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The paper proposes an optimal response‐adaptive procedure for a general class of responses using a combination of two clinically relevant optimality criteria. We provide a thorough development for trials involving two treatments and sketch the possible extension for multiple treatments. Some related asymptotic results are worked out. We provide simulation studies to compare the performance of the proposed procedure with some of the existing competitors. We illustrate our methodology on data from a real clinical trial.

A randomized two‐stage adaptive design is proposed and studied for allocation of patients to treatments and comparison in a phase III clinical trial with survival time as treatment responses. We consider the possibility of several covariates in the design and analysis. Several exact and limiting properties of the design and the follow‐up inference are studied, both numerically and theoretically. The applicability of the proposed methodology is illustrated by using some real data.

Context: Pyridostigmine bromide (PB) is a quaternary ammonium compound and has been approved as a pretreatment drug against toxic organophosphorous (OP) compounds. The stressful demands of modern military activity include a broad range of activities at extreme cold temperatures along with various physical activities. Objective: The effect of "sign free" dose of PB (0.075 mg/kg body weight) against a toxic OP compound diisopropyl fluorophosphate (DFP) was reassessed in rats. Electrocardiographic (ECG) studies in hypothermic and pretreatment conditions were undertaken to assess the cardioprotective role of PB. Total Antioxidant Status (TAS) was quantified to assess the degree of oxidative stress imposed under such conditions. Possible protective role of pyridostigmine in rat lymphocytes was also determined.Materials& Methods: TAS was estimated spectrophotometrically and the expression of interferon-γ (IFNγ) was measured by Fluorescence Activated Cell Sorting. ECG was monitored by standard protocol.Results: ECG recording showed that the PR and QT interval progressively increased along with widening of QRS complex. There was a progressive fall in heart rate as the body temperature decreased. TAS significantly decreased (p≤0.001) in hypothermic conditions and when pretreated with sign free dose of PB before cold induction (p≤0.001). Following immunostaining of lymphocytes by FITC conjugated mouse anti-rat IFNγ monoclonal antibody, 9.1% of lipopolysaccharide elicited parent cells showed positive IFNγ expression. Hypothermic stress inhibited IFNγ expression (3.6% of parent cells) which was recovered to 6.8% upon pre-treatment with sign-free dose of pyridostigmine. Conclusion: This study is indicative of a possible protective role of PB against hypothermic stress.

Context: Pyridostigmine bromide (PB) is a quaternary ammonium compound and has been approved as a pretreatment drug against toxic organophosphorous (OP) compounds. The stressful demands of modern military activity include a broad range of activities at extreme cold temperatures along with various physical activities. Objective: The effect of "sign free" dose of PB (0.075 mg/kg body weight) against a toxic OP compound diisopropyl fluorophosphate (DFP) was reassessed in rats. Electrocardiographic (ECG) studies in hypothermic and pretreatment conditions were undertaken to assess the cardioprotective role of PB. Total Antioxidant Status (TAS) was quantified to assess the degree of oxidative stress imposed under such conditions. Possible protective role of pyridostigmine in rat lymphocytes was also determined. Materials& Methods: TAS was estimated spectrophotometrically and the expression of interferon-γ (IFNγ) was measured by Fluorescence Activated Cell Sorting. ECG was monitored by standard protocol. Results: ECG recording showed that the PR and QT interval progressively increased along with widening of QRS complex. There was a progressive fall in heart rate as the body temperature decreased. TAS significantly decreased (p≤0.001) in hypothermic conditions and when pretreated with sign free dose of PB before cold induction (p≤0.001). Following immunostaining of lymphocytes by FITC conjugated mouse anti-rat IFNγ monoclonal antibody, 9.1% of lipopolysaccharide elicited parent cells showed positive IFNγ expression. Hypothermic stress inhibited IFNγ expression (3.6% of parent cells) which was recovered to 6.8% upon pre-treatment with sign-free dose of pyridostigmine. Conclusion: This study is indicative of a possible protective role of PB against hypothermic stress.

Background: A range of evidence for the effectiveness of one-to-one peer support in mental health services is emerging. Levels of engagement with peer support vary with limited studies showing few individual participant characteristics predicting engagement. Implementation factors that might predict engagement have not been considered. Methods: Data were analysed from the intervention arm of the ENRICH trial of one-to-one peer support for discharge from acute psychiatric inpatient care. Two outcomes were considered: (1) a measure of 'engaged with peer worker'; (2) number of face-to-face contacts with peer worker post-discharge. Two sets of independent variables were analysed against each outcome: (1) pre-randomisation participant characteristics; (2) implementation factors measured pre-discharge. Analyses used logistic and zero-inflated negative binomial regression models according to outcome structure. Results: Data were analysed for 265 participants randomised to peer support who had a known peer worker. Non-heterosexual participants had increased odds of engaging with peer support compared to heterosexual participants, OR = 4.38 (95% CI: 1.13, 16.9, p = .032). Longer duration of first contact with peer worker ( OR = 1.03, 95% CI: 1.00, 1.04, p < .001) and more relationship building activities in the first contact ( OR = 1.4, 95% CI: 1.13, 1.85, p = .004) were associated with greater odds of engaging with peer support. Analysis of number of contacts post-discharge showed consistent findings. Conclusions: Implementation of peer support should include a focus on relationship building in the first session of peer support. The potential for peer support to break down barriers to accessing mental health services experienced by people from marginalised communities warrants further investigation.