Novel Candidate Regulators and Developmental Trajectory of Pituitary Thyrotropes.

The pituitary gland regulates growth, metabolism, reproduction, the stress response, uterine contractions, lactation, and water retention. It secretes hormones in response to hypothalamic input, end organ feedback, and diurnal cues. The mechanisms by which pituitary stem cells are recruited to proliferate, maintain quiescence, or differentiate into specific cell types, especially thyrotropes, are not well understood. We used single-cell RNA sequencing in juvenile P7 mouse pituitary cells to identify novel factors in pituitary cell populations, with a focus on thyrotropes and rare subtypes. We first observed cells coexpressing markers of both thyrotropes and gonadotropes, such as Pou1f1 and Nr5a1. This was validated in vivo by both immunohistochemistry and lineage tracing of thyrotropes derived from Nr5a1-Cre; mTmG mice and demonstrates that Nr5a1-progenitors give rise to a proportion of thyrotropes during development. Our data set also identifies novel factors expressed in pars distalis and pars tuberalis thyrotropes, including the Shox2b isoform in all thyrotropes and Sox14 specifically in Pou1f1-negative pars tuberalis thyrotropes. We have therefore used single-cell transcriptomics to determine a novel developmental trajectory for thyrotropes and potential novel regulators of thyrotrope populations.

Achievements and challenges during the development of an advance care planning program.

A nationwide program to promote preparation of advance care plans (AC Plans) was introduced in Canterbury, New Zealand, in 2013. The program was developed by local facilitators who provided support and organised education seminars and an accredited training program for health-care professionals. Information and templates for an AC Plan were available to these professionals and the community on local health-care websites and secure online systems designed to allow plans to be viewed across all health-care sectors. The number of AC Plans prepared has increased steadily, although people in minority ethnic populations or in the most deprived socioeconomic quintile are less likely to have a plan. While nurses have become the predominant group guiding people through the process of preparing an AC Plan, the involvement of staff in residential care homes has remained low. Local audit showed that 82% of people with an AC Plan died in a community setting, frequently their preferred place of death.

Mental health presentations to Christchurch Hospital Emergency Department during COVID-19 lockdown.

OBJECTIVE: To describe mental health presentations to a tertiary ED in New Zealand during a national COVID-19 lockdown. METHODS: A retrospective, comparative cohort study in Christchurch Hospital, New Zealand. RESULTS: There was a 3510 (37%)-patient decrease in all presentations to Christchurch Hospital ED during the 5-week COVID-19 lockdown period from 26 March 2020 to 28 April 2020, compared to a 111 (1.2%)-patient decrease in the same time period in the previous year (P < 0.00001). There is usually a seasonal reduction in mental health attendances at this time of year compared to the weeks before. In 2019, there was a 49 (9.8%)-patient reduction in mental health presentations, whereas in 2020 there was a 193 (34%)-patient reduction (P < 0.001). In 2020, the proportion of mental health attendances compared to all ED attendances during the 5-week lockdown period was similar to the 5-week pre-lockdown period (564/9460 vs 371/5950, P = 0.48). The proportion of mental health patients presenting due to overdose increased by 6.5% (158/564 vs 128/371, P = 0.035); those due to self-harm increased by 3.5% (35/564 vs 36/371, P = 0.049). The proportion of mental health presentations due to anxiety, depression and other non-self-harm/overdose complaints decreased by 10% (371/564 vs 207/371, P = 0.002). The proportion of overdoses of paracetamol and ibuprofen increased by 13.4% during lockdown (22/158 vs 35/128, P = 0.005). CONCLUSIONS: During the COVID-19 lockdown, both overall ED presentations as well as mental health-related presentations decreased. There was a relative increase in overdoses and self-harm, particularly involving paracetamol and ibuprofen.

RIP1 inhibition blocks inflammatory diseases but not tumor growth or metastases.

