A study comparing insulin lispro mix 25 with glargine plus lispro therapy in patients with Type 2 diabetes who have inadequate glycaemic control on oral anti-hyperglycaemic medication: results of the PARADIGM study.

AIMS: To test the hypothesis that initiation and intensification with 25% insulin lispro, 75% insulin lispro protamine suspension (LM25), is non-inferior to initiation and intensification with glargine + insulin lispro therapy on change from baseline in HbA(1c). METHODS: In this randomized, non-inferiority (margin of 0.4%), parallel, prospective, multi-country, 48-week, open-label study, patients (n = 426) with Type 2 diabetes inadequately controlled with oral anti-hyperglycaemic medications were assigned to either initiating therapy with one daily LM25 injection, progressing up to three daily injections (full analysis set n = 211; per protocol set n = 177) or initiating therapy with one daily glargine injection and progressing up to three daily insulin lispro injections (full analysis set n = 212; per protocol set n = 184). RESULTS: LM25 therapy was found to be non-inferior to glargine + insulin lispro therapy by study end (upper limit of 95% CI < 0.4), with a least-squares mean difference (95% CI) in HbA(1c) (LM25 minus glargine + insulin lispro) of -0.4 mmol/mol (95% CI -2.7 to 1.9); -0.04% (95% CI -0.25 to 0.17). No statistically significant differences between treatment groups were found in the percentage of patients achieving HbA(1c) targets or postprandial blood glucose levels. The increase in insulin dose, number of injections and weight change during the course of the study were similar in both groups. Patients in both groups experienced similar hypoglycaemia rates and safety profile. CONCLUSIONS: For patients with Type 2 diabetes inadequately controlled with oral anti-hyperglycaemic medications, glycaemic control when initiating and intensifying with LM25 therapy was found to be non-inferior to treatment with glargine + insulin lispro therapy.

A randomized non-inferiority study comparing the addition of exenatide twice daily to sitagliptin or switching from sitagliptin to exenatide twice daily in patients with type 2 diabetes experiencing inadequate glycaemic control on metformin and sitagliptin.

AIMS: To test the hypothesis that glycaemic control achieved when switching sitagliptin to exenatide twice daily plus metformin is non-inferior to adding exenatide twice daily to sitagliptin and metformin. METHODS: Patients with Type 2 diabetes inadequately controlled with sitagliptin plus metformin were randomly assigned to 20 weeks of treatment with twice-daily exenatide plus placebo and metformin (SWITCH, n = 127) or twice-daily exenatide plus sitagliptin and metformin (ADD, n = 128). RESULTS: Non-inferiority (0.4% margin) of SWITCH to ADD treatment, measured by change in HbA(1c) from baseline to week 20, was not shown {between-treatment difference in least-squares mean [95% CI 3 mmol/mol (0.30%)] [0.8-5.8 (0.07-0.53)]}. A greater reduction (P = 0.012) in HbA(1c) [least-squares mean (se)] was experienced by patients in the ADD group {-7 mmol/mol [-0.68%] [0.9 (0.08)]}, compared with those in the SWITCH group {-4 mmol/mol [-0.38%] [1.0 (0.09)]} and a greater proportion (P = 0.027) of patients in the ADD group (41.7%) reached < 7.0% (< 53 mmol/mol) HbA(1c) target, compared with those in the SWITCH group (26.6%) by week 20. Patients in the ADD group experienced greater fasting serum glucose (P = 0.038) and daily mean postprandial self-monitored blood glucose (P = 0.048) reductions, compared with patients in the SWITCH group, by week 20. Patients in both groups experienced a lower incidence of nausea and vomiting compared with previous exenatide studies. CONCLUSIONS: Non-inferiority of SWITCH to ADD treatment was not supported by the results of this study. In patients with Type 2 diabetes inadequately controlled with sitagliptin plus metformin, adding exenatide provided better glycaemic control than switching to exenatide. These results are consistent with the clinical approach that adding is better than switching to another oral anti-hyperglycaemic medication.

A randomized controlled trial of the effect of sublingual orally disintegrating olanzapine versus oral olanzapine on body mass index: the PLATYPUS Study.

BACKGROUND: Patients with schizophrenia and bipolar disorder have frequently reported weight gain during olanzapine treatment. Previous studies have observed a decrease in weight gain, or weight loss, in patients switching from standard olanzapine tablets (SOT) to orally disintegrating olanzapine (ODO) tablets. The primary objective of this study was to investigate the change in body mass index (BMI) in patients who had previously gained weight with SOT and continued with this therapy during the study period, compared with those patients who switched to ODO during the study period. METHODS: This was a 16-week, multicentre, randomized, double-blind, double-dummy, study of outpatients diagnosed with schizophrenia, schizoaffective disorder, related psychotic disorder or bipolar disorder, who were taking 5-20 mg SOT daily. Patients continued treatment with 5-20 mg olanzapine in a flexible single daily dose, and were randomized to either receive sublingual ODO plus an oral placebo, or sublingual placebo plus SOT. RESULTS: No statistically significant between group differences in mean change from baseline in BMI, weight or waist circumference were observed. Analysis of change in body weight from baseline, by pre-specified category (no change, loss of >or=1.5 kg, gain of >or=1.5 kg), revealed a significant difference between groups, favoring ODO patients, who also experienced a significant reduction in subjective appetite and better treatment compliance, compared to patients in the SOT group. CONCLUSIONS: In this study, patients treated with ODO experienced a similar mean change in BMI and weight from baseline, to those patients treated with SOT.

