OBJECTIVE: The safety profile of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors when associated with chemotherapy for the treatment of patients with extensive-stage small-cell lung cancer is still not fully unraveled.
METHODS: We performed a comprehensive searrch of the PubMed, Embase, and Cochrane databases for randomized controlled trials that investigated the addition of PD-1 or PD-L1 inhibitors to standard investigator choice chemotherapy. We used risk -ratios (RRs) with 95% confidence intervals (CIs) for all endpoints.
RESULTS: Six studies and 2,995 patients were included. At the baseline, the median age of the patients varied from 62 to 65 years, 311 (10.4%) had brain metastases, and 1,060 (35.4%) had liver metastases. PD-1/PD-L1 inhibitors were found to reduce fatal toxicities-related mortality (RR: 0.85; 95% CI: 0.80-0.91; p < 0.001; I2 = 49%). The intervention group had a higher incidence of decreased appetite (RR: 1.19; 95% CI: 1.02-1.40; p = 0.03; I2 = 0%), hyponatremia (RR: 1.51; 95% CI: 1.08-2.12; p = 0.02; I2 = 0%), and hypothyroidism (RR: 3.14; 95% CI: 1.10-8.95; p = 0.03; I2 = 81%) of any grade. Regarding adverse events of grade 3-4, there was no association of the addition of PD-1/PD-L1 inhibitors with an increased occurrence of any of the evaluated outcomes.
CONCLUSIONS: In this systematic review and meta-analysis, the incorporation of PD-1/PD-L1 inhibitors to chemotherapy demonstrated an excellent safety profile and to be a promising prospect for reshaping the established treatment paradigms for patients with extensive-stage small cell lung cancer.

Among several established indicators that are used to monitor the illicit drug scene, drug-related deaths and wastewater-based epidemiology (WBE) stand out for population-level coverage. In this study, we aimed to compare temporal trends with respect to amphetamine, methamphetamine and methylenedioxymethamphetamine (MDMA) revealed by these indicators and explore the differences in fatal toxicity between the stimulants. All deaths in which poisoning caused by amphetamine, methamphetamine or MDMA was either the underlying or contributing cause of death in Finland in 2012, 2014, 2016, 2018 and 2020 were included in the study. Consumption of the studied drugs was measured by WBE in the same years. There was a significant correlation between poisoning and drug consumption for all three stimulants, and for amphetamine and MDMA, these figures increased over the study period. The highest fatal toxicity, as expressed by the number of deaths per million doses, was obtained for methamphetamine at an estimated dose of 50 mg, followed by MDMA (100 mg dose) and with amphetamine (50 mg dose). The fatal toxicity found here for the stimulants was close to that previously reported for many prescription opioids and tricyclic antidepressants. Our study is the first to quantitatively investigate the fatal toxicity of amphetamine-type stimulants by comparing deaths with consumption estimates derived from WBE. It shows that amphetamine, methamphetamine and MDMA possess a quite similar capacity to cause death. This new approach adds to the earlier methods of estimating drug-related harm.

Oral methadone may be prescribed to detainees with the aim of minimising the risk of fatal opioid poisoning on release. To study the circumstances under which methadone-related deaths can occur in detention, we audited reports of 17 [14 male, 3 female; median (range) age 34 (22-52) years] such deaths, July 2010-December 2011. The median (range) methadone dose was 40 (10-110) mg/d (N = 16). The median (range) post-mortem blood methadone concentration was 0.42 (0.16-1.40) mg/L. Those who died within 7 days of the commencement of methadone treatment were significantly younger (Mann-Whitney U 102.5, p < 0.05), were prescribed a significantly lower dose (U = 80.0, p < 0.05) and had significantly lower blood methadone concentrations at death (U = 106.5, p < 0.02) than in those given methadone long-term. In 8 reports the prisoner had been recorded as either \'sleepy\' (N = 7), or \'unwell\' in the hours before death. In 13 deaths, the prisoner was either found dead first thing in the morning, or in one instance could not be roused (\'snoring heavily\'). Pneumonia, tracheobronchitis, end-stage cirrhosis, and ischaemic heart disease/coronary artery atherosclerosis were cited as associated factors in four patients, all of whom were on long term stable methadone treatment. Attention to warning signs of likely methadone toxicity (daytime or excessive drowsiness, snoring, nausea/vomiting) and associated risk factors (use of drugs such as benzodiazepines and gabapentinoids, the presence of respiratory infection, liver or renal disease) could help minimise the risk of unexpected death in patients given methadone.

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.
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.
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).
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.

Cleistanthus collinus is an extremely toxic plant poison. We report a case of suicidal ingestion of boiled water decoction of C. collinus where the patient presented with abdominal pain and giddiness. There was persistent metabolic acidosis and fluctuation in the level of serum potassium. The ECG changes indicated a probable myocardial injury with conduction abnormality. At autopsy, the viscera were found to be congested. The toxins were detected in the viscera and blood by TLC and HPLC. Cleistanthin A and B, collinusin, and diphyllin are the principal toxic constituents of the plant. Consumption of a boiled decoction of leaves is highly toxic and, medical management of patients is mainly supportive because the molecular mechanisms of toxin action are unknown. In the recent years, C. collinus has created a considerable amount of interest because of its complex metabolites and their cytotoxic activities. Through this study, the authors have tried to highlight different properties pertaining to C. collinus.