The kinase RIP1 acts in multiple signaling pathways to regulate inflammatory responses and it can trigger both apoptosis and necroptosis. Its kinase activity has been implicated in a range of inflammatory, neurodegenerative, and oncogenic diseases. Here, we explore the effect of inhibiting RIP1 genetically, using knock-in mice that express catalytically inactive RIP1 D138N, or pharmacologically, using the murine-potent inhibitor GNE684. Inhibition of RIP1 reduced collagen antibody-induced arthritis, and prevented skin inflammation caused by mutation of Sharpin, or colitis caused by deletion of Nemo from intestinal epithelial cells. Conversely, inhibition of RIP1 had no effect on tumor growth or survival in pancreatic tumor models driven by mutant Kras, nor did it reduce lung metastases in a B16 melanoma model. Collectively, our data emphasize a role for the kinase activity of RIP1 in certain inflammatory disease models, but question its relevance to tumor progression and metastases.

Hospital avoidance: an integrated community system to reduce acute hospital demand.

BACKGROUND: Growth in emergency department (ED) attendance and acute medical admissions has been managed to very low rates for 18 years in Canterbury, New Zealand, using a combination of community and hospital avoidance strategies. This paper describes the specific strategies that supported management of acutely unwell patients in the community as part of a programme to integrate health services. INTERVENTION: Community-based acute care was established by a culture of close collaboration and trust between all sectors of the health system, with general practice closely involved in the design and management of the services, and support provided by hospital specialists, coordination and diagnostic units, and competent informatics. Introduction of the community-based services was aided by a clinical guidance website and an education programme for general practice teams and allied health professionals. OUTCOMES: Attendance at EDs and acute medical admission rates have been held at low growth and, in some cases, shorter lengths of hospital stay. This trend was especially evident in elderly patients and those with ambulatory care sensitive or chronic disorders. CONCLUSIONS: A system of community-based care and education has resulted in sustained gains for the Canterbury health system and freed-up hospital resources. This outcome has engendered a sense of empowerment for general practice teams and their patients.

The challenges of managing gout in primary care: Results of a best-practice audit.

BACKGROUND AND OBJECTIVES: The aim of this project was to determine the effects of a package of care for gout in primary care. METHOD: An audit of gout management in a single rural medical practice was undertaken before (in 2012) and after (in 2015) the introduction of the package of care reflecting guidelines in gout management. RESULTS: There was a statistically significant increase in the number of individuals commenced on allopurinol ≤100 mg/d and a decrease in the number commenced on allopurinol ≥200 mg/d (P <0.001). The number of times each patient had serum urate tested between 2012 and 2015 (median [range] 1 [0-3] versus 2 [0-10], respectively; P <0.001). Of those individuals who had at least one serum urate measurement, the number of individuals who were never at target urate was 43 out of 67 (64.2%) in 2012, compared with 52 out of 133 (39.1%) in 2015 (P = 0.001). DISCUSSION: A package of care can improve adherence to gout management guidelines in primary care.

The impact of the Canterbury earthquakes on dispensing for older person's mental health.

OBJECTIVE: To evaluate the impact of the Canterbury earthquakes on the mental health of older people by examining dispensing patterns of psychotropic medication. METHOD: Dispensing data from community pharmacies for antidepressants, antipsychotics, anxiolytics, and sedative/hypnotics are routinely recorded in a national database. Longitudinal data are available for residents of the Canterbury District Health Board (DHB) (n = 67 760 at study onset) and the rest of New Zealand (n = 469 055 at study onset). We compared older age dispensing data between 2008 and 2018 for Canterbury DHB with older age dispensing data nationally in order to assess the impact of the Canterbury earthquakes on the mental health of older persons. RESULTS: Older age residents of Canterbury are dispensed antidepressants, antipsychotics, and anxiolytics at higher rates than national comparators, but this finding predated the onset of the earthquakes. Short-term increases in anxiolytic and sedative/hypnotic dispensing occurred for the month following the February 2011 earthquake. No other short- or longer-term increases in dispensing of psychiatric medication were present. CONCLUSION: The February 2011 Canterbury earthquake caused a short-term increase in dispensing of anxiolytics and sedative/hypnotics. No longer-term effects on dispensing were observed. This suggests that older persons sought assistance for insomnia and anxiety in the aftermath of the most devastating earthquake, but longer-term rates of clinically significant anxiety and depression for older persons did not increase as a consequence of the earthquakes sequence.