Consonant cluster development in two-year-olds: general trends and individual difference.

A holistic view of phonological development can be attained only through exploration of the relationship between universal developmental sequences, to establish a general pattern of development and individual learning and to provide information regarding variability. This study examined consonant cluster production, looking specifically at the relationship between general trends and individual differences as children acquire these sounds. The spontaneous speech of 16 normally developing Anglo-Australian 2-year-olds was elicited monthly for 6 months, and the corpus of 96 samples was examined using independent and relational phonological analyses. Data demonstrated that 2-year-olds were able to produce a range of consonant clusters in word-initial and word-final position, but few of the younger participants could produce consonant clusters correctly. Only half of the participants showed an increase in the percent of consonant clusters produced correctly over the 6-month period; however, their developing phonological maturity was revealed in the increase in the range and diversity of their repertoire of consonant clusters and by their closer approximations to the adult target. Specific findings of the study were compared to 10 trends for children's acquisition of consonant clusters emerging from the literature over the last 70 years.

Expression of MUL, a gene encoding a novel RBCC family ring-finger protein, in human and mouse embryogenesis.

We studied the expression of MUL, a gene encoding a novel member of the RING-B-Box-Coiled Coil family of zinc finger proteins that underlies the human inherited disorder, Mulibrey nanism. In early human and mouse embryogenesis MUL is expressed in dorsal root and trigeminal ganglia, liver and in epithelia of multiple tissues.

Understanding and improving medical student specialty choice: a synthesis of the literature using decision theory as a referent.

BACKGROUND: As emphasis in medicine has shifted to increasing the number of physicians who choose primary care specialties, many studies of medical specialty choice have been conducted. Although researchers have approached the topic in a number of ways, most approaches have tended to focus on narrow elements of the choice, such as the effect of programs or curricula. A more comprehensive approach is possible by fitting the process to a preexisting broad theoretical framework. SUMMARY: This synthesis of the literature examines specialty choice from the perspective of decision theory--with its aims of understanding how decisions are made, providing information about the quality of decisions, and improving the decision-making process. CONCLUSION: This approach has the potential to not only help deconstruct the process of decision making regarding specialty choice but also uncover information about the best ways to help medical students learn to make wise decisions.

Teaching children about health: an example of secondary gain in an academic-community partnership.

CONTEXT: The Partners in Health Education (PHE) program is an elective that pairs first and second year medical students with local classroom teachers to promote health messages to students in kindergarten through grade eight. Designed with the primary goal of helping medical students improve their communication skills through the process of teaching children about health, the PHE program has secondary goals of supporting community teachers in their efforts to promote health and of teaching children about health and the prevention of disease and injury. This report contains the results of the assessment of program impact on the school children. METHODS: A total of 327 elementary grade students in 14 experimental classrooms and 13 comparison classrooms comprised the participants for the study. Students were individually interviewed twice over an eight-week period using a structured interview form designed to capture self-report information about health and healthy living. Repeated measures analysis of variance was conducted. The effect of interest in each case was the treatment x time interaction. RESULTS: There were significant treatment x time interactions for several measures of children's reported knowledge and attitudes about health. DISCUSSION: Although designed primarily to help medical students improve their communication skills, the PHE program produced a secondary gain such that elementary students in participating classrooms reported learning more about health than did students in comparison classrooms. Programs such as PHE can provide ways to meet the goal of helping children become empowered to take charge of their own health and to make healthy choices.

Realizations of consonant clusters by children with phonological impairment.

Children with phonological impairment frequently have difficulty producing consonant clusters. Speech pathologists often use phonological processes to describe children's productions of consonant clusters, a commonly used description being cluster reduction. However, this description does not adequately address children's differing realizations of consonant clusters. The purpose of this paper is to develop and refine methods for the characterization of realizations of consonant clusters. The work of Greenlee (1974) and Chin and Dinnsen (1992) has been extended by examining the effect of syllable position, number of elements and constituents on children's realizations of consonant clusters. Specifically, word-initial fricative clusters, stop clusters, three element fricative + stop clusters, and word-final nasal clusters and fricative + stop clusters were examined. The results for 40 phonologically impaired children between the ages of 3;6 and 5;0 years are compared with those of Chin and Dinnsen (1992). The relationships found between child and adult representations of clusters suggest the importance of considering syllable position, number of elements and the constituents of consonant clusters when analysing phonologically impaired children's speech sounds.

Adults with acquired hearing loss: identification and referral patterns of community health workers.

Community health workers in one health region of New South Wales were surveyed about their criteria and referral patterns to identify and assist adults with acquired hearing losses. Reported or observed communication problems were the most commonly used criteria for identifying hearing loss, suggesting that a failure model was being utilised. Given that the literature has previously demonstrated reluctance on the part of individuals with acquired hearing loss to report their hearing difficulties, the implications of these results are discussed. Clients suspected of having acquired hearing losses were usually referred to their doctors for further investigation and treatment. Other hearing help services were not systematically utilised. Alternative strategies for identifying and managing acquired hearing loss at the community level are needed.