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My First Six Months (MF6M) is a learning and teaching initiative that was implemented in three first year studio courses in an undergraduate Industrial Design degree in an Australian metropolitan university.

In this study, assessment and learning is reconceptualised as an integrated and dialogic process. Positioned in a sociocultural framework, the experiences of academics and students at an Australian...

Obstructive sleep apnoea is highly prevalent in acute coronary syndrome patients eligible for enrolment in cardiac rehabilitation programmes. This condition is an independent predictor of increased morbidity and comorbid conditions in the general population and can lead to an increase in major adverse cardiac events such as revascularization, heart failure and hospital readmission in cardiac patients. There is convincing evidence that treatments such as continuous positive airway pressure or mandibular advancement devices can successfully treat obstructive sleep apnoea and these conditions can be improved or negated resulting in improved cardiac rehabilitation outcomes and improved health related quality of life. Given the potential benefits of obstructive sleep apnoea treatment it would make sense to screen for this condition upon entry to out-patient cardiac rehabilitation programmes. A two-stage approach to screening is recommended, where patients are initially evaluated for the probability of having obstructive sleep apnoea using a brief questionnaire (The STOP-Bang) and then followed up with objective evaluation (portable home monitor or polysomnography) where necessary. Potential barriers to further referral and treatment could be partly mitigated by the training of cardiac rehabilitation staff in sleep disorders and screening.

Design plays a marginal part in the discourse of diabetes care, mainly in visualizing the form and packaging of medical technologies. The authors however have a practice that advocates that design orientated solutions can add much needed dimensions to problems that have traditionally been the exclusive preserve of expert discourses. This position has for long been a validated and largely accepted approach in design’s engagement with issues in sustainability and development studies. A similar approach in the area of medicine has been constructed by the authors and marks out a position of advocacy where the designer takes on agency to intervene on behalf of the user community. This position contains a healthy critique of the traditional approach of product design for manufacture while simultaneously amplifying a desire to intervene and make a substantial improvement in the quality of life of people with diabetes. This article first opens out contemporary diabetes care as a contested domain and then goes on to sketch out the key aspects of a design practice focussed upon delivering positive health outcomes in diabetes care. The specific context of discussion for this article is the practice of teaching in design studios where students of design listen to the voices of people with diabetes and visualize ways for design to provide products and service solutions that transform the lived experiences of people with diabetes.

This study was part of a Phase 3 program treating crow's feet lines (CFL) with onabotulinumtoxinA.To evaluate the efficacy and safety of onabotulinumtoxinA treatment of CFL.This multicenter, double-blind, placebo-controlled, 5-month study randomized subjects with moderate-to-severe CFL (maximum smile) to onabotulinumtoxinA (24 U; n = 222) or placebo (n = 223). Investigators and subjects assessed CFL severity (maximum smile and rest) using the 4-grade Facial Wrinkle Scale (FWS). Co-primary end points were investigator- and subject-assessed proportion of subjects achieving a CFL FWS grade of 0 (none) or 1 (mild) at maximum smile (Day 30). Additional efficacy end points, patient-reported outcomes, and safety/adverse events (AEs) were evaluated.All primary and secondary end points were achieved; statistically significant differences favored onabotulinumtoxinA (p.001, all comparisons vs placebo). Co-primary responder rates were 66.7% compared with 6.7% for investigator-assessed and 58.1% compared with 5.4% for subject-assessed response (onabotulinumtoxinA group and placebo, respectively; p.001). A significantly greater proportion of the onabotulinumtoxinA group than placebo group achieved a 1 grade or greater improvement on the FWS (maximum smile and rest assessed by both the investigator and subject; all time points; p.001). Most AEs were mild or moderate and did not result in discontinuations.Treatment of moderate-to-severe CFL with onabotulinumtoxinA was effective and well tolerated.

