Impact of general vs. neuraxial anesthesia on neonatal outcomes in non-elective cesarean sections

Background: Cesarean section is a common surgical procedure, usually performed under neuraxial anesthesia and, more rarely, under general anesthesia. The choice of anesthesia in cesarean sections can significantly influence neonatal outcomes, especially in urgent and emergency cases. Previous studies have shown mixed results, often confounded by the inclusion of both elective and emergency cesarean section cases, varying statistical methods, and a focus solely on resuscitation immediate-term neonatal outcomes. Objective: This study aims to use robust statistical methods to evaluate the impact of anesthesia type on immediate and longer-term neonatal outcomes in urgent and emergency cesarean section cases, where additional detrimental factors might influence this relationship. Methods: We analyzed 395 women who underwent non-elective cesarean sections between 2021 and 2023. Inverse probability of treatment weighting (IPTW) served to focus on the role of anesthesia type eliminating confounding variables effect, in simulated randomized controlled trial conditions. Results: General anesthesia increases odds of neonatal resuscitation (OR 6.1, p < 0.001), NICU admission (OR 1.8, p: 0.04), and a 15% lower Apgar score at 1 min (p: 0.02). General anesthesia also increased NICU admission rate for respiratory insufficiency (OR 7.6, p < 0.001), the need for oxygen (OR 4.8, p: 0.003) and CPAP (OR 3.6, p < 0.001) in NICU. Negative controls and consistent sensitivity analyses further validated the robustness of our findings. Conclusion: General anesthesia in non-elective cesarean sections is associated with worse neonatal outcomes, extending beyond the resuscitation phase to sustained NICU morbidity. Our study provides novel insights into the specific neonatal resuscitation maneuvers required when general anesthesia is used, enhancing clinicians preparedness for managing high-risk deliveries. These findings underscore the critical importance of anesthesia choice, advocate for the preference of neuraxial techniques, and highlight the need for further research into long-term neonatal outcomes

Attitudes, perceptions, and knowledge of the population on End-of-Life and Advance Treatment Declaration: an observational study in Southern Italy

In an advanced scientific and technological context, where it is now tangible the possibility of interfering indefinitely in the process of dying, it becomes necessary to disseminate knowledge about end of life that, for the great variety of areas that it invests, presents many controversial aspects. With the Law no. 219/2017, the right of self-determination and freedom of treatment of the patient is enshrined, aspects that to date still remain too little discussed. An online survey was conducted from December 2019 to February 2020, among the population residing in the provinces of Lecce and Brindisi, spread thanks to the collaboration of local authorities. A large part of the sample (82.4%, N=333) claims the right to self-determination, stating that therapeutic decisions are up to the patient who has signed his advance treatment dispositions, declared absolutely binding for 50% (N=205) of the sample. However, there is still a lack of information about how to draw up advance treatment agreements (AADs). 12.6% (N=51) of those interviewed stated that they knew nothing about it and only 32.9% (N=133) felt ready and adequately informed to make their own declarations. Another peculiar aspect is that topics such as euthanasia and assisted suicide seem to be considered at the margins of acceptability among End-of-Life instances. The results of the study show that knowledge on the subject has definitely improved over the years and that in most of the issues addressed, the population has an adequate degree of preparedness even though there is still some skepticism in dealing with issues such as assisted suicide and euthanasia. Future research could explore the possibility of identifying effective training tools and communication strategies that can be used by the widest possible segment of the population

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.publishedVersio

Global burden of cardiovascular diseases and risk factors, 1990-2019 : Update from the GBD 2019 Study

