New drugs for type 2 diabetes mellitus:what is their place in therapy?

Oral therapy for type 2 diabetes mellitus, when used appropriately, can safely assist patients to achieve glycaemic targets in the short to medium term. However, the progressive nature of type 2 diabetes usually requires a combination of two or more oral agents in the longer term, often as a prelude to insulin therapy. Issues of safety and tolerability, notably weight gain, often limit the optimal application of anti-diabetic drugs such as sulforylureas and thiazolidinediones. Moreover, the impact of different drugs, even within a single class, on the risk of long-term vascular complications has come under scrutiny. For example, recent publication of evidence suggesting potential detrimental effects of rosiglitazone on myocardial events generated a heated debate and led to a reduction in use of this drug. In contrast, current evidence supports the view that pioglitazone has vasculoprotective properties. Both drugs are contraindicated in patients who are at risk of heart failure. An additional recently identified safety concern is an increased risk of fractures, especially in postmenopausal women. Several new drugs with glucose-lowering efficacy that may offer certain advantages have recently become available. These include (i) injectable glucagonlike peptide-1 (GLP-1) receptor agonists and oral dipeptidyl peptidase-4 (DPP-4) inhibitors; (ii) the amylin analogue pramlintide; and (iii) selective cannabinoid receptor-1 (CB1) antagonists. GLP-1 receptor agonists, such as exenatide, stimulate nutrient-induced insulin secretion and reduce inappropriate glucagon secretion while delaying gastric emptying and reducing appetite. These agents offer a low risk of hypoglycaemia combined with sustained weight loss. The DPP-4 inhibitors sitagliptin and vildagliptin are generally weight neutral, with less marked gastrointestinal adverse effects than the GLP-1 receptor agonists. Potential benefits of GLP-1 receptor stimulation on P cell neogenesis are under investigation. Pancreatitis has been reported in exenatide-treated patients. Pramlintide, an injected peptide used in combination with insulin, can reduce insulin dose and bodyweight. The CB1 receptor antagonist rimonabant promotes weight loss and has favourable effects on aspects of the metabolic syndrome, including the hyperglycaemia of type 2 diabetes. However, in 2007 the US FDA declined approval of rimonabant, requiring more data on adverse effects, notably depression. The future of dual peroxisome proliferator-activated receptor-alpha/gamma agonists, or glitazars, is presently uncertain following concerns about their safety. In conclusion, several new classes of drugs have recently become available in some countries that offer new options for treating type 2 diabetes. Beneficial or neutral effects on bodyweight are an attractive feature of the new drugs. However, the higher cost of these agents, coupled with an absence of long-term safety and clinical outcome data, need to be taken into consideration by clinicians and healthcare organizations.

Restoring function after neuromuscular trauma: novel paradigms for enhancing volitional control of neural activity in untethered environments and vHAB, a gamified therapy platform

Thesis (Ph.D.)--University of Washington, 2016-08

Pelvic-Floor Rehabilitation, Part 1 : Comparison of Two Surface Electrode Placements During Stimulation of the Pelvic-Floor Musculature in Women Who Are Continent Using Bipolar Interferential Currents

Background and Purpose. Electrical stimulation of the pelvic floor is used as an adjunct in the conservative treatment of urinary incontinence. No consensus exists, however, regarding electrode placements for optimal stimulation of the pelvic-floor musculature. The purpose of this study was to compare two different bipolar electrode placements, one suggested by Laycock and Green (L2) the other by Dumoulin (D2), during electrical stimulation with interferential currents of the pelvic-floor musculature in continent women, using a two-group crossover design. Subjects. Ten continent female volunteers, ranging in age from 20 to 39 years (X̅=27.3, SD=5.6), were randomly assigned to one of two study groups. Methods. Each study group received neuromuscular electrical stimulation (NMES) of the pelvic-floor musculature using both electrode placements, the order of application being reversed for each group. Force of contraction was measured as pressure (in centimeters of water [cm H2O]) exerted on a vaginal pressure probe attached to a manometer. Data were analyzed using a two-way, mixed-model analysis of variance. Results. No difference in pressure was observed between the two electrode placements. Differences in current amplitude were observed, with the D2 electrode placement requiring less current amplitude to produce a maximum recorded pressure on the manometer. Subjective assessment by the subjects revealed a preference for the D2 electrode placement (7 of 10 subjects). Conclusion and Discussion. The lower current amplitudes required with the D2 placement to obtain recordings comparable to those obtained with the L2 technique suggest a more comfortable stimulation of the pelvic-floor muscles. The lower current amplitudes required also suggest that greater increases in pressure might be obtained with the D2 placement by increasing the current amplitude while remaining within the comfort threshold. These results will help to define treatment guidelines for a planned clinical study investigating the effects of NMES and exercise in the treatment of urinary stress incontinence in women postpartum.