Impact of integrated health system changes, accelerated due to an earthquake, on emergency department attendances and acute admissions: a Bayesian change-point analysis.

OBJECTIVE: To chart emergency department (ED) attendance and acute admission following a devastating earthquake in 2011 which lead to Canterbury's rapidly accelerated integrated health system transformations. DESIGN: Interrupted time series analysis, modelling using Bayesian change-point methods, of ED attendance and acute admission rates over the 2008-2014 period. SETTING: ED department within the Canterbury District Health Board; with comparison to two other district health boards unaffected by the earthquake within New Zealand. PARTICIPANTS: Canterbury's health system services ∼500 000 people, with around 85 000 ED attendances and 37 000 acute admissions per annum. MAIN OUTCOME MEASURES: De-seasoned standardised population ED attendance and acute admission rates overall, and stratified by age and sex, compared before and after the earthquake. RESULTS: Analyses revealed five global patterns: (1) postearthquake, there was a sudden and persisting decrease in the proportion of the population attending the ED; (2) the growth rate of ED attendances per head of population did not change between the pre-earthquake and postearthquake periods; (3) postearthquake, there was a sudden and persisting decrease in the proportion of the population admitted to hospital; (4) the growth rate of hospital admissions per head of the population declined between pre-earthquake and postearthquake periods and (5) the most dramatic reduction in hospital admissions growth after the earthquake occurred among those aged 65+ years. Extrapolating from the projected and fitted deseasoned rates for December 2014, ∼676 (16.8%) of 4035 projected hospital admissions were avoided. CONCLUSIONS: While both necessarily and opportunistically accelerated, Canterbury's integrated health systems transformations have resulted in a dramatic and sustained reduction in ED attendances and acute hospital admissions. This natural intervention experiment, triggered by an earthquake, demonstrated that integrated health systems with high quality out-of-hospital care models are likely to successfully curb growth in acute hospital demand, nationally and internationally.

The impact of the Canterbury earthquakes on prescribing for mental health.

OBJECTIVE: The aim of this study is to evaluate the impact of the Canterbury earthquakes on the mental health of the local population by examining prescribing patterns of psychotropic medication. METHOD: Dispensing data from community pharmacies for antidepressants, antipsychotics, anxiolytics and sedatives/hypnotics are routinely recorded in a national database. The close relationship between prescribing and dispensing provides the opportunity to assess prescribing trends for Canterbury compared to national data and therefore examines the longitudinal impact of the earthquakes on prescribing patterns. RESULTS: Short-term increases in the use of anxiolytics and sedatives/hypnotics were observed after the most devastating February 2011 earthquake, but this effect was not sustained. There were no observable effects of the earthquakes on antidepressant or antipsychotic dispensing. CONCLUSION: Short-term increases in dispensing were only observed for the classes of anxiolytics and sedatives/hypnotics. No sustained changes in dispensing occurred. These findings suggest that long-term detrimental effects on the mental health of the Canterbury population were either not present or have not resulted in increased prescribing of psychotropic medication.

Towards integrated person-centred healthcare - the Canterbury journey.

The Canterbury District Health Board (DHB) is the second largest by population (over half a million people) and by geographical area of the 20 DHBs in New Zealand, which were established in 2000. The DHB directly employs over 9,500 staff, and a similar number work in non-governmental sector and private based DHB-funded health services, which includes general practice. The DHB is government funded to plan the strategic direction for health and disability services in Canterbury; fund the majority of health and disability services provided in Canterbury; provide health and disability services primarily for the population of Canterbury but also extensive tertiary services for the South Island and, in some cases, for residents of the lower North Island; and promote, protect and improve the health and wellbeing of the Canterbury population.

Keep on brushing: a longitudinal study of motivational text messaging in young adults aged 18-24 years receiving Work and Income Support.