Background:Uncontrolled complement activation plays a pivotal role in a variety of disorders such as paroxysmal nocturnal hemoglobinuria (PNH). Challenges to be addressed with eculizumab therapy include inter-individual variation in clearance of eculizumab, economic burden, and improvements in the current biweekly intravenous infusion maintenance schedule. ALN-CC5 is a subcutaneous (SC) investigational RNA interference (RNAi) therapeutic targeting hepatic complement C5 (C5) synthesis. Previously presented data from our ongoing Phase 1/2 study showed that ALN-CC5 was generally well tolerated and exhibited a clamped C5 knockdown and complement activity inhibition in healthy volunteers (Hill et al. Haematologica 2016; 101, Suppl 1). The aim of this abstract is to report updated tolerability and clinical activity of ALN-CC5 in patients with PNH. Methods: A phase 1/2 single-ascending dose (Part A) and multiple-ascending dose study (Part B) of ALN-CC5 was conducted in healthy adult volunteers and in patients with PNH (Part C). In Part C, patients with PNH received weekly doses of 200 mg or 400 mg of ALN-CC5 for 2 to 16 weeks; ALN-CC5 is administered subcutaneously at a concentration of 200 mg/mL. The primary endpoints are safety and tolerability and secondary endpoints include: pharmacokinetics (PK), reduction of circulating C5 and complement activity, as measured by CAP/CCP Wieslab ELISA assays and sheep erythrocyte hemolysis assay, as well as reduction in LDH. Results: Part C included 6 patients with PNH (treatment naïve n=3; patients receiving eculizumab n=3), including 1 patient who was experiencing breakthrough hemolysis despite receiving 1200mg eculizumab q2wk. ALN-CC5 was generally well tolerated in patients with PNH after multiple doses with the majority of adverse events (AEs) being mild or moderate in severity. There were no serious AEs or discontinuations due to AEs. One patient, who was also taking eculizumab, cyclosporine and anabolic steroids as concomitant medications, experienced a transient asymptomatic grade 3 elevation of liver transaminases that was deemed possibly related to study drug. In eculizumab naïve patients (n=3), ALN-CC5 monotherapy achieved a mean maximum C5 knockdown of 98.2% ± 0.3%, residual C5 levels of 0.9 mcg/mL and a mean maximum CCP inhibition of 94.2 ± 1.7%. During treatment with ALN-CC5, maximum reduction in LDH was 37% and 50% in 2 patients who received 17 doses of ALN-CC5 but remained above the goal of less than 1.5 times the ULN. In the remaining eculizumab naïve patient, LDH lowering was not observed following 8 doses of ALN-CC5. After completion of ALN-CC5 dosing and in the setting of ongoing >95% ALN-CC5-mediated KD of serum C5, treatment naïve patients received a single 600 mg dose of eculizumab (labeled induction dose is 600 mg weekly x 4) for the treatment of residual hemolysis followed by close clinical monitoring. An exploratory analysis was conducted to understand the potential for ALN-CC5 to reduce eculizumab dose and frequency. All 3 patients achieved sustained lowering of LDH Conclusion: ALN-CC5 was shown to be generally well tolerated in patients with PNH. The PD effects of ALN-CC5 were found to be durable, with clamped C5 knockdown and complement activity inhibition. Collectively, the data suggest that clamped inhibition of hepatic C5 synthesis may provide the foundation to potentially reduce the dose and frequency of eculizumab administration for patients with PNH, and to improve disease control in patients with inadequate response to eculizumab. Disclosures Hill: Alnylam Pharmaceuticals: Consultancy, Honoraria. Griffin:Alexion Pharmaceuticals: Honoraria, Other: Conference support. Munir:Alexion pharmaceuticals: Honoraria. Borodovsky:Alnylam Pharmaceuticals: Employment, Equity Ownership. Kawahata:Alnylam Pharmaceuticals: Employment, Equity Ownership. Mclean:Alnylam Pharmaceuticals: Employment, Equity Ownership. Shi:Alnylam Pharmaceuticals: Employment, Equity Ownership. Partisano:Alnylam: Employment, Equity Ownership. Kim:Alnylam Pharmaceuticals: Employment, Equity Ownership. Najafian:Alnylam Pharmaceuticals: Employment, Equity Ownership.

Introduction: Uncontrolled complement activation plays a pivotal role in a variety of disorders such as PNH and aHUS. ALN-CC5 is a subcutaneous (SC) investigational RNAi therapeutic targeting complement C5 (C5). In preclinical studies, ALN-CC5 has demonstrated decreased terminal complement activity. Based on the literature, preventing the generation of the terminal complex protects against intravascular hemolysis and complement-mediated tissue damage. The purpose of this study is to evaluate the safety and tolerability of ALN-CC5 in normal healthy volunteers. Material and methods: A multi-centered, placebo controlled, double blind phase 1 clinical study in healthy volunteers is ongoing. Several cohorts of healthy volunteers in Part A, a single ascending dose study and Part B, a weekly multiple ascending dose study have been completed. Primary endpoints are safety and tolerability. Secondary endpoints are pharmacokinetics, reduction of circulating C5, reduction in hemolytic, CAP and CCP activity. Results: In Part A, 20 healthy volunteers were randomized (1:3) to placebo or single SC dose of 50, 200, 400, 600 or 900mg of ALN-CC5 and followed for at least 70 days. In Part B, 12 healthy volunteers were randomized (1:3) to placebo or 5 weekly doses of 100, 200 or 400mg of ALN-CC5. No SAEs or study discontinuations occurred and overall ALN-CC5 was considered safe and generally well tolerated. A dose dependent and 94% mean maximum C5 knockdown was achieved following weekly administration. Updated safety and tolerability data as well as C5 knockdown, and changes in CAP, CCP and hemolytic activity from the study will be presented. Conclusion: Collectively, these initial results suggest that the use of a novel RNAi therapeutic targeting C5 is a promising approach for inhibiting complement in PNH, aHUS and other complement-mediated diseases. The subcutaneous route of administration and infrequent dosing make this a potentially encouraging therapy. Disclosures Hill: Alnylam: Consultancy. Off Label Use: ALN-CC5 is an investigational RNAi therapeutic targeting complement C5.. Borodovsky:Alnylam Pharmaceuticals: Employment, Equity Ownership. Kawahata:Alnylam Pharmaceuticals: Employment, Equity Ownership. Mclean:Alnylam Pharmaceuticals: Employment, Equity Ownership. Powell:Alnylam Pharmaceuticals: Employment, Equity Ownership. Chaturvedi:Alnylam Pharmaceuticals: Employment, Equity Ownership. Warner:Alnylam Pharmaceuticals: Employment, Equity Ownership. Garg:Alnylam Pharmaceuticals: Employment, Equity Ownership. Sorensen:Alnylam Pharmaceuticals: Employment, Equity Ownership.