Pelvic-Floor Rehabilitation, Part 1 : Comparison of Two Surface Electrode Placements During Stimulation of the Pelvic-Floor Musculature in Women Who Are Continent Using Bipolar Interferential Currents

Background and Purpose. Electrical stimulation of the pelvic floor is used as an adjunct in the conservative treatment of urinary incontinence. No consensus exists, however, regarding electrode placements for optimal stimulation of the pelvic-floor musculature. The purpose of this study was to compare two different bipolar electrode placements, one suggested by Laycock and Green (L2) the other by Dumoulin (D2), during electrical stimulation with interferential currents of the pelvic-floor musculature in continent women, using a two-group crossover design. Subjects. Ten continent female volunteers, ranging in age from 20 to 39 years (X̅=27.3, SD=5.6), were randomly assigned to one of two study groups. Methods. Each study group received neuromuscular electrical stimulation (NMES) of the pelvic-floor musculature using both electrode placements, the order of application being reversed for each group. Force of contraction was measured as pressure (in centimeters of water [cm H2O]) exerted on a vaginal pressure probe attached to a manometer. Data were analyzed using a two-way, mixed-model analysis of variance. Results. No difference in pressure was observed between the two electrode placements. Differences in current amplitude were observed, with the D2 electrode placement requiring less current amplitude to produce a maximum recorded pressure on the manometer. Subjective assessment by the subjects revealed a preference for the D2 electrode placement (7 of 10 subjects). Conclusion and Discussion. The lower current amplitudes required with the D2 placement to obtain recordings comparable to those obtained with the L2 technique suggest a more comfortable stimulation of the pelvic-floor muscles. The lower current amplitudes required also suggest that greater increases in pressure might be obtained with the D2 placement by increasing the current amplitude while remaining within the comfort threshold. These results will help to define treatment guidelines for a planned clinical study investigating the effects of NMES and exercise in the treatment of urinary stress incontinence in women postpartum.

A three species model to simulate application of hyperbaric oxygen therapy to chronic wounds

Chronic wounds are a significant socioeconomic problem for governments worldwide. Approximately 15% of people who suffer from diabetes will experience a lower-limb ulcer at some stage of their lives, and 24% of these wounds will ultimately result in amputation of the lower limb. Hyperbaric Oxygen Therapy (HBOT) has been shown to aid the healing of chronic wounds; however, the causal reasons for the improved healing remain unclear and hence current HBOT protocols remain empirical. Here we develop a three-species mathematical model of wound healing that is used to simulate the application of hyperbaric oxygen therapy in the treatment of wounds. Based on our modelling, we predict that intermittent HBOT will assist chronic wound healing while normobaric oxygen is ineffective in treating such wounds. Furthermore, treatment should continue until healing is complete, and HBOT will not stimulate healing under all circumstances, leading us to conclude that finding the right protocol for an individual patient is crucial if HBOT is to be effective. We provide constraints that depend on the model parameters for the range of HBOT protocols that will stimulate healing. More specifically, we predict that patients with a poor arterial supply of oxygen, high consumption of oxygen by the wound tissue, chronically hypoxic wounds, and/or a dysfunctional endothelial cell response to oxygen are at risk of nonresponsiveness to HBOT. The work of this paper can, in some way, highlight which patients are most likely to respond well to HBOT (for example, those with a good arterial supply), and thus has the potential to assist in improving both the success rate and hence the costeffectiveness of this therapy.