OBJECTIVES: Using text messaging, underpinned by the Health Belief Model, this study aimed to improve tooth brushing frequencies among unemployed young adults aged 18-24 years. METHODS: Set within Work and Income's Linwood Community Link office (one Christchurch branch of the New Zealand Government's employment and beneficiary services), unemployed young adults aged 18-24 years with access to a mobile phone were recruited using either a purpose-built computer kiosk or Work and Income's Facebook site. Participants completed a baseline survey and then received and responded to a series of motivational text messages over 10 weeks. Self-reported tooth brushing frequency was the primary outcome variable. Important socio-demographic (age, gender, ethnicity, employment status) and method-specific (level of attrition, distribution of successful text messages deliveries, active withdrawal) variables were also collected. Longitudinal analyses of these responses employed generalized estimating equation (GEE) models. RESULTS: Four hundred and three registered for the trial, of whom 171 (42%) were eligible. Self-reported tooth brushing twice or more per day increased from 51% at baseline to 70% at week 3, 74% at week 6, and 73% at week 9 - an increase significant in crude (P<0.001) and adjusted (P<0.001) GEE analyses. No important differences were noted between age, gender, or ethnic groups, although attrition was relatively high with only 26% participating by week 9. However, no evidence of differential attrition was observed. CONCLUSIONS: Invention through motivational text messaging improved the measured oral health self-care behavior in a hard-to-reach group carrying a disproportionately heavy oral health burden. This intervention warrants further investigation.

Improving the evidence-base for access to primary health care in Canterbury: a panel study.

OBJECTIVE: Despite many reforms and initiatives, inequities in access to primary health care remain. However, the concept of 'access' and its measurement is complex. This paper aims to provide estimates of general practice visit frequencies for 'attenders' (those who seek consultation) and the proportion of 'non-attenders' (those who never seek consultation) of primary health care services. METHODS: A panel study of people enrolled within a large primary health care organisation of affiliated general practices. Standard and zero-inflated regression models were assessed. RESULTS: 980,918 visits were made by 388,424 people, averaging 2.64 visits/person/year. The zero-inflated negative binomial model was superior, and significant age, gender and ethnic differences were observed in attender and non-attender profiles. More Asian (21.0%), Pacific (19.6%) and Maori (17.1%) people were non-attenders than European/Other (9.0%) people. Among attenders, males, Asian and Pacific people, and young to middle-aged adults, generally had relatively lower visit rates. CONCLUSIONS: Interpretation of utilisation data must be made with caution because of two distinct characteristics: the differential rates of non-attenders and the highly dispersed distribution of attenders. IMPLICATIONS: Improved understanding of differential non-attender rates and attender visit distributions by demographic factors needs to be considered when addressing improved access to general practice services.

The effects of location and low-molecular-weight heparin administration on deep vein thrombosis outcomes in trauma patients.

