Making food systems safer: Time to curb use of highly hazardous pesticides

Use of synthetic chemical pesticides has expanded widely. These insecti-cides, herbicides, and fungicides have helped to boost crop production, but at a major cost – one whose full extent remains unknown. Many commonly used pesticides – especially in developing countries – are now considered “highly hazardous” by experts due to their proven or likely harms to nature and people.1 Evidence from farms in the global South confirms heavy use of pesticides, including substances banned elsewhere. Farmers and nearby communities face the most direct health threats. This policy brief outlines key harms and research findings, high-lights alternatives to pesticide-intensive agricultural practices, and calls for phasing out the riskiest substances – in line with human rights and proper application of the precautionary principle

Copeptin predicts 10-year all-cause mortality in community patients: a 10-year prospective cohort study

Copeptin, the C-terminal part of the arginine vasopressin (AVP) precursor peptide, is secreted in response to stress and correlates with adverse clinical outcomes in the acute-care hospital setting. There are no comprehensive data regarding its prognostic value in the community. We evaluated associations of copeptin levels with 10-year mortality in patients visiting their general practitioner (GP) for a respiratory infection included in a previous trial.; This is a post hoc analysis including data from 359 patients included in the PARTI trial. Copeptin was measured in batch-analysis on admission and after 7 days. We calculated Cox regression models and area under the receiver operating characteristic curve (AUC) to assess an association of copeptin with mortality and adverse outcome. Follow-up data were collected by GP, patient and relative tracing through phone interviews 10 years after trial inclusion.; After a median follow-up of 10.0 years, mortality was 9.8%. Median admission copeptin levels (pmol/L) were significantly elevated in non-survivors compared to survivors (13.8, IQR 5.9-27.8; vs. 6.3 IQR 4.1-11.5; p>0.001). Admission copeptin levels were associated with 10-year all-cause mortality [age-adjusted hazard ratio 1.7 (95% CI, 1.2-2.5); p>0.001, AUC 0.68]. Results were similar for discharge copeptin levels. Copeptin also predicted adverse outcomes defined as death, pulmonary embolism and major adverse cardiac and cerebrovascular events.; In a sample of community-dwelling patients visiting their GP for a respiratory infection, copeptin levels were associated with 10-year all-cause mortality. In conjunction with traditional risk factors, this marker may help to better direct preventive measures in this population

Prospective evaluation of biomarkers for prediction of quality of life in community-acquired pneumonia

Most clinical research investigated prognostic biomarkers for their ability to predict cardiovascular events or mortality. It is unknown whether biomarkers allow prediction of quality of life (QoL) after survival of the acute event. Herein, we investigated the prognostic potential of well-established inflammatory/cardiovascular blood biomarkers including white blood cells (WBC), C-reactive protein (CRP), procalcitonin (PCT), pro-adrenomedullin (proADM) and pro-atrial natriuretic peptide (proANP) in regard to a decline in QoL in a well-defined cohort of patients with community-acquired pneumonia (CAP).; Within this secondary analysis including 753 patients with a final inpatient diagnosis of CAP from a multicenter trial, we investigated associations between admission biomarker levels and decline in QoL assessed by the EQ-5D health questionnaire from admission to day 30 and after 6 years.; Admission proADM and proANP levels significantly predicted decline of the weighted EQ-5D index after 30 days (n=753) with adjusted odds ratios (ORs) of 2.0 ([95% CI 1.1-3.8]; p=0.027) and 3.7 ([95% CI 2.2-6.0]; p>0.001). Results for 6-year outcomes (n=349) were similar with ORs of 3.3 ([95% CI 1.3-8.3]; p=0.012) and 6.2 ([95% CI 2.7-14.2]; p>0.001). The markers were associated with most of the different QoL dimensions including mobility, self-care, and usual activities, but not pain/discomfort and to a lesser degree anxiety/depression and the visual analogue scale (VAS). Initial WBC, PCT and CRP values did not well predict QoL at any time point.; ProADM and proANP accurately predict short- and long-term decline in QoL across most dimensions in CAP patients. It will be interesting to reveal underlying physiopathology in future studies

Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study

As part of the immune defense during infection, an increase in enzyme activity of indoleamine 2,3-dioxygenase (IDO) leads to a breakdown of tryptophan to kynurenine. In previous animal studies, therapeutic antagonism of IDO resulted in reduced sepsis mortality. We investigated the prognostic ability of tryptophan, serotonin, kynurenine and IDO (represented by the ratio of kynurenine/tryptophan) to predict adverse clinical outcomes in patients with community-acquired pneumonia (CAP).; We measured tryptophan, serotonin and kynurenine on admission plasma samples from CAP patients included in a previous multicenter trial by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We studied their association with inflammation (C-reactive protein), infection (procalcitonin) and clinical outcome.; Mortality in the 268 included patients was 45% within 6 years of follow-up. IDO and kynurenine showed a strong positive correlation with markers of infection (procalcitonin) and inflammation (C-reactive protein) as well as sepsis and CAP severity scores. Tryptophan showed similar, but negative correlations. In a multivariate regression analysis adjusted for age and comorbidities, higher IDO activity and lower tryptophan levels were strongly associated with short-term adverse outcome defined as death and/or ICU admission within 30 days with adjusted odds ratios of 9.1 [95% confidence interval (CI) 1.4-59.5, p=0.021] and 0.11 (95% CI 0.02-0.70, p=0.021). Multivariate analysis did not reveal significant associations for kynurenine and serotonin.; In hospitalized CAP patients, higher IDO activity and lower tryptophan levels independently predicted disease severity and short-term adverse outcome. Whether therapeutic modulation of IDO has positive effects on outcome needs further investigation

Prospective evaluation of biomarkers for prediction of quality of life in community-acquired pneumonia

AbstractBackground: Most clinical research investigated prognostic biomarkers for their ability to predict cardiovascular events or mortality. It is unknown whether biomarkers allow prediction of quality of life (QoL) after survival of the acute event. Herein, we investigated the prognostic potential of well-established inflammatory/cardiovascular blood biomarkers including white blood cells (WBC), C-reactive protein (CRP), procalcitonin (PCT), pro-adrenomedullin (proADM) and pro-atrial natriuretic peptide (proANP) in regard to a decline in QoL in a well-defined cohort of patients with community-acquired pneumonia (CAP). Methods: Within this secondary analysis including 753 patients with a final inpatient diagnosis of CAP from a multicenter trial, we investigated associations between admission biomarker levels and decline in QoL assessed by the EQ-5D health questionnaire from admission to day 30 and after 6 years. Results: Admission proADM and proANP levels significantly predicted decline of the weighted EQ-5D index after 30 days (n=753) with adjusted odds ratios (ORs) of 2.0 ([95% CI 1.1-3.8]; p=0.027) and 3.7 ([95% CI 2.2-6.0]; p<0.001). Results for 6-year outcomes (n=349) were similar with ORs of 3.3 ([95% CI 1.3-8.3]; p=0.012) and 6.2 ([95% CI 2.7-14.2]; p<0.001). The markers were associated with most of the different QoL dimensions including mobility, self-care, and usual activities, but not pain/discomfort and to a lesser degree anxiety/depression and the visual analogue scale (VAS). Initial WBC, PCT and CRP values did not well predict QoL at any time point. Conclusions: ProADM and proANP accurately predict short- and long-term decline in QoL across most dimensions in CAP patients. It will be interesting to reveal underlying physiopathology in future studies

Copeptin predicts 10-year all-cause mortality in community patients: a 10-year prospective cohort study

AbstractBackground: Copeptin, the C-terminal part of the arginine vasopressin (AVP) precursor peptide, is secreted in response to stress and correlates with adverse clinical outcomes in the acute-care hospital setting. There are no comprehensive data regarding its prognostic value in the community. We evaluated associations of copeptin levels with 10-year mortality in patients visiting their general practitioner (GP) for a respiratory infection included in a previous trial. Methods: This is a post hoc analysis including data from 359 patients included in the PARTI trial. Copeptin was measured in batch-analysis on admission and after 7 days. We calculated Cox regression models and area under the receiver operating characteristic curve (AUC) to assess an association of copeptin with mortality and adverse outcome. Follow-up data were collected by GP, patient and relative tracing through phone interviews 10 years after trial inclusion. Results: After a median follow-up of 10.0 years, mortality was 9.8%. Median admission copeptin levels (pmol/L) were significantly elevated in non-survivors compared to survivors (13.8, IQR 5.9-27.8; vs. 6.3 IQR 4.1-11.5; p<0.001). Admission copeptin levels were associated with 10-year all-cause mortality [age-adjusted hazard ratio 1.7 (95% CI, 1.2-2.5); p<0.001, AUC 0.68]. Results were similar for discharge copeptin levels. Copeptin also predicted adverse outcomes defined as death, pulmonary embolism and major adverse cardiac and cerebrovascular events. Conclusions: In a sample of community-dwelling patients visiting their GP for a respiratory infection, copeptin levels were associated with 10-year all-cause mortality. In conjunction with traditional risk factors, this marker may help to better direct preventive measures in this population

Trimethylamine-N-oxide (TMAO) predicts fatal outcomes in community-acquired pneumonia patients without evident coronary artery disease