Two groups of six men took levo-norgestrel (250 or 500 microgram daily) by mouth and testosterone oenanthate (200 mg monthly, intramuscurlarly) for six months. A three months placebo period preceded the medication which was followed by a recovery phase of 6-10 months. Two volunteers withdrew due to side effects. The five men taking the low doses of levo-norgestrel (250 microgram) exhibited a reduction in sperm count, but not to azoospermia. The high dose of levo-norgestrel (500 microgram) was more effective, sperm count was reduced to6 X 10(6)/ml in 3 of 5 volunteers and to17 X 10(6)/ml in the remainder. s-Testosterone, LH and FSH were decreased by the treatment. The men had no toxicological side effects or changes in libido and potency. During the recovery period sperm counts, sperm morphology, s-testosterone, LH and FSH returned to normal levels.A study was conducted to evaluate the effect of an oral gestagen (levo-norgestrel) in the same low doses comparable to those used in female contraceptive pills in combination with monthly injections of testosterone enanthate. 2 groups of 6 men, unpaid volunteers aged 25-45, were placed into 2 study groups. 1 group took a low-dose of levo-norgestrel orally and testosterone enanthate intramuscularly for 6 months; the other group took a high dose of the levo norgestrel combined with the same injection. 2 of the volunteers withdrew due to side effects. The 5 remaining on the low dose levo-norgestrel exhibited a reduction in sperm count, but no azoospermia. Those on the high dose experienced a more effective sperm reduction. None of the subjects suffered toxicological effects or changes in libido or potency. During the recovery period, sperm counts, sperm morphology, and sperm motility returned to normal. It is still unclear as to the doses at which this hormone combination will cause clinical sterility.

One daily dose of either 5 mg or 10 mg cyproterone acetate (CA) was administered to 2 groups of 4 fertile men for 6 months. The medication was preceded by a 3 months placebo period and followed by a recovery phase of 5 to 8 months. During CA-treatment the sperm count/ml decreased and the percentage of abnormal spermatozoa increased slightly (0.991 less than P less than 0.05). Sperm penetration assessed by the Kremer test did not show any decrease during treatment. Serum levels of testosterone and FSH decreased, but those of LH remained unchanged during treatment. Two pregnancies occurred after 13/4 and 51/2 months of CA-treatment. The serum-CA concentration in these 2 volonteers did not differ from that of the remainder. Three subjects who began the study were withdrawn because of depressive mood changes (2) and weakness combined with dizziness (1). Data from these subjects were not included. The results indicate that daily doses of 5 mg and 10 mg of cyproterone acetate are not effective as a male contraceptive.1 daily dose of either 5 mg or 10 mg cyproterone acetate (CA) was administered to 2 groups of 14 fertile men for 6 months in order to study the effects of low doses of CA. Semen samples were collected by masturbation at approximately 2-week intervals and analyzed for volume, sperm count and sperm morphology. Motility was evaluated subjectively by light microscopy. Sperm penetration was assessed by the Kremer Test (1965) after at least 16 weeks of treatment. General well-being, libido and sexual potency were assessed approximately every fortnight. The medication was preceded by a 3 month placebo period and followed by a recovery phase of 5-8 months. 7 volunteers completed the study. During CA treatment the sperm count/ml decreased and the percentage of abnormal spermatozoa increased slightly. Sperm penetration failed to show any decrease during treatment. Serum levels of testosterone and follicle stimulating hormone (FSH) decreased, but those of the luteinizing hormone (LH) remained unchanged during treatment. 2 pregnancies occurred after 1-3/4 and 5-1/2 months of CA treatment. The serum-CA concentration in these 2 volunteeers did not differ from that of the remainder of the volunteers. The results demonstrate that low doses of CA significantly decreased sperm count in 6 of 7 subjects but did not decrease it to the so-called "infertile" levels.

Testosterone tablets of crystal size 2–5 μm were administered orally for 10 dags to 3 human subjects with low endogenous serum testosterone (se-T) levels. Fifty mg testosterone increased se-T slightly, while one daily dose of 200 mg maintained the se-T level within normal range for men for more than 12 h. No cumulative effect was seen. Seven further subjects with low androgen production ingested 100 or 200 mg testosterone of crystal size 125–400 μm. Blood samples were taken frequently during the 24 h period following administration of the testosterone and se-T levels determined. Testosterone levels in serum increased in 6 patients and was maintained within the normal male range for 5–7 h. In one subject a slight but significant increase in se-T was observed although the level did not reach the normal male range. Although it has been shown that it is possible to use orally administered testosterone to maintain se-T levels in the normal male range, the convenience to the patient must be balanced against the cost and possible side effects of the large doses required.