Medicine utilization studies in Australian individual-level dispensing data: A blinded, multi-center replicated analysis.

PURPOSE: Medicine dispensing data require extensive preparation when used for research and decisions during this process may lead to results that do not replicate between independent studies. We conducted an experiment to examine the impact of these decisions on results of a study measuring discontinuation, intensification, and switching in a cohort of patients initiating metformin. METHODS: Four Australian sites independently developed a HARmonized Protocol template to Enhance Reproducibility (HARPER) protocol and executed their analyses using the Australian Pharmaceutical Benefits Scheme 10% sample dataset. Each site calculated cohort size and demographics and measured treatment events including discontinuation, switch to another diabetes medicine, and intensification (addition of another diabetes medicine). Time to event and hazard ratios for associations between cohort characteristics and each event were also calculated. Concordance was assessed by measuring deviations from the calculated median of each value across the sites. RESULTS: Good agreement was found across sites for the number of initiators (median: 53 127, range: 51 848-55 273), gender (56.9% female, range: 56.8%-57.1%) and age group. Each site employed different methods for estimating days supply and used different operational definitions for the treatment events. Consequently, poor agreement was found for incidence of discontinuation (median 55%, range: 34%-67%), switching (median 3.5%, range: 1%-7%), intensification (median 8%, range: 5%-12%), time to event estimates and hazard ratios. CONCLUSIONS: Differences in analytical decisions when deriving exposure from dispensing data affect replicability. Detailed analytical protocols, such as HARPER, are critical for transparency of operational definitions and interpretations of key study parameters.

On- and off-label utilisation of antipsychotics in Australia (2000-2021): Retrospective analysis of two medication datasets.

OBJECTIVE: To determine antipsychotic utilisation patterns in Australian adults from 2005 to 2021, with a focus on on-label and off-label prescriptions. METHODS: We examined antipsychotic dispensing trends in adults from 2005 to 2021 using a 10% sample of the Pharmaceutical Benefits Scheme (PBS) dataset, which contains patient-level information on medicines dispensed throughout Australia. The lack of diagnostic information in PBS was substituted by analysing BEACH (Bettering the Evaluation And Care of Health) dataset, a cross-sectional national survey from 2000 to 2016, consisting of data from general practitioner-patient encounters. RESULTS: There were 5.6 million dispensings for 164,993 patients in PBS throughout this period; 69% patients had >1 dispensing, with a median of 6 per patient. Calculating the estimated period of exposure gave a total of 693,562 treatment episodes, with a median duration of 80 days. There were steady increases in both the incidence and prevalence of antipsychotic dispensings, mainly due to oral second-generation antipsychotics. The most commonly prescribed antipsychotics were quetiapine, olanzapine and risperidone, with a significant portion of patients receiving low-dose quetiapine without dose titration. Analysis of diagnostic indications from BEACH indicated that 27% of antipsychotic prescriptions were off-label for indications such as depression, dementia, anxiety and insomnia, at much lower prescribed daily dosages. CONCLUSION: The increasing prescribing and off-label use highlights concerns about chronic adverse effects caused by antipsychotics. The combined analysis of medication dispensings and the diagnostic indications for which they are prescribed is a novel approach and throws a spotlight on the need for additional monitoring of antipsychotics.

Intergenerational live-in student programmes for meaningful engagement: Creating cohesive and supportive collectives in aged-care facilities.

