Colorectal cancer (CRC) incidence in Finland has risen steadily. Given development in cancer treatments in recent decades, disease-specific data on the long-term prognosis of patients may be obsolete. Thus, this study aimed to report 5-year disease-specific survival (DSS) and relative survival based on tumour spread and site among CRC patients diagnosed between 1991 and 2015 in Finland.We conducted a population-based registry study among 59 465 CRC patients identified from the Finnish Cancer Registry.The 5-year DSS for all CRC patients was 56.7% [95% confidence interval (CI) 56.3–57.1%] for 1991 through 2015. Tumour site-specific survival has improved for the period 2006–2015 versus 1991–2005 for right-sided colon cancer from 54.8% (95% CI 53.8–55.8%) to 59.9% (95% CI 58.7–61.1%), for left-sided colon cancer from 54.1% (95% CI 52.9–55.3%) to 61.0% (95% CI 59.8–62.2%) and for rectal cancer from 53.6% (95% CI 52.2–55.0%) to 62.3% (95% CI 61.3–63.3%). The 5-year relative survival for the period 2006 through 2015 was 93.6% for localised disease (stage I); 84.2% for locally advanced tumour invading adjacent structures (stage II); 68.2% for regional disease with regional lymph node metastases (stage III); and 14.0% for metastatic disease (stage IV).This study confirms that survival for CRC has improved in recent decades in Finland, mirroring observations from other Western countries. However, the classification of tumour spread within the Finnish Cancer Registry differs slightly from the TNM classification, thereby limiting the generalisability of these results.The online version contains supplementary material available at 10.1186/s12885-022-09460-0. After prostate and breast cancers, colorectal cancer (CRC) is the third most common cancer in Finland with more than 3500 new cases occurring in 2018 [FCR is a population-based registry cataloguing data for each cancer case in Finland since 1952. The completeness of the data for CRC is 97.4%, exceeding 99% for all solid tumours , 4. The Previous studies on stage-specific survival for CRC in Finland either relied on small and local study populations or are dated. In a large cohort study in southwest Finland from 1971 to 1990 with a population of 433 000, an increasing age-adjusted incidence for colon cancer reaching 13.5/100 000 for men and 13.1/100 000 for women by 1990 was noted, compared to 11.1/100 000 for men and 7.1/100 000 for women for rectal cancer . No remaIn this nationwide registry study, we aimed to report 5-year disease-specific survival (DSS) and relative survival according to tumour spread and tumour site among CRC patients diagnosed between 1991 and 2015.Our study comprises all patients diagnosed with CRC in Finland from 1991 through 2015. We requested and received information about patients (gender and age at diagnosis), tumour-specific data  and time and cause of death data from FCR. Causes of death were coded using the International Classification of Diseases, tenth edition (ICD-10), and considered disease-specific when recorded as C18–C20 . We divided data into two main periods according to the time of diagnosis – the former, 1991 through 2005 and the latter, 2006 through 2015 – as well as into five smaller time periods: 1991–1995, 1996–2000, 2001–2005, 2006–2010 and 2011–2015.n = 1180) and patients with missing information on the diagnosis (n = 30). One patient was excluded because of a missing date of death.Out of 59 896 cancer cases in total, we identified 59 465 individual patients .Tumour location was analysed separately for the right colon, left colon and rectum. The right colon constitutes the caecum to the transverse colon and the left colon starts at the splenic flexure of the colon . The recFCR obtains information on the cause of death from Statistics Finland, which in turn obtains the information from the deceased’s death certificate, which is filed by the treating physician. In addition, a specialist in forensic medicine approves all death certificates before they are ultimately registered.p value. We reported 95% confidence intervals (CIs) for 5-year survival and compared the CIs between groups. DSS was calculated as the time of diagnosis until death from CRC  or until the end of the follow-up period on 31 December 2016. Deaths unrelated to CRC  were censored. Subgroup analyses were performed based on the tumour site and time periods. The relative survival analyses were performed using the relative survival estimation proposed by Ederer and Heise [p < 0.05 as statistically significant. All statistical analyses were performed using SPSS Statistics version 25 .We analysed the median age at diagnosis using the interquartile range (IQR), gender distribution, tumour FCR classification and tumour location. Disease-specific survival (DSS) was calculated according to the Kaplan–Meier method using the log-rank analysis to determine the nd Heise . We compnd Heise . We consThe study protocol was approved by the National Institute of Health and Welfare (THL/722/5.05.00/2018).This study included a total of 58 254 CRC patients  for the period 1991 through 2015. The number of patients in each FCR class varied depending on how the categories were registered during different time periods. Since the early 1990s, both FCR classes 5  and 6  have continued increasing, whereas FCR class 1  has continued declining , 5-year DSS was 80.5% (95% CI 80.1–81.7%) for the period 1991 through 2005 and 89.9%  through to the last time period (2011–2015) for localised colon cancer, increasing from 79.2% to 91.4%, and for localised rectal cancer, increasing from 69.4% to 90.5% (FCR 1). This trend also emerged for patients with local lymph node metastasis (FCR 2) colon cancer, increasing from 49.1% to 62.0%, and rectal cancer, increasing from 44.0% to 68.9% Tables  and 4. FComparing the earlier time period with the later (1991–2005 vs. 2006–2015), 5-year DSS for right-sided colon cancer was 54.8% (95% CI 53.8–55.8%) versus 59.9% (95% CI 58.7–61.1%), 54.1% (95% CI 52.9–55.3%) versus 61.0% (95% CI 59.8–62.2%) for left-sided colon cancer and 53.6% (95% CI 52.2–55.0%) versus 62.3% (95% CI 61.3–63.3%) for rectal cancer.In the period 2006 through 2015, 5-year DSS among patients diagnosed with localised disease (FCR 1) remained rather similar for those with right-sided colon cancer, left-sided colon cancer and rectal cancer  and relative survival among 58 254 patients