Abdominal stimulation for ventilation in tetraplegia

The respiratory system is highly compromised after a tetraplegic spinal cord injury due to paralysis of the major breathing muscles. As a result mechanical ventilation is often required and respiratory complications are a major cause of rehospitilisation, morbidity, and early mortality. Functional electrical stimulation (FES) applied acutely to the abdominal wall muscles in synchrony with a patient's volitional exhalation has been shown to improve breathing volumes and the ability to cough in spontaneously breathing tetraplegic patients. It has also been used acutely to improve breathing volumes in otherwise mechanically ventilated patients. The effect of using abdominal FES (AFES) chronically on AFES-assisted and unassisted respiratory function is currently unknown. To support clinical adoption of AFES practical systems are required. Systems that synchronise AFES with exhalation automatically have been developed but they have relied on invasive respiratory sensors. In the first clinical study of this thesis twelve tetraplegic patients who could breathe spontaneously completed a three week AFES training programme in addition to a one week pre-training control period and a three week post-training follow up period. The results showed a significant increase in \ac{afes}-assisted forced vital capacity (FVC), and unassisted FVC, peak expiratory flow (PEF), and cough peak flow (CPF) throughout the training period. AFES-assisted PEF and CPF tended to increase over the same period, but the increase was not significant. The difference between unassisted and AFES-assisted measures did not change. Overall, there were limited changes in the outcome measures during the control and follow up periods, which suggests that the changes in outcome measures observed during the training period were a response to training. In the second clinical study daily sessions of AFES-breathing were combined with the standard of care during the process of weaning a single tetraplegic patient from mechanical ventilation. The results showed that the approach was feasible: AFES acutely increased the duration of ventilator free breathing at the start of the weaning process and daily ventilator free breathing improved considerably during two four-week long periods of daily AFES-assisted breathing. In the final study breathing data was recorded from ten healthy volunteers using a spirometer (the current standard), a nasal thermocouple, and piezoelectric belts wrapped around the chest and abdomen. An algorithm was written for each of the sensors so that they could be used to trigger stimulation during quiet breathing. The thermocouple system, followed by the chest belt system, were shown to be the most suitable replacement sensors for the spirometer. The results of this thesis suggest three different applications of AFES in tetraplegia: a neurorehabilitation device that can be used to improve unassisted respiratory function in spontaneously breathing tetraplegics; a neuroprosthesis device that could be used to assist spontaneously breathing tetraplegics in times of respiratory distress, e.g. during recovery from respiratory infection; and as a method of weaning tetraplegic patients from mechanical ventilation. The realisation of these applications will be assisted by the non-invasive respiratory sensor algorithms developed in this thesis. Collectively these results have demonstrated the feasibility of several new areas of future research, which could ultimately be of great benefit to the health of patients with tetraplegia

Cognitive Specificity in Trait Anger in Relation to Depression and Anxiety in a Community Sample

The current research explored 16 of Young's schemas in relation to trait anger and to anxiety and depression symptoms among 262 non-clinical Australian adults with low-level symptomatology and average anger levels. The study partially replicated previous work with a sample of Spanish students that investigated the relationship between anger, depression, and anxiety and Young's schemas. Predictions derived from Beck's notion of cognitive specificity were examined using structural equation modelling and showed that of the sixteen schemas, Vulnerability was linked to anxiety, Social Isolation and Enmeshment were linked to depression, and Entitlement, Insufficient Self-Control, Mistrust and Abuse, Subjugation (negatively), and Abandonment were linked to anger. The discrepancies between these and the Spanish findings and the difficulties of other researchers in establishing higher order aggregations of Young's schemas prompted further consideration of the range of such schemas with respect to anger, depression, and anxiety, and the possibility that sample characteristics may play a critical role in determining the varying affect-schema relationships. © 2011 The Australian Psychological Society

An Algorithm for Fitting Mixtures of Gompertz Distributions to Censored Survival Data