BACKGROUND AND OBJECTIVES: Older adults in residential aged-care facilities (RACFs) experience segregation from society and face limited opportunities to meaningfully engage on a social and/or occupational level due to various structural and systemic challenges. An occupational therapy-coordinated intergenerational live-in student programme (ILiSP) with allied health students was successfully pioneered across Sydney (Australia) to facilitate ongoing intergenerational contact. We explored how ongoing intergenerational contact influenced meaningful engagement of older adults in RACFs by investigating routinely collected clinical data and exploring stakeholders' perspectives. RESEARCH DESIGN AND METHODS: We employed a concurrent nested mixed-methods design. Residents' attendance in weekly organisational activities and students' monthly volunteer hour reports were analysed to produce statistics for demonstrating the changes in residents' activity attendance alongside ongoing intergenerational contact. Qualitative data from discussions directed by the nominal group technique (NGT) with staff, management and students, individual interviews with relatives and residents, and narrative clinical documentation were thematically analysed. RESULTS: The Wilcoxon signed-rank test indicated that residents' activity attendance increased during intergenerational contact. Qualitative data yielded three main themes-interdependence, meaningful engagement, and kinship-all associated with intergenerational contact as part of established ongoing relationships. The NGT highlighted consensus on on-site living for maintaining a cohesive and supportive collective. CONCLUSION: Despite structural and systemic challenges within RACFs that dissuade community integration, ILiSP created opportunities for students to connect/reconnect residents to new/established networks and to support residents to maintain or re-engage with previous lifestyle preferences. Therefore, ongoing intergenerational contact fostered a cohesive collective in support of the social and occupational needs of residents, which should be capitalised on by policymakers (e.g., the National Aged Care Mandatory Quality Indicator Program) and interested organisations.

Just 'nanging' around - harmful nitrous oxide use: a retrospective case series and review of Internet searches, social media posts and the coroner's database.

BACKGROUND: The chronic recreational inhalation of nitrous oxide (N2 O) 'nanging', can have adverse neurological and psychiatric effects. AIM: To evaluate cases of chronic N2 O use presenting to two hospitals, as well as to evaluate nationally N2 O deaths reported to the coroner and trends in Internet searches and social media posts related to N2 O. METHODS: Retrospective review of two toxicology units, from July 2017 to October 2020, of patients presenting with chronic N2 O use and neurological and/or psychiatric symptoms. We evaluated 10 years (2010-2019) of Internet search and social media trends involving N2 O and the National Coronial Information System (NCIS) database for deaths across Australia. RESULTS: Twenty-two patients were identified: median age 22 years, half female, 17 Asian background and 15 students. Presentations included decreased mobility or unsteady gait (n = 15) and psychiatric symptoms (n = 5). The median reported bulb use/day was 300 (interquartile range (IQR): 200-370), for a median of 6 months (IQR: 3-24). On magnetic resonance imaging, 10/18 had subacute combined degeneration of the spinal cord and 7/7 sensorimotor neuropathy on nerve conduction studies. All received high-dose intramuscular vitamin B12 and 11 methionine. Despite prolonged rehabilitation, nine required walking aids on discharge. Since 2017, social media posts and Internet searches for N2 O increased rapidly, the latter mostly directed at obtaining N2 O canisters. From the NCIS, 36 deaths were identified, 12 unintentional (recreational drug use), 20 intentional self-harm and 4 traumatic. CONCLUSION: We report a case series of symptomatic chronic N2 O use, many with ongoing neurological sequelae. Furthermore, a sharp increase in Internet searches to obtain N2 O cannisters was noted. Education of high-risk student groups on the long-term sequelae is important.

Machine read frontal QRS-T angle and QTc is no substitute for manual measurement of QTc in pro-arrhythmic drug overdose.

INTRODUCTION: To investigate whether there is an association between the blocking of cardiac potassium channels, which is characterised by a prolonged QTc interval and the frontal QRS-T angle after overdose by QT prolonging drugs. METHODS: We obtained patient medical records associated with QT prolonging drugs from 3 different hospitals: the Calvary Mater Newcastle Hospital (CMNH), Royal Prince Alfred Hospital (RPAH) and Prince of Wales Hospital (POWH). RPAH and POWH admissions were taken between 4/01/2017 to 1/11/2019, and CMNH admissions were taken between 4/01/2013 to 24/06/2018. Demographic information and details of overdose were collected. All admission ECGs were manually measured. Linear regression was used to assess the relationship between various QTc formulas and the frontal QRS-T angle. A Bland-Altman plot was used to examine agreement between manual and machine QT intervals. RESULTS: 144 patients met the inclusion criteria for analysis. None of the patients developed torsades de pointes (TdP). There was no linear association between the QRS-T angle and the various QTc formulas (For QRS-T angle: QTcRTH: p = 0.76, QTcB: p = 0.83, QTcFri: p = 0.90, QTcFra: p = 0.13, QTcH: p = 0.97; For square root transformation of the QRS-T angle: QTcRTH: p = 0.18, QTcB: p = 0.33, QTcFri: p = 0.95, QTcFra: p = 0.47, QTcH: p = 0.33). Agreement between machine and manual QT measurements was low. CONCLUSIONS: The frontal QRS-T angle cannot substitute the QTc in assessing the blockage of cardiac potassium channels in drug induced long QT syndrome. We also support the consensus that despite the availability of machine measurements of the QT interval, manual measurements should also be performed.

