’s experience with management of tracheal stenosis brings forth several important points. The first and most important issue is the choice of stent—metallic expandable or silicon stents. The ease of delivery of metallic stents through flexible bronchoscopy under topical anesthesia has unfortunately resulted in their overuse [2]. Expandable stents induce intense granulation tissue and are difficult, sometimes impossible, to remove. They frequently convert resectable lesions to lesions of irresectable length [3]. Surgery is much more demanding after prior intervention with metallic stents owing to the severe tissue reaction that they produce. Single and short segment tracheal stenosis should be treated by primary surgery in centres experienced in tracheal surgery. Stenting should be reserved for patients with terminal malignancy (where self-expandable stents may be preferred) and in an acute situation (where silicone stents may be deployed as a temporary measure) prior to referral to a centre specializing in tracheal surgery. Dumon stents and Montgomery T-tubes are invaluable in stenting lesions, which are too long for safe reconstruction [3]. We agree with the authors that though granulation tissue still may form with a silicon stent, this is considerably less compared to that caused by an expandable metallic stent. Moreover, the ease with which silicon stents can be removed if definitive surgery is being considered makes it an attractive option to tide over an acute situation. Long segment and multiple segment stenosis not suitable for surgical resection may also be managed with silicon stents. More often than not (as seen in Pereszlenyi’s series), the stent stabilizes the airway and decannulation is possible in most cases. We wonder what the authors’ criteria are to consider removal of the T-tube as some of their patients have been managed only with a T-tube for relatively prolonged periods (118 months). Generally, decannulation is possible in about 6–12 months. The pulmonologist or thoracic surgeon involved in managing complex airway problems needs to be aware of the basic pathology underlying tracheobronchial stenosis and intelligently apply the right solution to a specific problem.

Prosthetic Design Considerations for Anterior Single‐Implant Restorations

The anterior single-implant restoration provides a predictable solution for the partially edentulous patient. The two main approaches in prosthesis design for the single-implant restoration are the screw-retained and cement-retained restorations. Although both approaches have been proven to work from a standpoint of long-term implant stability, other considerations arise when esthetic outcome and ease of fabrication and delivery are discussed. To guarantee a predictable outcome, the dentist should choose a design that offers maximum prosthetic versatility. Combining prosthetic versatility with ease of delivery is often a clinical and laboratory challenge. Prostheses designs that provide the freedom to select a wide variety of restorative materials may be cumbersome to deliver and maintain and vice versa. This article reviews the advantages and shortcomings of each design and provides an alternative prosthesis design that combines the favorable aspects of these two restorations. Screw-retained and cement-retained prostheses are the common designs for single-implant restorations and possess clinical advantages and shortcomings. An alternative and affordable design, that is mainly beneficial when standard stock implants components are used, is presented. It enables the clinician to achieve optimal esthetics in the esthetic zone combined with a simple and time-efficient delivery.

Fatal Pulmonary Complications after Arterial Embolization with 40–120-μm Tris-acryl Gelatin Microspheres

Hepatic arterial embolization is a recognized method of treating primary malignancies and some secondary hepatic malignancies. Particle embolization alone has been shown to be safe and effective and is routinely performed for hypervascular tumors. Tris-acryl gelatin microspheres have been widely acclaimed for their ease of delivery and uniform size, allowing for accurate targeting of particular end arteries. There have been three deaths at the author's institution related to respiratory compromise since the 40-120- micro m particles became available 31 months ago. These complications were never observed with larger tris-acryl gelatin microspheres or polyvinyl alcohol particles. This is an unusual and serious complication of which interventionalists performing embolotherapy need to be aware.

Technological challenges in counter bioterrorism.

This article focuses on bioterrorism, which plays a major role in the CBRNE arsenal because of their relative ease of delivery brought about by low visibility, high potency, and substantial accessibility.

In vivo evaluation of a new bioabsorbable self-expanding biliary stent

Background Bioabsorbable stents may offer advantages for the treatment of benign and malignant biliary strictures, including large stent diameter, decreased biofilm accumulation and proliferative changes, elimination of the need for stent removal and imaging artifacts, and prospects for drug impregnation. However, suboptimal expansion has hampered prior iterations. A new bioabsorbable biliary stent (BioStent) was evaluated in a porcine model. Methods BioStents were placed in 8 animals for long-term follow-up. The following were evaluated: accuracy and ease of delivery and deployment, radial expansion, and radiologic visualization. Stent function and biotolerance were assessed by cholangiography, serum bilirubin, and necropsy for histopathology performed in pairs at 2, 4, 6, and 12 months. Results Stents were delivered without sphincterotomy and were deployed easily, accurately, and with good immediate stent expansion and radiographic visualization. On follow-up, all stents were fully expanded and serum bilirubin levels remained within the normal range. Although there was no clinical evidence of biliary obstruction, filling defects were common at cholangiography. On histopathologic evaluation, there was neither bile duct integration or proliferative change. Conclusions The BioStent bioabsorbable biliary stent, modified with axial runners, can be effectively deployed endoscopically, is self-expanding, is visualized radiographically, and remains patent up to 6 months. There was no bile duct integration or proliferative change, which are potential advantages. Stent occlusion and migration remain concerns.

