Plasma Clozapine and N -Desmethylclozapine (Norclozapine) Concentrations and the Clozapine/Norclozapine Ratio : Effect of Dose, Sex, and Cigarette Smoking.

BACKGROUND: Smoking enhances plasma clozapine clearance, but the magnitude of the effect across the dose and age ranges is unclear. METHODS: We audited clozapine dose and predose plasma clozapine and N -desmethylclozapine (norclozapine) concentrations by sex and smoking habit in samples submitted for clozapine TDM, 1996-2017. RESULTS: There were 105,316/60,792 and 34,288/31,309 samples from male/female smokers/nonsmokers, respectively. There were distinct dose-median plasma concentration trajectories for male/female smokers/nonsmokers across the range <50 to >850 mg d -1 . For both sexes, the percentage difference in median plasma clozapine in nonsmokers versus smokers averaged 50% but was greatest for men (76%) and women (59%) in the 151 to 250 mg d -1 dose band. In men, the percentage difference declined steadily to 34% at doses of ≥850 mg d -1 . In women, the difference after falling initially remained relatively constant at 40% to 54%. The pattern in median plasma clozapine/norclozapine ratio by plasma clozapine concentration and dose groups was independent of sex and smoking habit, but increased with plasma clozapine concentration (higher ratio at higher concentrations) and also changed with dose. Median plasma clozapine concentration and median clozapine dose by sex and smoking habit were similar up to age 60 years. Proportional weight gain was similar over time in smokers and nonsmokers of either sex. IMPLICATIONS: These data explain the variations in the effect size of starting or stopping smoking on plasma clozapine concentration at constant dose reported in different studies. Changes in smoking habit in patients prescribed clozapine require prompt dose adjustment.

Effect of Coffee and Chocolate Ingestion on Clozapine Dose and on Plasma Clozapine and Norclozapine Concentrations in Clinical Practice.

BACKGROUND: Some reports point to dietary caffeine intake as a cause of increased plasma clozapine concentrations in certain patients. METHODS: We compared clozapine dose and plasma clozapine and N-desmethylclozapine (norclozapine) concentrations in male and female smokers and nonsmokers in relation to reported (i) coffee (caffeine) and (ii) chocolate (caffeine and theobromine) intake in samples submitted for clozapine therapeutic drug monitoring, 1993-2017. RESULTS: There was information on coffee ingestion for 16,558 samples (8833 patients) from males and 5886 samples (3433 patients) from females and on chocolate ingestion for 12,616 samples (7568 patients) from males and 4677 samples (2939 patients) from females. When smoking was considered, there was no discernible effect of either coffee or chocolate ingestion either on the median dose of clozapine or on the median plasma clozapine and norclozapine concentrations in men and in women. However, cigarette smoking was associated with higher coffee and chocolate consumption. Although male nonsmokers who reported drinking 3 or more cups of coffee daily had significantly higher median plasma clozapine and norclozapine concentrations than those who drank less coffee, they were also prescribed a significantly higher clozapine dose. There was no clear effect of coffee ingestion on plasma clozapine and norclozapine in female nonsmokers. IMPLICATIONS: Inhibition of clozapine metabolism by caffeine at the doses of caffeine normally encountered in those treated with clozapine is unlikely even in male nonsmokers. Measurement of plasma caffeine in an appropriate sample should be considered in any future investigation into a presumed clozapine-caffeine interaction.

The effectiveness of secondary-school based interventions on the future physical activity of adolescents in Aotearoa New Zealand: a modelling study.

BACKGROUND: Secondary schools are important settings for promoting varied physical activity (PA) opportunities for adolescents to promote PA throughout life. However, research on the effect of secondary school-based interventions on future PA is limited. This study examined the potential impact of secondary school-based interventions on the determinants of future PA participation of Aotearoa New Zealand (NZ) adolescents using simulated modelling. METHODS: We used data from a nationally representative sample of secondary school students (n = 5035) aged 12-17 between 2017 and 2020 in NZ. We modelled four secondary school-based interventions and their projected impact on five determinants of future PA. Modelled interventions were the technological augmentation of physical education (TAPE), a peer-led PA mentoring programme (PL), physically active learning (PAL) and the inclusion of a natural environment play area (NE). RESULTS: Total weekly PA increased the most from the NE intervention (+ 0.2 h/week), followed by TAPE (+ 0.08 h/week), PAL (+ 0.05 h/week) and PL (-0.06 h/week). Current number of PA settings increased the most in NE (+ 1.75 settings/week), followed by TAPE (+ 1.29 settings/week), PAL (+ 1.21 settings/week) and PL (+ 0.73 settings/week). Current number of PA types increased the most in NE (+ 1.57 types/week), followed by PL (+ 1.05 types/week), TAPE (+ 0.34 types/week) and PAL (+ 0.15 types/week). Physical literacy scores increased the most from PL (+ 3.6%), followed by PAL (+ 3.3%), TAPE (+ 0.43%) and NE (+ 0.12%). Social support scores increased the most from PAL (+ 5%), followed by PL (+ 1.9%), TAPE (+ 1.46%) and NE (+ 0.57%). CONCLUSIONS: On average, all interventions benefitted determinants of future PA participation to a small degree. Results show differing magnitudes of the intervention effect by determinant, indicating the complexities surrounding the promotion of PA adherence. Future interventions could be improved through detailed consultation alongside, and involving, adolescents and stakeholders within schools. Researchers should also prioritise the collection of longitudinal PA data and explore its connection with sociodemographic differences between adolescents.