Circulating human microRNA biomarkers of oxalic acid-induced acute kidney injury.

Oxalic acid-induced nephrotoxicity and acute kidney injury result from formation of calcium oxalate crystals. Oxalic acid-induced acute kidney injury is a significant problem in many parts of the world. Circulating biomarkers that can accurately and reproducibly detect acute kidney injury are highly desirable. We used a high sensitivity discovery platform to identify signature microRNAs to distinguish healthy individuals never exposed to oxalic acid (n = 4) from those who were exposed to oxalic acid but had no injury (NOAKI; n = 4), moderate injury (AKIN2; n = 4) or severe injury (AKIN3; n = 4). Longitudinal analyses identified 4-8 h post-ingestion as the best time to detect AKIN2/3. We validated a signature of 53 microRNAs identified in the discovery, in a second cohort of individuals exposed to oxalic acid (NOAKI = 11, AKIN2 = 8 and AKIN3 = 18) and healthy controls (n = 19). Thirteen microRNAs were significantly downregulated in acute kidney injury patients compared to NOAKI within 8-h post-ingestion. Five microRNAs (miR-20a, miR-92a, miR-93, miR-195, miR-451) had a highly significant correlation with normalized urinary albumin, serum creatinine at 24 h and creatinine clearance. Logistic regression of these microRNAs had AUC-ROC of 0.85 predicting AKIN2/3 and discriminated patients from healthy controls (AUC-ROC = 0.93). mRNA targets of these microRNAs identified oxidative stress pathways of nephrotoxicity in proximal tubule and glomeruli nephrotoxicity. In conclusion, the downregulation of multiple circulating microRNAs in patients correlated with the severity of oxalic acid-induced acute kidney injury. A set of microRNAs (miR-20a, miR-92a, miR-93, miR-195, miR-451) could be promising biomarkers for early detection of oxalic acid-induced acute kidney injury.

The relative lethal toxicity of pharmaceutical and illicit substances: A 16-year study of the Greater Newcastle Hunter Area, Australia.

AIMS: We aim to calculate 2 metrics of relative lethal toxicity; the fatal toxicity index (FTI; number of deaths per year of a daily dose) and the case fatality (CF; number of deaths per overdose) with a focus on opioids, antidepressants, antipsychotics, benzodiazepines and illicit drugs. METHODS: This descriptive cohort study used the Australian National Coronial Information System (NCIS) to identify a population of individuals with drug-associated deaths in the Greater Newcastle Hunter Area between January 2002 and December 2016. This was combined with Australian medicine dispensing data and corresponding data from the Hunter Area Toxicology Service to calculate FTI and CF. RESULTS: There were 444 drug-related deaths and 21,296 overdoses during the study period. FTI and CF were well correlated (Spearman's rho 0.64, P < .001). Of the classes of interest, opioids had the highest FTI (40.3 95% confidence interval [CI] 35.2-45.4 deaths per 100 years of use at the defined daily dose or deaths/DDD/100 years) and CF (12.4% 95%CI 11.0-13.9). Fentanyl, methadone and morphine had the highest relative fatal toxicity within this class. Tricyclic antidepressants had the highest relative fatal toxicity of all antidepressants (FTI 14.5 95%CI 9.7-19.3 deaths/DDD/100 years and CF 7.1% [95%CI 4.8-9.3]) and benzodiazepines appeared to be more associated with multiple agent deaths than single. Of the illicit drugs, heroin had the highest CF (26.4%, 95%CI 19.1-33.7). CONCLUSION: Knowledge of relative lethal toxicity is useful to prescribers and medicines and public health policy makers in restricting access to more toxic drugs and may also assist coroners in determining cause of death.

Does forgiveness mediate the impact of school bullying on adolescent mental health?