The pro-atherosclerotic metabolite trimethylamine-N-oxide (TMAO) is a risk factor for incident cardiovascular events and a potentially modifiable mediator of chronic inflammation through broad-spectrum antibiotic treatment by changing the microbiome. Whether TMAO is associated with adverse clinical outcomes in acute inflammatory community-acquired pneumonia (CAP) patients is unknown.; A total of 317 CAP patients from a previous Swiss multicenter trial were prospectively followed for a median of 6.1years. TMAO plasma levels were measured by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We used Cox regression models to investigate associations between baseline TMAO levels and all-cause mortality.; Six-year mortality was 45.1%, and 18.9% of the patients had coronary artery disease (CAD). Median admission TMAO (μmolL(-1)) levels were significantly higher in non-survivors compared to survivors (4.1 [interquartile range (IQR), 2.2-7.2] vs. 2.5 [IQR, 1.5-4.1]; p>0.001). A strong association between TMAO and 6-year all-cause mortality was found for patients without CAD (adjusted hazard ratio (HR) 1.9 ([95% CI 1.2-3.1]; p>0.05). In patients with known CAD, no such association was found (adjusted HR 0.6 (0.2-1.6); p=0.309, interaction p=0.009). In patients without antibiotic pretreatment receiving antibiotic treatment, TMAO significantly decreased from admission to day seven (median, 3.9 [IQR, 2.1-7.5] vs. 3.1 [IQR, 1.4-6.6]; p>0.01).; TMAO is associated with long-term fatal outcomes in CAP patients without evident CAD and modifiable through antibiotic treatment. Whether chronic modulation of TMAO by targeting the microbiome reduces mortality risk needs to be evaluated in future interventional trials

Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study

AbstractBackground: As part of the immune defense during infection, an increase in enzyme activity of indoleamine 2,3-dioxygenase (IDO) leads to a breakdown of tryptophan to kynurenine. In previous animal studies, therapeutic antagonism of IDO resulted in reduced sepsis mortality. We investigated the prognostic ability of tryptophan, serotonin, kynurenine and IDO (represented by the ratio of kynurenine/tryptophan) to predict adverse clinical outcomes in patients with community-acquired pneumonia (CAP). Methods: We measured tryptophan, serotonin and kynurenine on admission plasma samples from CAP patients included in a previous multicenter trial by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We studied their association with inflammation (C-reactive protein), infection (procalcitonin) and clinical outcome. Results: Mortality in the 268 included patients was 45% within 6 years of follow-up. IDO and kynurenine showed a strong positive correlation with markers of infection (procalcitonin) and inflammation (C-reactive protein) as well as sepsis and CAP severity scores. Tryptophan showed similar, but negative correlations. In a multivariate regression analysis adjusted for age and comorbidities, higher IDO activity and lower tryptophan levels were strongly associated with short-term adverse outcome defined as death and/or ICU admission within 30 days with adjusted odds ratios of 9.1 [95% confidence interval (CI) 1.4-59.5, p=0.021] and 0.11 (95% CI 0.02-0.70, p=0.021). Multivariate analysis did not reveal significant associations for kynurenine and serotonin. Conclusions: In hospitalized CAP patients, higher IDO activity and lower tryptophan levels independently predicted disease severity and short-term adverse outcome. Whether therapeutic modulation of IDO has positive effects on outcome needs further investigation

Admission levels of asymmetric and symmetric dimethylarginine predict long-term outcome in patients with community-acquired pneumonia

During infection, there is an activation of the L-arginine-nitric-oxide pathway, with a shift from nitric oxide synthesis to a degradation of L-arginine to its metabolites, asymmetric and symmetric dimethylarginine (ADMA and SDMA). However, the prognostic implications for short-term or long-term survival remains unclear. We investigated the association of L-arginine, ADMA, and SDMA with adverse clinical outcomes in a well-defined cohort of patients with community-acquired pneumonia (CAP).; We measured L-arginine, ADMA, and SDMA in 268 CAP patients from a Swiss multicenter trial by mass spectrometry and used Cox regression models to investigate associations between blood marker levels and disease severity as well as mortality over a period of 6 years.; Six-year mortality was 44.8%. Admission levels of ADMA and SDMA (μmol/L) were correlated with CAP severity as assessed by the pneumonia severity index (r = 0.32, p &lt; 0.001 and r = 0.56, p &lt; 0.001 for ADMA and SDMA, respectively) and higher in 6-year non-survivors versus survivors (median 0.62 vs. 0.48; p &lt; 0.001 and 1.01 vs. 0.85; p &lt; 0.001 for ADMA and SDMA, respectively). Both ADMA and SDMA were significantly associated with long-term mortality (hazard ratios [HR] 4.44 [95% confidence intervals (CI) 1.84 to 10.74] and 2.81 [95% CI 1.45 to 5.48], respectively). The effects were no longer significant after multivariate adjustment for age and comorbidities. No association of L-arginine with severity and outcome was found.; Both ADMA and SDMA show a severity-dependent increase in patients with CAP and are strongly associated with mortality. This association is mainly explained by age and comorbidities.; ISRCTN95122877 . Registered 31 July 2006