Differential effects of aging on transport properties of anterior and posterior human sclera

The transport properties and composition of 44 pairs of human sclera, 37–91 years were compared. Solute transport, diffusion and partition coefficients of posterior sclera for solutes ranging in mass from 0·023–70 kDa were higher than those of anterior sclera; the posterior region was also more hydrated. The differences in partition coefficient between anterior and posterior sclera became more pronounced as solute molecular weight increased. Partition coefficients and hydration of both regions decreased with increasing age. Chondroitinase ABC digestion, which removed the majority of glycosaminoglycans, increased partition coefficients of both regions significantly. These results suggest that for regions of equal scleral thickness, neglecting the influence of vascular factors, drug delivery will be more readily achieved across the posterior sclera than the anterior sclera in the age group studied and that, for both regions, ease of delivery will decrease with decreasing age.

Superiority and equivalence in thrombolytic drugs: an interpretation.

Streptokinase and alteplase both reduce mortality from acute myocardial infarction. Newer thrombolytic drugs (reteplase and tenecteplase) have putative advantages, such as ease of delivery and better fibrin specificity, although they are more expensive. A systematic review and meta‐analysis identified the clinical efficacy and adverse effects of these drugs.1 But this can only compare drugs where there are direct trial comparisons. Inevitably, we need to make indirect comparisons also, as well as to interpret the results of the direct comparisons. We present an interpretation and consider its strengths and weaknesses. Broadly, ‘superiority studies’, where one drug is thought likely to be better than another, assume a null hypothesis that there is no difference, which may then be disproved. Such studies are usually analysed by intention to treat (ITT, i.e. to analyse all patients according to their initial randomized allocation, and not whether they ever received the therapy or changed at some point to the alternative therapy). The null hypothesis and ITT are conservative, and limit the chances of a type 1 error, i.e. ascribing a difference where none exists.2 Equivalence trials examine whether a new therapy is as effective as an existing standard. Equivalence studies might also be used to compare adverse effects, or costs of two effective drugs. In a randomized trial, the two drugs are unlikely to produce exactly the same results (this would be the case even if we compared one drug to itself). We must therefore define ‘equivalence’ a priori , i.e. what is the range of apparent difference in efficacy between two therapies, within which the therapies may be considered clinically equivalent. This is an arbitrary decision. For thrombolytics, the efficacy is usually recorded as 30‐ or 35‐day mortality. The American College of Chest Physicians (ACCP)3 and others4 have suggested that the …

Optimising postoperative pain management in the ambulatory patient.

Over 60% of surgery is now performed in an ambulatory setting. Despite improved analgesics and sophisticated drug delivery systems, surveys indicate that over 80% of patients experience moderate to severe pain postoperatively. Inadequate postoperative pain relief can prolong recovery, precipitate or increase the duration of hospital stay, increase healthcare costs, and reduce patient satisfaction. Effective postoperative pain management involves a multimodal approach and the use of various drugs with different mechanisms of action. Local anaesthetics are widely administered in the ambulatory setting using techniques such as local injection, field block, regional nerve block or neuraxial block. Continuous wound infusion pumps may have great potential in an ambulatory setting. Regional anaesthesia (involving anaesthetising regional areas of the body, including single extremities, multiple extremities, the torso, and the face or jaw) allows surgery to be performed in a specific location, usually an extremity, without the use of general anaesthesia, and potentially with little or no sedation. Opioids remain an important component of any analgesic regimen in treating moderate to severe acute postoperative pain. However, the incorporation of non-opioids, local anaesthetics and regional techniques will enhance current postoperative analgesic regimens. The development of new modalities of treatment, such as patient controlled analgesia, and newer drugs, such as cyclo-oxygenase-2 inhibitors, provide additional choices for the practitioner. While there are different routes of administration for analgesics (e.g. oral, parenteral, intramuscular, transmucosal, transdermal and sublingual), oral delivery of medications has remained the mainstay for postoperative pain control. The oral route is effective, the simplest to use and typically the least expensive. The intravenous route has the advantages of a rapid onset of action and easier titratibility, and so is recommended for the treatment of acute pain.Non-pharmacological methods for the management of postoperative pain include acupuncture, electromagnetic millimetre waves, hypnosis and the use of music during surgery. However, further research of these techniques is warranted to elucidate their effectiveness in this indication. Pain is a multifactorial experience, not just a sensation. Emotion, perception and past experience all affect an individual's response to noxious stimuli. Improved postoperative pain control through innovation and creativity may improve compliance, ease of delivery, reduce length of hospital stay and improve patient satisfaction. Patient education, early diagnosis of symptoms and aggressive treatment of pain using an integrative approach, combining pharmacotherapy as well as complementary technique, should serve us well in dealing with this complex problem.