OBJECTIVE: The link between both bullying and victimisation and psychopathology has been well established. Forgiveness has been associated with better mental health. However, few studies have examined the relationship between adolescent forgiveness, psychopathology and bullying/victimisation. This study investigated forgiveness as a mediator of the adverse mental health problems experienced by bullies and victims of bullying. METHOD: Participants were 355 Year 10 or Year 11 pupils (age = 14.9 years) from two British secondary schools in 2007, who completed self-administered measures on bullying and victimisation, mental health, forgiveness of self and others, and forgivingness. The mediating influence of forgiveness on the impact of bullying/victimisation on mental health was tested with a structural equation model. RESULTS: Data from 55.6% of the 639 eligible pupils were analysed. Results confirmed an association between bullying/victimisation, forgiveness and psychopathology. Forgiveness scores were found to play a mediating role between bullying/victimisation and psychopathology. CONCLUSIONS: Victimised adolescents who were better able to forgive themselves were more likely to report lower levels of psychopathology, while bullying adolescents who were unable to forgive others were more likely to report higher levels of psychopathology. This suggests a greater role for forgiveness within future research, intervention and policy on bullying. Forgiveness can form a valuable part of preventative and educational anti-bullying programmes.

The long-term effects of training interventions on transfusion practice: a follow-up audit of red cell concentrate utilisation at Kimberley Hospital, South Africa.

This audit in chronically anaemic adult patients assesses whether red cell concentrate is transfused according to guidelines, and evaluates the impact of training interventions, compared with a similar audit conducted in 2010. Retrospectively, 25 transfusion episodes were audited for appropriateness, the investigation of anaemia, threshold achievement, wastage, and informed consent. After training interventions, a further 25 episodes were prospectively analysed. The effects of current training interventions were not shown to have a statistically significant impact. Compared to a 2010 audit, however, a statistically significant improvement was demonstrated in transfusion practice, suggesting that training interventions may lead to sustainable long-term improvements.

Online health information behaviour and its association with statin adherence in patients with high cardiovascular risk: A prospective cohort study.

Objective: Statins are effective for preventing cardiovascular disease. However, many patients decide not to take statins because of negative influences, such as online misinformation. Online health information may affect decisions on medication adherence, but measuring it is challenging. This study aimed to examine the associations between online health information behaviour and statin adherence in patients with high cardiovascular risk. Methods: A prospective cohort study involving 233 patients with high cardiovascular risk was conducted at a primary care clinic in Malaysia. Participants used a digital information diary tool to record online health information they encountered for 2 months and completed a questionnaire about statin necessity, concerns and adherence at the end of the observation period. Data were analysed using structural equation modelling. Results: The results showed that 55.8% (130 of 233 patients) encountered online health information. Patients who actively sought online health information (91 of 233 patients) had higher concerns about statin use (ß = 0.323, p = 0.023). Participants with higher concern about statin use were also more likely to be non-adherent (ß = -0.337, p < 0.001). Patients who actively sought online health information were more likely to have lower statin adherence, mediated by higher concerns about statin use (indirect effect, ß = -0.109, p = 0.048). Conclusions: Our results suggest that patients with higher levels of concern about statins may be actively seeking online information about statins, and their concerns might influence how they search, what they find, and the potential to encounter misinformation. Our study highlights the importance of addressing patients' concerns about medications to improve adherence.

The implementation of a real time early warning system using machine learning in an Australian hospital to improve patient outcomes.

BACKGROUND: Early Warning Scores (EWS) monitor inpatient deterioration predominantly using vital signs. We evaluated inpatient outcomes after implementing an Artificial Intelligence (AI) based intervention in our local EWS. METHODS: A prior study calculated a Deterioration Index (DI) with logistic regression utilising demographics, vital signs, and laboratory results at multiple time points to predict any major adverse event (MAE-all cause mortality, ICU admission, or medical emergency team activation). The current study is a single hospital, pre-post study in Australia comparing the DI plus the existing EWS (Between the Flags-BTF) to only BTF. Data were collected on all eligible inpatients (≥16 years, admitted ≥24 hours, in general non-palliative wards). Controls were inpatients in the same hospital between January and December 2019. The DI was integrated into the electronic medical record and alerts were sent to senior ward nurse phones (July 2020-April 2021). RESULTS: We enrolled 28,639 patients (median age 73 years, IQR: 60-83) with 52.3% female. The intervention and control groups did not show any statistically significant differences apart from reduced admissions via the emergency department in the intervention group (40.4% vs 41.6%, P = 0.03). Risk for an MAE was lower in intervention than control (RR: 0.81; 95%CI: 0.74-0.89). Length of hospital stay was significantly reduced in the intervention group (3.74 days, IQR 1.84-7.26) compared to the control group (3.86 days, IQR 1.86-7.86, P = 0.002) CONCLUSIONS: Implementing the DI in one hospital in Australia was associated with some improved patient outcomes. Future RCTs are needed for further validation.