BACKGROUND: Deep vein thrombosis (DVT) is common after trauma. Pulmonary embolism (PE) is a feared complication of DVT. Standard doses of low-molecular-weight heparin (LMWH) are commonly used to prevent and treat DVT and PE. There is variable bioavailability of LMWH with standard therapy. The traditional concept that below-knee DVT is associated with a lower risk of subsequent PE may result in less aggressive therapy. The purposes of this study were to assess the rates of PE in above-knee versus below-knee DVT and longitudinally evaluate outcomes of DVT treated with LMWH therapy. METHODS: This was a retrospective review of patients at a university Level I trauma center during the years 2005 through 2010. Patients diagnosed with lower-extremity DVT were included in this study. Patients were classified by location of lower-extremity DVT and type of LMWH therapy received. All high-risk trauma patients were evaluated with weekly duplex Doppler ultrasonography. All duplex studies were reviewed for DVT resolution or improvement. Symptomatic patients were evaluated with computed tomographic angiography to rule out PE. Demographics, total length of hospital stay, length of intensive care unit stay, and Injury Severity Score (ISS) were collected. RESULTS: Three-hundred eight trauma patients with lower-extremity DVT were included. More patients developed below-knee DVT (65.6%) compared with above-knee DVT (34.4%). Increased length of hospital stay, intensive care unit stay, and higher ISS were noted in patients with above-knee DVT. More patients had below-knee DVT in the prophylactic dosing group. With LMWH therapy, three PEs occurred in patients in the prophylactic dosing group with below-knee DVT, and no PEs occurred in the therapeutic treatment group. The incidence of PE between patients with below-knee DVT compared with above-knee DVT overall was not different (3.3% and 4.7%, p = 0.59). To assess DVT outcomes, 157 of the 308 patients had serial duplex studies following diagnosis of lower-extremity DVT. The number of patients receiving either therapeutic or prophylactic LMWH was similar (51% and 49%). There was no difference in rates of resolution or improvement between LMWH dosing groups or location of DVT. CONCLUSION: In screened trauma patients, below-knee DVT is more common than above-knee DVT. There was no difference in the incidence of PE between groups. Standard prophylactic and therapeutic dosing of LMWH does not affect the rates of resolution or improvement of lower-extremity DVT. Rates of resolution and improvement of DVT is not dependent of location of lower-extremity DVT. LEVEL OF EVIDENCE: Therapeutic study, level IV; epidemiologic study, level III.

Appetite for life: an evaluation of a primary care lifestyle programme.

INTRODUCTION: Appetite for Life is a six-week primary care-based programme for women who are overweight, and aims to achieve long-term health gain through establishing healthy eating and physical activity patterns and a healthier weight. AIM: To evaluate the outcomes of Appetite for Life, a primary care-based healthy lifestyle programme for women who are overweight. METHODS: Two hundred and sixty-one women enrolled and consented to take part in the six-week Appetite for Life programme via general practice and were followed for 12 months. Eating behaviours and physical activity levels were measured at baseline, six weeks, six months and 12 months. Anthropometric and biomedical data was collected at visits to the participants' general practitioners at baseline and 12 months. RESULTS: Positive lifestyle changes were reported that were sustained for the duration of the 12-month follow-up period. Participants reported an increase in intake of fruit and vegetables, dairy products, healthy fats and an increased level of physical activity. There was also an increase in reported enjoyment and participation in exercise. Mean weight was maintained over this time period. There was a reduction in mean LDL and total plasma cholesterol. DISCUSSION: A healthy lifestyle programme offered through primary care that is based on a non-dieting approach may help overweight women develop and sustain positive lifestyle changes.

Comparison of abdominal damage control surgery in combat versus civilian trauma.

BACKGROUND: The majority of individuals who perform damage control surgery in the military arena are trained in civilian venues. Therefore, it is important to compare and contrast damage control performed in civilian and military settings. In contrast to civilian trauma, which is primarily caused by blunt injury and addressed at one or two surgical facilities, combat casualties primarily sustain explosion-related injuries and undergo treatment at multiple levels of care across continents. We aimed to compare patients undergoing abdominal damage control surgery across these two very different settings. METHODS: Parallel retrospective reviews were conducted over 2 years (2005-2006) in a combat setting and at a US Level I trauma center. Patients were examined during the first 7 days after injury. RESULTS: The civilian population (CP) was older (40 vs. 23; p < 0.01) with a higher injury severity score (35 vs. 27; p < 0.02). The CP experienced greater blunt injury than the military population (MP) (83 vs. 4%; p < 0.01). Explosion-related injury was only present in the MP (64%). At baseline, the CP presented with lower systolic blood pressure (108 vs. 126) and larger base deficit (9.8 vs. 6.5; p < 0.05). The MP underwent more surgeries (3.5 vs. 2.9; p = 0.02) with similar rates of fascial closure (48.7% vs. 70.0%; p = 0.11). Complication rates were similar between the CP and the MP (43% vs. 58%, respectively; p = 0.14). CONCLUSIONS: Military and civilian trauma patients who undergo damage control surgery experience similar fascial closure rates despite differing demographics and widely disparate mechanisms of injury. The MP undergoes a greater number of procedures than the CP, but complication rates do not differ between the groups.