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases

Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Rigorous analysis of levels and trends in exposure to leading risk factors and quantification of their effect on human health are important to identify where public health is making progress and in which cases current efforts are inadequate. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a standardised and comprehensive assessment of the magnitude of risk factor exposure, relative risk, and attributable burden of disease. Methods: GBD 2019 estimated attributable mortality, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 87 risk factors and combinations of risk factors, at the global level, regionally, and for 204 countries and territories. GBD uses a hierarchical list of risk factors so that specific risk factors (eg, sodium intake), and related aggregates (eg, diet quality), are both evaluated. This method has six analytical steps. (1) We included 560 risk–outcome pairs that met criteria for convincing or probable evidence on the basis of research studies. 12 risk–outcome pairs included in GBD 2017 no longer met inclusion criteria and 47 risk–outcome pairs for risks already included in GBD 2017 were added based on new evidence. (2) Relative risks were estimated as a function of exposure based on published systematic reviews, 81 systematic reviews done for GBD 2019, and meta-regression. (3) Levels of exposure in each age-sex-location-year included in the study were estimated based on all available data sources using spatiotemporal Gaussian process regression, DisMod-MR 2.1, a Bayesian meta-regression method, or alternative methods. (4) We determined, from published trials or cohort studies, the level of exposure associated with minimum risk, called the theoretical minimum risk exposure level. (5) Attributable deaths, YLLs, YLDs, and DALYs were computed by multiplying population attributable fractions (PAFs) by the relevant outcome quantity for each age-sex-location-year. (6) PAFs and attributable burden for combinations of risk factors were estimated taking into account mediation of different risk factors through other risk factors. Across all six analytical steps, 30 652 distinct data sources were used in the analysis. Uncertainty in each step of the analysis was propagated into the final estimates of attributable burden. Exposure levels for dichotomous, polytomous, and continuous risk factors were summarised with use of the summary exposure value to facilitate comparisons over time, across location, and across risks. Because the entire time series from 1990 to 2019 has been re-estimated with use of consistent data and methods, these results supersede previously published GBD estimates of attributable burden. Findings: The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure. Global declines also occurred for tobacco smoking and lead exposure. The largest increases in risk exposure were for ambient particulate matter pollution, drug use, high fasting plasma glucose, and high body-mass index. In 2019, the leading Level 2 risk factor globally for attributable deaths was high systolic blood pressure, which accounted for 10·8 million (95% uncertainty interval [UI] 9·51–12·1) deaths (19·2% [16·9–21·3] of all deaths in 2019), followed by tobacco (smoked, second-hand, and chewing), which accounted for 8·71 million (8·12–9·31) deaths (15·4% [14·6–16·2] of all deaths in 2019). The leading Level 2 risk factor for attributable DALYs globally in 2019 was child and maternal malnutrition, which largely affects health in the youngest age groups and accounted for 295 million (253–350) DALYs (11·6% [10·3–13·1] of all global DALYs that year). The risk factor burden varied considerably in 2019 between age groups and locations. Among children aged 0–9 years, the three leading detailed risk factors for attributable DALYs were all related to malnutrition. Iron deficiency was the leading risk factor for those aged 10–24 years, alcohol use for those aged 25–49 years, and high systolic blood pressure for those aged 50–74 years and 75 years and older. Interpretation: Overall, the record for reducing exposure to harmful risks over the past three decades is poor. Success with reducing smoking and lead exposure through regulatory policy might point the way for a stronger role for public policy on other risks in addition to continued efforts to provide information on risk factor harm to the general public

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12.2 million (95% UI 11.0-13.6) incident cases of stroke, 101 million (93.2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6.55 million (6.00-7.02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11.6% 10.8-12.2] of total deaths) and the third-leading cause of death and disability combined (5.7% 5.1-6.2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70.0% (67.0-73.0), prevalent strokes increased by 85.0% (83.0-88.0), deaths from stroke increased by 43.0% (31.0-55.0), and DALYs due to stroke increased by 32.0% (22.0-42.0). During the same period, age-standardised rates of stroke incidence decreased by 17.0% (15.0-18.0), mortality decreased by 36.0% (31.0-42.0), prevalence decreased by 6.0% (5.0-7.0), and DALYs decreased by 36.0% (31.0-42.0). However, among people younger than 70 years, prevalence rates increased by 22.0% (21.0-24.0) and incidence rates increased by 15.0% (12.0-18.0). In 2019, the age-standardised stroke-related mortality rate was 3.6 (3.5-3.8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3.7 (3.5-3.9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62.4% of all incident strokes in 2019 (7.63 million 6.57-8.96]), while intracerebral haemorrhage constituted 27.9% (3.41 million 2.97-3.91]) and subarachnoid haemorrhage constituted 9.7% (1.18 million 1.01-1.39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79.6 million 67.7-90.8] DALYs or 55.5% 48.2-62.0] of total stroke DALYs), high body-mass index (34.9 million 22.3-48.6] DALYs or 24.3% 15.7-33.2]), high fasting plasma glucose (28.9 million 19.8-41.5] DALYs or 20.2% 13.8-29.1]), ambient particulate matter pollution (28.7 million 23.4-33.4] DALYs or 20.1% 16.6-23.0]), and smoking (25.3 million 22.6-28.2] DALYs or 17.6% 16.4-19.0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries

Pulmonary and Extrapulmonary Manifestations in Hospitalized Children with Mycoplasma Pneumoniae Infection

Mycoplasma pneumoniae (MP) is one of the main causes of both upper and lower respiratory infections in school-aged children, accounting for up to 40% of community-acquired pneumonia. Younger children are also affected, and extrapulmonary manifestations have been recently reported in the pediatric population. We carried out a retrospective analysis of MP-positive patients admitted to the Pediatric Emergency Unit of S. Orsola Malpighi University Hospital in Bologna, the largest tertiary pediatric referral center in the Emilia–Romagna region, Northern Italy, between 2012 and 2020. We identified 145 patients with MP infection (82 males and 63 females), 27% of which were younger than 2 years; the median age was 5 years (interquartile range 1–9). The clinical presentation partially differed between age groups. School-aged children were more likely to have a chest X-ray-confirmed pneumonia (p = 0.013), while younger children required oxygen therapy more often (p = 0.048). Seventy-four children (51%) showed extrapulmonary manifestations, mainly gastrointestinal (30%) and dermatological (14%). Neurological symptoms were more frequent in children older than 6 years (p = 0.006). The rate of other extrapulmonary manifestations did not differ significantly between age groups. This study shows that MP infection is a frequent cause of pediatric hospitalization, including of children younger than 2 years. Clinicians should be aware of the variable clinical expressions of MP, including extrapulmonary manifestations, to achieve a correct diagnosis and determine appropriate treatment