Effect of receiving mobile text messages on cortisol concentrations in students at the University of the Free State.

Background: Texting has become central to social life, with adverse effects on physiological functioning. Research into the impact of texting on cortisol secretion is limited. Aim: Thus study aimed to determine how receiving mobile text messages affected salivary cortisol concentrations and investigate the moderating effects of stress, anxiety and depression on cortisol secretion. Setting: Undergraduate physiology students attending physiology lectures at the Faculty of Health Sciences, University of the Free State, 2016. Methods: An experimental, crossover, quantitative design was used. Participants were involved over two consecutive days, receiving mobile text messages (intervention) on one day and acting as their own control on the other. Self-reported data on stress, anxiety, depression and subjective experience of the study, and saliva samples were collected. Text frequency and wording (neutral, positive, negative) were varied among participants. Results: Forty-eight students participated in the study. Salivary cortisol concentrations did not differ significantly between the intervention and control days. High anxiety levels were associated with increased cortisol concentrations. No associations with cortisol concentrations were documented in low to moderate anxiety, stress, depression or how participants experienced the intervention. There were no significant differences between text frequency, text emotion and change in cortisol concentrations on the intervention day. Conclusion: Receiving mobile text messages did not elicit a significant cortisol response in participants. Contribution: Findings added to the body of knowledge about the effect of texting on student learning by measuring salivary cortisol concentrations in a lecture setting, with investigation into the moderating effects of stress, anxiety, depression and participants' subjective experience.

Five healthcare trajectories in the year before suicide and what they tell us about opportunities for prevention: a population-level case series study.

Background: Suicide prevention requires a shift from relying on an at-risk individual to engage with the healthcare system. Understanding patterns of healthcare engagement by people who have died by suicide may provide alternative directions for suicide prevention. Methods: This is a population-based case-series study of all suicide decedents (n = 3895) in New South Wales (NSW), Australia (2013-2019), with linked coronial, health services and medicine dispensing data. Healthcare trajectories were identified using a k-means longitudinal 3d analysis, based on the number and type of healthcare contacts in the year before death. Characteristics of each trajectory were described. Findings: Five trajectories of healthcare utilisation were identified: (A) none or low (n = 2598, 66.7%), (B) moderate, predominantly for physical health (n = 601, 15.4%), (C) moderate, with high mental health medicine use (n = 397, 10.2%), (D) high, predominantly for physical health (n = 206, 5.3%) and E) high, predominantly for mental health (n = 93, 2.4%). Given that most decedents belonged to Trajectory A this suggests a great need for suicide preventive interventions delivered in the community, workplace, schools or online. Trajectories B and D might benefit from opioid dispensing limits and access to psychological pain management. Trajectory C had high mental health medicine use, indicating that the time that medicines are prescribed or dispensed are important touchpoints. Trajectory E had high mental health service predominantly delivered by psychiatrists and community mental health, but limited psychologist use. Interpretation: Although most suicide decedents made at least one healthcare contact in the year before death, contact frequency was overall very low. Given the characteristics of this group, useful access points for such intervention could be delivered through schools and workplaces, with a focus on alcohol and drug intervention alongide suicide awareness. Funding: Australia's National Health and Medical Research Council.

Has there been an increase in nitrous oxide use and associated harms in Australia? An analysis of triangulated data sources, 2003-2020.