Comparison of two school-based smoking prevention programs among South African high school students: results of a randomized trial.

BACKGROUND: Smoking rates are projected to increase substantially in developing countries such as South Africa. PURPOSE: The aim of this study was to test the efficacy of two contrasting approaches to school-based smoking prevention in South African youth compared to the standard health education program. One experimental program was based on a skills training/peer resistance model and the other on a harm minimization model. METHOD: Thirty-six public schools from two South African provinces, KwaZulu-Natal and the Western Cape, were stratified by socioeconomic status and randomized to one of three groups. Group 1 (comparison) schools (n = 12) received usual tobacco use education. Group 2 schools (n = 12) received a harm minimization curriculum in grades 8 and 9. Group 3 schools (n = 12) received a life skills training curriculum in grades 8 and 9. The primary outcome was past month use of cigarettes based on a self-reported questionnaire. RESULT: Five thousand two hundred sixty-six students completed the baseline survey. Of these, 4,684 (89%) completed at least one follow-up assessment. The net change in 30-day smoking from baseline to 2-year follow-up in the control group was 6% compared to 3% in both harm minimization (HM) and life skills training (LST) schools. These differences were not statistically significant. Intervention response was significantly moderated by both gender and race. The HM intervention was more effective for males, whereas the life skills intervention was more effective for females. For black African students, the strongest effect was evident for the HM intervention, whereas the strongest intervention effect for "colored" students was evident for the LST group. CONCLUSION: The two experimental curricula both produced similar overall reductions in smoking prevalence that were not significantly different from each other or the control group. However, the impact differed by gender and race, suggesting a need to tailor tobacco and drug use prevention programs. More intensive intervention, in the classroom and beyond, may be needed to further impact smoking behavior.

Translating an adolescent smoking cessation program into policy and practice in an Australian context.

Although Australia's restrictive tobacco control policies have made it an international leader in reducing smoking prevalence, and only 7% of teens smoke weekly, cessation efforts are still needed among adolescents. Of the campaigns and programs implemented in Australia to reduce this problem among adolescents, most have provided only abstinence messages and few have been effectively evaluated and translated into policy and practice. This article describes the translation of a harm minimization cessation program for teens, the Smoking Cessation for Youth Project (SCYP), derived from an approach developed with adults. In addition, the article describes the unique sociopolitical context of Australia in which the SCYP program was developed and the significant conceptual, contextual, and methodological factors that enabled and limited this program's effective implementation and translation.

Does harm minimisation lead to greater experimentation? Results from a school smoking intervention trial.

INTRODUCTION AND AIMS: Declines in adolescent smoking prevalence have slowed recently, resulting in increased interest and literature in tobacco harm minimisation. To date, harm reduction strategies have focused largely on modifying the product and alternative (safer) mechanisms of nicotine delivery. There has been little exploration of primary harm minimisation to prevent the onset of regular smoking among young people. A major concern expressed about harm reduction interventions and young people is that they may increase experimentation among non-users. DESIGN AND METHODS: The Smoking Cessation for Youth Project was a 2-year school-based cluster randomised controlled trial conducted in 30 Western Australian schools. Results on the primary outcome showed a significant reduction in regular smoking among 4636 13-15-year-olds receiving a harm minimisaton versus standard intervention. This paper addresses the intervention effects on 2078 students who had not smoked at baseline. RESULTS: At 20-month follow-up, smoking initiation was slightly lower among intervention students than comparison students (who received a largely abstinence-based intervention), although this difference did not attain statistical significance (OR=0.86; 95% confidence interval: 0.68, 1.09). DISCUSSION AND CONCLUSIONS: This study provided limited evidence to suggest that harm minimisation is a superior approach to abstinence-based interventions for non-smokers. However, this intervention did not contribute to increased experimentation among non-smokers. Although more trials are required, these results indicate that fears of potential negative iatrogenic effects from school-based harm minimisation interventions may be unwarranted.