Police, ambulance and psychiatric co-response versus usual care for mental health and suicide emergency callouts: A quasi-experimental study.

OBJECTIVE: Mental health-related calls to emergency services made via 111 (New Zealand) or 000 (Australia) often represent critical junctures for the person in crisis. Traditionally, police, ambulance and mental health services work separately to manage such emergencies. Sequential agency responses may be protracted and cause escalation. This study tests multi-agency co-response aiming for more integrated, faster, safer and less coercive management of mental health crises. METHODS: Immediate and 1-month outcomes of mental health emergency calls made to police and ambulance were compared according to whether they occurred on days with co-response availability. Outcomes measured included emergency department admission and waiting times, psychiatric admissions, compulsory treatment, use of force, detention in police cells and the time to resolution of the event. Relative risk estimates were constructed. RESULTS: A total 1273 eligible mental health emergency callouts occurred between March 2020 and March 2021 (38% coded 'mental health' emergencies, 48% suicide risk and 14% as 'other'), 881 on days with co-response availability and 392 on days without. Co-response interventions were resolved faster and were more likely to be community-based. Fewer than one-third (32%) led to emergency department admissions, compared with close to half (45%) on days without co-response (risk ratio: 0.7 [0.6, 0.8]). In the following month, the number of emergency department and mental health admissions reduced (p < 0.01 and 0.05, respectively). There were no statistically significant differences in use of force and few people were detained in police custody. CONCLUSION: Co-response intervention increased the likelihood of mental health crises being resolved in the community and reduced hospitalisations. Benefits were sustained at 1 month.

'An accident waiting to happen' - experiences of police officers, paramedics, and mental health clinicians involved in 911-mental health crises: a cross-sectional survey.

WHAT IS KNOWN ON THE SUBJECT: Police and ambulance staff are increasingly asked to help people experiencing mental health crises, but they often feel under-prepared. The single frontline service approach is time-intensive and risks a coercive pathway to care. The emergency department is the default location for transfers by police or ambulance involving a person involved in a mental health crisis, despite being viewed as suboptimal. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE: Police and ambulance staff struggled keeping up with the mental health demand, reporting inadequate mental health training, little enjoyment and negative experiences when trying to access help from other services. Most mental health staff had adequate mental health training and enjoyed their work, but many experienced difficulties getting help from other services. Police and ambulance staff found it hard to work with mental health services. WHAT ARE THE IMPLICATIONS FOR PRACTICE: The combination of limited training, poor interagency referral processes, and difficulties accessing support from mental health services means that when police and ambulance services attend mental health crises alone, distress may be heightened and prolonged. Enhanced mental health training for first responders and more streamlined referral processes may improve process and outcomes. Mental health nurses have key skills that could be utilized in assisting police and ambulance staff who attend 911 emergency mental health calls. New models such as co-response teams, whereby police, mental health clinicians and ambulance staff respond conjointly should be trialled and evaluated. ABSTRACT: INTRODUCTION: First responders are increasingly called to assist people experiencing mental health crises but little research exists canvassing multi-agency perspectives of such work. AIM/QUESTION: To understand the views of police officers, ambulance and mental health staff attending mental health or suicide-related crises in Aotearoa New Zealand and to discover how they experience current models of cross-agency collaboration. METHODS: A descriptive cross-sectional survey involving mixed methods. Quantitative data were analysed using descriptive statistics and free text by content analysis. RESULTS: Participants included 57 police officers, 29 paramedics and 33 mental health professionals. Mental health staff felt adequately trained, but only 36% described good processes for accessing inter-agency support. Police and ambulance staff felt undertrained and unprepared. Accessing mental health expertise was considered difficult by 89% of police and 62% of ambulance staff. DISCUSSION: Frontline services struggle managing mental health-related 911 emergencies. Current models are not working well. Miscommunication, dissatisfaction and distrust exist between police, ambulance and mental health services. CONCLUSION: The single-agency frontline response may be detrimental to service users in crisis and under-utilizes the skills of mental health staff. New ways of inter-agency cooperation are required, such as co-located police, ambulance and mental health nurses responding in partnership.

Determinants of Future Physical Activity Participation in New Zealand Adolescents across Sociodemographic Groups: A Descriptive Study.

This cross-sectional study aimed to explore various determinants of future physical activity (PA) participation in adolescents across sociodemographic groups. Sociodemographic characteristics (age, gender, ethnicity, deprivation status, physical disability status) were assessed in a national sample (n = 6906) of adolescents (12-17 years old) between 2017 and 2020 in New Zealand. The determinants of future PA participation chosen for analysis included current indicators of PA participation (i.e., total time, number of types, number of settings). We also examined widely recognised modifiable intrapersonal (i.e., physical literacy) and interpersonal (i.e., social support) determinants of current and future PA behaviour, along with indicators of PA availability issues. Older adolescents scored worse across all determinants of future PA than younger adolescents, with a key transition point appearing at 14-15 years of age. Maori and Pacific ethnicities scored best across each determinant category on average, with Asian populations scoring the worst. Gender diverse adolescents scored substantially worse than male and female adolescents across every determinant. Physically disabled adolescents scored worse than non-disabled across all determinants. Adolescents from medium and high deprivation neighbourhoods scored similarly across most determinants of future PA participation and both tended to score worse than people from low deprivation neighbourhoods. A particular focus on the improvement of future PA determinants is warranted within adolescents who are older, Asian, gender diverse, physically disabled, and from medium to high deprivation neighbourhoods. Future investigation should prioritise the longitudinal tracking of PA behaviours over time and develop interventions that affect multiple future PA determinants across a range of sociodemographic backgrounds.