BACKGROUND: There is growing concern, globally, regarding use of nitrous oxide (N2O) for intoxication purposes. This paper aims to examine trends in: (i) past six month N2O use among a sample of people who use regularly use ecstasy and/or other illicit stimulants (2003-2020); (ii) volume of N2O-related Google searches and social media posts (2009-2020); and (iii) N2O-related calls to Poisons Information Centres (PIC) (2004-2020). METHODS: Data were obtained from annual interviews with sentinel samples of Australians aged ≥16 years who used ecstasy and/or other illicit stimulants ≥monthly and resided in a capital city (∼800 each year); Google search activity; social media posts; and exposure calls to four PIC. RESULTS: Among samples of people who regularly use ecstasy and/or other illicit stimulants, past six-month N2O use increased 10% each year from 2009 to 2020, with the sharpest increase observed between 2015 and 2018 (25.4% p/year; 95% CI: 14.6-37.1). Frequency and quantity of N2O use remained stable and low. Google search probabilities increased by 1.8% each month from January 2009 and December 2019 (95% CI: 1.5-2.2), with the sharpest increase observed between July 2016 to December 2017 (6.0% p/month; 95% CI: 4.4-7.5). Social media posts increased 2.0% per month from January 2009 and December 2019 (95% CI: 1.1-3.0), with the sharpest increase observed between March and October 2017 (19.2% p/month; 95% CI: 1.7-39.7). The number of N2O-related calls to Australian PIC increased sixfold between 2016 (16) and 2020 (111). CONCLUSIONS: Triangulation of various data sources indicate significant shifts in N2O use and harms in Australia. This includes increases in use, Google searches and social media posts, although these have plateaued in recent years, coupled with increased rates of harm. These findings correspond with evidence of a global increase in N2O use and harm, highlighting the need for education of both people who use N2O and health professionals.

Community-based alcohol education intervention (THEATRE) study to reduce harmful effects of alcohol in rural Sri Lanka: design and adaptation of a mixed-methods stepped wedge cluster randomised control trial.

INTRODUCTION: Alcohol consumption is a leading cause of mortality, morbidity and adverse social sequelae in Sri Lanka. Effective community-based, culturally adapted or context-specific interventions are required to minimise these harms. We designed a mixed-methods stepped wedge cluster randomised control trial of a complex alcohol intervention. This paper describes the initial trial protocol and subsequent modifications following COVID-19. METHODS AND ANALYSIS: We aimed to recruit 20 villages (approximately n=4000) in rural Sri Lanka. The proposed intervention consisted of health screening clinics, alcohol brief intervention, participatory drama, film, and public health promotion materials to be delivered over 12 weeks.Following disruptions to the trial resulting from the Easter bombings in 2019, COVID-19 and a national financial crisis, we adapted the study in two main ways. First, the interventions were reconfigured for hybrid delivery. Second, a rolling pre-post study evaluating changes in alcohol use, mental health, social capital and financial stress as the primary outcome and implementation and ex-ante economic analysis as secondary outcomes. ETHICS AND DISSEMINATION: The original study and amendments have been reviewed and granted ethical approval by Rajarata University of Sri Lanka (ERC/2018/21-July 2018 and February 2022) and the University of Sydney (2019/006). Findings will be disseminated locally in collaboration with the community and stakeholders.The new hybrid approach may be more adaptable, scalable and generalisable than the planned intervention. The changes will allow a closer assessment of individual interventions while enabling the evaluation of this discontinuous event through a naturalistic trial design. This may assist other researchers facing similar disruptions to community-based studies. TRIAL REGISTRATION: The trial is registered with the Sri Lanka Clinical Trials Registry; https://slctr.lk/trials/slctr-2018-037.

Role of age-sex as underlying risk factors for death in acute pesticide self-poisoning: a prospective cohort study.