Safety of Chewable Tablets for Children

New emphasis on pediatric drug development makes the availability of safe, easy-to-use dosage formulations imperative for clinical practice. Chewable tablets are a widely used pediatric dosage form; however, a literature review on the safety of this formulation has not been published. We have, therefore, determined the safety of chewable tablets in the pediatric age group based on the published literature. A search of safety information on chewable tablets was performed from the published literature dating from January 1966 to January 1999. Search terms included tablet, chewable tablet, drug formulation, aspiration, choking, asphyxia, airway obstruction, and foreign body. Additional information was obtained from the Physician's Desk Reference, by purchasing products at a local drug store, from calls to manufacturers, and from the IMS Health National Prescription Audit Plus 7. Human, English-language studies of two types were included: clinical articles with any mention of chewable tablets, and aspiration case series. The results of this review showed that more than 60 chewable tablet formulations are approved for use in the United States. Medical issues, including foreign-body injuries, related to the chewable-tablet formulation were extremely rare. The advantages of chewable tablets include palatability, stability, precise dosing, portability, and ease of delivery. It is concluded that the available literature suggests that chewable tablets provide a safe, well-tolerated alternative to traditional pediatric drug formulations and offer significant advantages in children 2 years of age and older.

The Amplatzer duct occluder: experience in 209 patients

OBJECTIVESThe aim of the study was to assess the safety and efficacy of the Amplatzer ductal occluder (ADO) in transcatheter occlusion of patent ductus arteriosus (PDA).BACKGROUNDTranscatheter closure of small to moderate sized PDAs is an established procedure. The ADO is a self-expandable device with a number of salutary features, notably its retrievability, ease of delivery via small 5F to 7F catheters and a range of sizes suitable even for the larger PDAs.METHODSBetween November 1997 and August 1999, the ADO was successfully implanted in 205 of 209 patients with PDA. The inclusion criteria for this device occlusion method were patients with clinical and echocardiographic features of moderate to large PDA, weighing ≥3.5 kg as well as asymptomatic adolescents and adults with PDA measuring ≥5.0 mm on two-dimensional (2D) echocardiogram. Occlusion was achieved via the antegrade venous approach. Follow-up evaluations were performed with 2D echocardiogram, color-flow mapping and Doppler measurement of the descending aorta and left pulmonary artery velocity at 24 h and 1, 3, 6 and 12 months after implantation.RESULTSTwo hundred and five patients had successful PDA occlusion using this device. The patients were between two months and 50 years (median 1.9) and weighed between 3.4 kg and 63.2 (median 8.4). Infants made up 26% of the total patients. The PDA measured from 1.8 to 12.5 mm (mean 4.9) at the narrowest diameter. Forty-four percent of patients achieved immediate complete occlusion. On color Doppler the closure rates at 24 h and 1 month after implant were 66% and 97%, respectively. At 6 and 12 months all except one patient attained complete occlusion. Device embolization occurred in three patients; in two this was spontaneous, and in the other it was due to catheter manipulation during postimplant hemodynamic measurement. Mild aortic narrowing was seen in an infant.CONCLUSIONSPatent ductus arteriosus occlusion using ADO is safe and efficacious. It is particularly useful in symptomatic infants and small children with relatively large PDA. Embolization can be minimized by selection of appropriate sized devices, and caution should be exercised in infants <5 kg.

Inhaled Drug Therapy During Mechanical Ventilation

In mechanically ventilated patients, drug delivery by inhalation is a common route of administration for an increasing number of pharmacologic agents. Inhalation of a therapeutic aerosol has advantages compared with other routes of drug administration with respect to convenience, ease of delivery, and safety. As with any drug, administration of an inhaled agent to a targeted site in an appropriate amount is essential for a therapeutic effect. Drug delivery is influenced by the physicochemical properties of the aerosolized drug, characteristics of the aerosol-generating device, technique of aerosol delivery, mechanical ventilator parameters, and airway anatomy. Lower respiratory tract deposition is diminished in ventilator-dependent patients due to losses arising from aerosol impaction on the ventilator circuit and endotracheal tube. For optimal drug delivery, the clinician should be familiar with the aerosol-generating device and technique of delivery, including mechanical ventilator parameters. Therapeutic gases such as nitric oxide and helium have been used as pharmacologic adjuncts during mechanical ventilation. Lower respiratory tract delivery of a therapeutic gas is influenced simply by gas diffusion. However, delivery of such agents to the mechanically ventilated patient is complicated by the requirement for specialized gas blenders and monitoring equipment. Inhaled drug delivery has the potential to modify the underlying respiratory pathophysiology while producing few systemic effects. In the future, the number of agents that can be administered by the inhalation route to mechanically ventilated patients will continue to expand. Clin Pulm Med 2000;7(3):140-146