We consider the fitting of a mixture of two Gompertz distributions to censored survival data. This model is therefore applicable where there are two distinct causes for failure that act in a mutually exclusive manner, and the baseline failure time for each cause follows a Gompertz distribution. For example, in a study of a disease such as breast cancer, suppose that failure corresponds to death, whose cause is attributed either to breast cancer or some other cause. In this example, the mixing proportion for the component of the mixture representing time to death from a cause other than breast cancer may be interpreted to be the cure rate for breast cancer (Gordon,'90a and'90b). This Gompertz mixture model whose components are adjusted multiplicatively to reflect the age of the patient at the origin of the survival time, is fitted by maximum likelihood via the EM algorithm (Dempster, Laird and Rubin,'77). There is the provision to handle the case where the mixing proportions are formulated in terms of a logistic model to depend on a vector of covariates associated with each survival time. The algorithm can also handle the case where there is only one cause of failure, but which may happen at infinity for some patients with a nonzero probability (Farewell,'82).

Understanding male domestic partner abusers

Research in the past decade has found that certain ways of responding to domestic partner abusers, particularly psycho-educational approaches, can be effective in modifying abusive behaviours. The study described in this paper sought to classify male domestic partner abusers by certain identified characteristics and determine whether they responded differently to a Men's Behaviour Change Program conducted by community agencies in regional Victoria. It was found that some types of male abusers appeared to derive greater benefits from the standard 12-week program than others. Those with antisocial personality disorders tended not to respond favourably. Further research work is now required to identify interventions that will be successful with abusers who have significant antisocial personalities

The longitudinal effects of midwife-led postnatal debriefing on the psychological health of mothers

To assess the effect of midwife-led postpartum debriefing on psychological variables, 149 women were recruited in the third trimester of their pregnancy and were randomly assigned to treatment and control conditions. Women in the treatment group received midwife-led postpartum debriefing within 3 days postpartum, whereas women in the control group did not receive formalised debriefing. Background information and psychological variables were assessed in the prepartum, and birthing information was gathered 2 days postpartum. The psychological variables, plus a measure of birth trauma, were re-assessed at 1 month, and again, together with a measure of parenting stress, at 3 months postpartum. Although the majority of women reported positively on their debriefing experience, statistical analyses indicated that only on the measure of dyadic satisfaction was there some suggestion that debriefing was effective. There were no significant differences between the treatment and control groups on measures of personal information, depression, anxiety, trauma, perception of the birth, or parenting stress at any assessment points, postpartum. On the other hand, the effect of medical intervention on women's perceptions of their birthing was evident, with women who experienced more medical intervention reporting more negative perceptions of their birthing than women who had experienced less medical intervention. Surprisingly, this difference was more marked among the women who had been debriefed than among the control group. Generally, the results did not support midwife-led debriefing as an effective intervention postpartum. © 2006 Society for Reproductive and Infant Psychology.C

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease:results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease:results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

The relationship between familiarity, gender, disagreement, and status and bouts of solitary and joint laughter

The current research treated laughter as an indexical with two closely allied properties: to designate talk as non-serious and to serve as a mode of address signalling a preference for solidarity. These properties gave rise to four discrete forms of laughter bout, solitary speaker, solitary listener, speaker-initiated joint, and listener-initiated joint laughter, which were examined using 55 same-gender pairs discussing three choice dilemma items. By exploring the associations between the wider contextual factors of familiarity, gender, disagreement and status, and the frequencies of each form of bout within the dyad, it was hoped to establish whether laughter was related to how participants modulated their social relationships. Neither familiarity nor disagreement had any effect on any of the forms of laughter bout, while females were found to demonstrate higher frequencies of joint speaker laughter than males. In unequal status pairs, high status female staff joined in the laughter of their low status female student interlocutors less often than the reverse, a finding comparable with the exchange of other terms of address, such as second person pronouns in European languages. It was concluded that joint laughter was a signal of solidarity and solitary speaker laughter was a declared preference for solidarity, but the significance of solitary listener laughter, beyond an acknowledgement of the speaker’s non-serious talk, remained less clear. It was also noted that norms associated with the setting and topic of interaction were influential in determining the extent to which laughter would be used to modulate the relationships between interlocutors. © 2022, The Author(s)