Combinations of QT-prolonging drugs: towards disentangling pharmacokinetic and pharmaco-dynamic effects in their potentially additive nature.

Background: Whether arrhythmia risks will increase if drugs with electrocardiographic (ECG) QT-prolonging properties are combined is generally supposed but not well studied. Based on available evidence, the Arizona Center for Education and Research on Therapeutics (AZCERT) classification defines the risk of QT prolongation for exposure to single drugs. We aimed to investigate how combining AZCERT drug categories impacts QT duration and how relative drug exposure affects the extent of pharmacodynamic drug–drug interactions. Methods: In a cohort of 2558 psychiatric inpatients and outpatients, we modeled whether AZCERT class and number of coprescribed QT-prolonging drugs correlates with observed rate-corrected QT duration (QTc) while also considering age, sex, inpatient status, and other QTc-prolonging risk factors. We concurrently considered administered drug doses and pharmacokinetic interactions modulating drug clearance to calculate individual weights of relative exposure with AZCERT drugs. Because QTc duration is concentration-dependent, we estimated individual drug exposure with these drugs and included this information as weights in weighted regression analyses. Results: Drugs attributing a ‘known’ risk for clinical consequences were associated with the largest QTc prolongations. However, the presence of at least two versus one QTc-prolonging drug yielded nonsignificant prolongations [exposure-weighted parameter estimates with 95% confidence intervals for ‘known’ risk drugs + 0.93 ms (–8.88;10.75)]. Estimates for the ‘conditional’ risk class increased upon refinement with relative drug exposure and coadministration of a ‘known’ risk drug as a further risk factor. Conclusions: These observations indicate that indiscriminate combinations of QTc-prolonging drugs do not necessarily result in additive QTc prolongation and suggest that QT prolongation caused by drug combinations strongly depends on the nature of the combination partners and individual drug exposure. Concurrently, it stresses the value of the AZCERT classification also for the risk prediction of combination therapies with QT-prolonging drugs

Mega El Niño's change the playing field for culturally important tree species and hence the foundation for human-nature interactions in tropical forests

Humans have interacted with trees for millennia and the strength of such interactions determines the long-term social values of trees and forests. Such ecocultural linkages could be important to promote during reforestation efforts, potentially helping to turn the tide on the current rapid extinction of cultural and biological diversity. In addition, predicting the fate of ecoculturally important species to changing climates may help guide tree species selection best-suited to future climates. We assessed the vulnerability of four ecoculturally important tree species native to Southeast Asia to an extreme drought: Koompassia excelsa, Nephelium lappaceum, Shorea fallax and Shorea leprosula. These species provide distinct and unique products, and Koompassia excelsa is well-represented in local mythological stories and considered a Cultural Keystone Species (CKS). We used two complementary approaches: 1) an experimental common garden and 2) naturally occurring wild trees growing in a secondary forest and compared the performance of trees before, after, and during the 2016 El Niño event with record breaking low precipitation and high temperatures. We found that mortality of the CKS K. excelsa in the common garden, along with mortality and growth of wild trees were unaffected by the El Niño drought. In contrast, young trees of N. lappaceum and S. fallax planted in the common garden had mortality 4 and 3 times higher, respectively, during the El Niño drought compared to normal years. Growth rate of S. fallax in the wild was also significantly lower during the El Niño drought and this effect was particularly pronounced in highly disturbed forests. Our results demonstrate that the impact of extreme climatic events, that are predicted to become more common with climate change, on culturally important tree species is species specific. Management of such species may thus need species specific measures to maintain viable populations and hence provide the basic physical settings for human-nature interactions and associated cultural identities to persist. In this context, our findings that cultural keystone species such as K. excelsa could be drought tolerant is noteworthy, as investing on such species could prove to be beneficial for both local cultures and conservation of native ecosystems and biodiversity

The road to recovery: a synthesis of outcomes from ecosystem restoration in tropical and sub-tropical Asian forests

Current policy is driving renewed impetus to restore forests to return ecological function, protect species, sequester carbon and secure livelihoods. Here we assess the contribution of tree planting to ecosystem restoration in tropical and sub-tropical Asia; we synthesize evidence on mortality and growth of planted trees at 176 sites and assess structural and biodiversity recovery of co-located actively restored and naturally regenerating forest plots. Mean mortality of planted trees was 18% 1 year after planting, increasing to 44% after 5 years. Mortality varied strongly by site and was typically ca 20% higher in open areas than degraded forest, with height at planting positively affecting survival. Size-standardized growth rates were negatively related to species-level wood density in degraded forest and plantations enrichment settings. Based on community-level data from 11 landscapes, active restoration resulted in faster accumulation of tree basal area and structural properties were closer to old-growth reference sites, relative to natural regeneration, but tree species richness did not differ. High variability in outcomes across sites indicates that planting for restoration is potentially rewarding but risky and context-dependent. Restoration projects must prepare for and manage commonly occurring challenges and align with efforts to protect and reconnect remaining forest areas

Survival and heights of trees planted for forest restoration in South and Southeast Asia

This dataset consists of survival and heights of trees planted for forest restoration in South and Southeast Asia and the associated analytical code. The data consists of tree censuses collated from published studies, grey literature and data provided by co-authors, up to/including May 2021. Data are collated from 176 sites in areas where disturbance or clearance of the natural forest had occurred and where trees were then planted and monitored over time. The analyses included here model height growth, extract annual size-standardised growth rates and test the effects of biophysical and climatic conditions and planting regimes on survival and growth. This dataset was created to represent the current state of knowledge on forest restoration outcomes in South and Southeast Asia. This is the full dataset for the survival and height analysis

Plot-level forest structure, carbon density and tree species richness data from restoration sites in South and Southeast Asia

This dataset consists of structure, biomass (carbon density) and biodiversity (plant species richness) from forest inventory plots at forest restoration sites in South and Southeast Asia and the code for the analyses of these data as conducted in Banin, Raine et al (2023). The recorded data consists of plot level censuses carried out up to May 2021 collated from published studies, grey literature and data provided by co-authors. This represents the collation of data from 11 sites in areas where disturbance had led to the clearance or degradation of natural forest. Plots where tree seedlings were planted (active restoration) and plots where no seedling planting took place (natural regeneration) were censused for structure, biomass and/or biodiversity. Some of the sites in the dataset also recorded data at old growth forest plots for reference, and/or provided repeat measures of forest metrics over time. The dataset also includes the code used for analysis of this plot level data, used to compare the outcome of different restoration approaches