BACKGROUND: There is growing evidence in the literature that patients' age is associated with increased risk of death in acute pesticide poisoning. However, few studies have investigated whether the age effect differs between males and females. We aimed to examine the association between age-sex and risk of death in acute pesticide self-poisoning. METHODS: A prospective cohort of deliberate pesticide-poisoned patients admitted to ten rural Sri Lankan hospitals between March 2002 and December 2019. The pesticide ingested was identified based on identification of container or history. A mixed effects logistic regression was fitted to investigate the effect of age-sex on death in acute pesticide self-poisoning adjusting for clinical symptoms on admission, measured by Glasgow Coma Scale and Poison Severity Score, and controlling for clustering among hospital sites. RESULTS: In total, 201 different pesticides were ingested by patients. 6,643 patients ingested an unknown pesticide. A single pesticide was co-ingested with alcohol by 4,603 patients. Of the 28,303 patients enrolled, 2,028 patients died, resulting in case fatality of 7.2% (95% CI 6.9-7.5). The effect of age on case fatality was stronger for males after 21 years of age. The odds of dying for each 5 years increase in age was 1.26 (95% CI 1.23-1.28) times higher for males versus 1.14 (95% CI 1.10-1.19) times higher for females. Missing data were handled by multiple imputation. CONCLUSION: Patient's age-sex are important risk factors for death in acute pesticide self-poisoning even after controlling for clinical effects. The age effect on the odds of dying was significantly different for males and females, with this effect being stronger for males. Given that patient's age and sex are very easy to collect on admission, our study highlights the need for incorporating these risk factors in policy and clinical decisions.

When are alcohol-related blackout Tweets written in the United States?

BACKGROUND: Alcohol use varies throughout the year and often peaks on weekends or during celebrations (e.g., New Year's). There is not a perfect correlation between alcohol use and negative consequences, and the extent to which one particularly risky consequence-an alcohol-related blackout-is more common during certain times of the year is unknown. Identifying when blackouts occur may help identify which periods are associated with more risk and be critical in designing public health campaigns. Thus, we examined Twitter data to ascertain whether alcohol-related blackouts occur more during certain holidays/celebrations than typical weekends and whether they differed in timing from general alcohol-related Tweets. METHODS: We used a Twitter-sponsored platform to access unique Tweets written in the United States referencing blackouts (e.g., "blackout") and alcohol generally (e.g., "drunk"). RESULTS: The final dataset included 3.5 million blackout Tweets and 591 million alcohol Tweets (written between 2009 and 2020). Both blackout and alcohol Tweets were written in the late evening, on weekends, and during certain holidays (New Years, St. Patrick's). However, relative to typical weekends, only blackout Tweets were more common during Thanksgiving and only general alcohol-related Tweets were more common during Cinco de Mayo. CONCLUSION: While blackout and alcohol-related Tweets were similar in time of day (peaking in the evening) and day of week (peaking on weekends), they differed during certain celebrations/holidays, suggesting that while alcohol use may be more common during some celebrations, others are more associated with serious harms.

Acute fungicide self-poisoning - a prospective case series.

BACKGROUND: Pesticide self-poisoning is a global clinical and public health problem. While self-poisoning with insecticides and herbicides has been extensively studied, there is minimal literature on acute fungicide self-poisoning. We aimed to study the clinical course and outcome of fungicide self-poisoned patients recruited to a prospective cohort in Sri Lanka. METHODS: We conducted a prospective study of patients presenting with fungicide self-poisoning to nine hospitals in Sri Lanka between 2002 and 2020. Patients were enrolled by clinical research assistants, with clinical outcomes being recorded at regular review for each patient. RESULTS: We identified 337 cases of self-poisoning with fungicides (alcohol as only co-ingestant), including 28 different fungicides across 5 different fungicide classes. Median time from ingestion to examination was 3.1 (1.8-5.7) h. Nearly all presented to hospital fully conscious (GCS 15, 15-15)- only 27 patients (8.0%) presented with reduced GCS (<15) and only 2 (0.6%) had GCS 3/15. Most patients (333/337, 98.8%) made a full recovery, of whom only eight (2.37%) required intubation and ventilation. Four patients died (case fatality rate: 1.2%; 95% CI 0.0-23.4) after ingestion of edifenphos (n = 2), propamocarb and pyraclostrobin. CONCLUSION: Fungicide self-poisoning appears to be less hazardous than insecticide or herbicide self-poisoning, with a substantially lower case fatality in the same cohort. Edifenphos is an exception to this 'less toxic' rule; as a WHO Class Ib highly hazardous pesticide, we recommend its withdrawal from, and replacement in, global agricultural practice. Propamocarb should be listed in the WHO hazard classification as propamocarb hydrochloride to reflect the higher toxicity of the common agricultural formulation. Pyraclostrobin currently has no WHO classification; one is urgently required now that its ingestion has now been linked the death of a patient. Additional prospective clinical data on fungicide self-poisoning is required to expand knowledge on the effects of these diverse compounds.