A review of non-traditional occupational therapy practice placement education : a focus on role-emerging and project placements

Practice placement education has been recognised as an integral and critical component of the training of occupational therapy students. Although there is an extensive body of literature on clinical education and traditional practice placement education models, there has been limited research on alternative placements.-------- This paper reviews the literature on various practice placement education models and presents a contemporary view on how it is currently delivered. The literature is examined with a particular focus on the increasing range of practice placement education opportunities, such as project and role-emerging placements. The drivers for non-traditional practice placement education include shortages of traditional placement options, health reform and changing work practices, potential for role development and influence on practice choice. The benefits and challenges of non-traditional practice placement education are discussed, including supervision issues, student evaluation, professional and personal development and the opportunity to practise clinical skills.--------- Further research is recommended to investigate occupational therapy graduates' perceptions of role-emerging and project placements in order to identify the benefits or otherwise of these placements and to contribute to the limited body of knowledge of emerging education opportunities.

Prevalence and correlates of low back pain among occupational therapy students in Northern Queensland

Background: Although low back pain (LBP) is an important issue for the health profession, few studies have examined LBP among occupational therapy students. Purpose. To investigate the prevalence and distribution of LBP, its adverse sequelae; and to identify potential risk factors.----------- Methods: In 2005, a self-reported questionnaire was administered to occupational therapy students in Northern Queensland.----------- Findings: The 12-month period-prevalence of LBP was 64.6%. Nearly half (46.9%) had experienced pain for over 2 days, 38.8% suffered LBP that affected their daily lives, and 24.5% had sought medical treatment. The prevalence of LBP ranged from 45.5 to 77.1% (p=0.004), while the prevalence of LBP symptoms persisting longer than two days was 34.1 to 62.5% (p=0.020). Logistic regression analysis indicated that year of study and weekly computer usage were statistically-significant LBP risk factors.----------- Implications: The occupational therapy profession will need to further investigate the high prevalence of student LBP identified in this study.

Upper body musculoskeletal disorders among Australian occupational therapy students

Although upper body musculoskeletal disorders (MSDs) represent an increasingly important issue for university students, few if any studies have targeted the occupational therapy faculty. Given this dearth of information, it was considered necessary to investigate a cross-section of Australian occupational therapy students by means of an established questionnaire survey. Completed replies were obtained from 95.7%, 100% and 97.7% (n = 44, 55 and 48) of students in the first, second and fourth years of a large occupational therapy school in northern Queensland, Australia.---------- The 12-month period prevalence of MSDs was as follows: neck (67.4%), shoulder (46.3%) and upper back (39.5%). Three-quarters of all students (75.5%) reported an MSD occurring in at least one of these body regions. Over half (56.5%) reported an MSD over 2 days' duration in the past year. Almost 40% (39.5%) reported an MSD that had affected their daily life, while one-quarter (25.2%) needed some type of treatment.---------- Logistic regression indicated that students aged over 21 years were almost four times more likely to report shoulder-related MSD (OR 3.7, 95%CI: 1.4-10.2). Year of study in the occupational therapy course was another important MSD correlate, with adjusted odds ratios ranging from 3.3 at the upper back (OR 3.3, 95%CI: 1.2-9.6) to 10.9 at the neck (OR 10.9, 95%CI: 3.2-43.8). Computer usage also incurred a certain degree of risk, with students who spent over 5 hours per week on the computer having an increased risk of MSD at the neck (OR 5.0, 95%CI: 1.3-21.5) and shoulder (OR 4.7, 95%CI: 1.4-18.3).---------- Overall, this study suggests that Australian occupational therapy students have a large burden from MSDs in the upper body region, even more so than other student groups and some working populations. Since the distribution of MSD risk is not uniform among them, interventions to help reduce these conditions need to be carefully targeted. Further longitudinal investigations would also be useful in determining the mechanisms and contributory factors for MSDs among this unique student population.