with CRC in Finland. We found that, over time, when comparing patients diagnosed between 1991 and 2005 with those diagnosed between 2006 and 2015, both DSS and relative survival improved. Cancer-specific data on staging received from FCR relies on FCR’s own classification for tumour spread . It is, Our results for 5-year relative survival among patients diagnosed in the period 2006 through 2015 with local, regional and metastatic CRC  agree with population-based studies from the US, the Netherlands and Australia –16. The For patients with locally advanced disease with the tumour invading adjacent tissues (FCR 5), both 5-year DSS and relative survival were seemingly better in the earlier time period. However, this may be explained by the low volume of patients in the earlier time periods Tables A–B. BecaFCR classes 3  and 4  represent problematic groups, roughly corresponding to TNM stages II through IV and III through IV, respectively, as shown in Table For patients with localised disease (FCR 1), survival seems similar when comparing right-sided colon, left-sided colon and rectal cancers. For lymph node-positive (FCR 2) and metastatic cancer (FCR 6) patients, we found that 5-year DSS was worse among those with right-sided colon cancer compared with patients with left-sided colon or rectal cancer. Similar findings were noted in a systematic review  and in aIn general, improved survival may result from stage migration when patients over time are staged more accurately and, hence, survival across all of the staging classes impacted improves. The reliable staging of CRC requires at least 12 regional lymph nodes for pathological examination. Pathological reporting based on less than 12 regional lymph nodes results in low-quality staging and represents a poor prognostic marker itself –23. ModeOne strength of our study lies in the large cohort of data from FCR, which records information on every cancer case in Finland and features an excellent coverage. However, we must regard the FCR classification of tumour spread as a limitation, given that it is difficult to compare these data precisely with data relying on the UICC TNM staging. Despite this limitation, the use of this kind of classification also allows for the inclusion of cases with incomplete information. Recently, one study showed that the FCR classification agrees fairly well with the TNM staging classification .In conclusion, this population-based study in Finland investigated current survival among CRC patients according to tumour spread, comparable to the TNM staging classification. We found that survival has improved in nearly all subgroups in recent decades, mirroring findings from other Western countries. We confirmed that survival among colon cancer patients with right-sided disease is generally worse when compared with left-sided disease. In future, these results may be used as a reference when evaluating local treatment outcomes. However, caution must be taken when comparing the FCR classification with the TNM staging. Recording stage-specific information for patients’ cancers remains of utmost importance. Doing so aids both clinical and international comparisons, particularly if data from FCR can be retrieved according to the UICC TNM staging classification.Additional file 1.Additional file 2.Additional file 3.Additional file 4.Additional file 5.


The associations of maternal cigarette smoking with congenital anomalies in offspring have been inconsistent. This study aimed to clarify the associations of the timing and intensity of maternal cigarette smoking with 12 subtypes of birth congenital anomalies based on a nationwide large birth cohort in the USA.We used nationwide birth certificate data from the US National Vital Statistics System during 2016–2019. Women reported the average daily number of cigarettes they consumed 3 months before pregnancy and in each subsequent trimester during pregnancy. Twelve subtypes of congenital anomalies were identified in medical records. Poisson regression analysis was used to estimate the risk ratios (RRs) with 95% confidence intervals (CIs) for 12 subtypes of congenital anomalies associated with the timing  and intensity  of maternal cigarette smoking.P > 0.05).Among the 12,144,972 women included, 9.3% smoked before pregnancy and 7.0%, 6.0%, and 5.7% in the first, second, and third trimester, respectively. Maternal smoking before or during pregnancy significantly increased the risk of six subtypes of birth congenital anomalies , even as low as 1–5 cigarettes per day. The adjusted RRs (95% CIs) for overall birth congenital anomalies  among women who smoked 1–5, 6–10, and ≥ 11 cigarettes per day before pregnancy were 1.31 (1.22–1.41), 1.25 (1.17–1.33), and 1.35 (1.28–1.43), respectively. Corresponding values were 1.23 (1.14–1.33), 1.33 (1.24–1.42), 1.33 (1.23–1.43), respectively, for women who smoked cigarettes in the first trimester; 1.32 (1.21–1.44), 1.36 (1.26–1.47), and 1.38 (1.23–1.54), respectively, for women who smoked cigarettes in the second trimester; and 1.33 (1.22–1.44), 1.35 (1.24–1.47), and 1.35 (1.19–1.52), respectively, for women who smoked cigarettes in the third trimester. Compared with women who kept smoking before and throughout pregnancy, women who never smoked had significantly lower risk of congenital anomalies , but women who smoked before pregnancy and quitted during each trimester of pregnancy had no reduced risk (all Maternal smoking before or during pregnancy increased the risk of several birth congenital anomalies, even as low as 1–5 cigarettes per day. Maternal smokers who stopped smoking in the subsequent trimesters of pregnancy were still at an increased risk of birth congenital anomalies. Our findings highlighted that smoking cessation interventions should be implemented before pregnancy.The online version contains supplementary material available at 10.1186/s12916-021-02196-x. Congenital anomalies, also known as congenital malformations or birth defects, can be defined as structural or functional anomalies that are diagnosed prenatally or after delivery . GloballIn the USA, nearly 16.0% of women aged 25–44 years were current cigarette smokers in 2015 . It meanN = 12,144,972), this study was aimed to examine the associations of the timing  and intensity (number of cigarettes consumed per day) of maternal cigarette smoking with 12 subtypes of birth congenital anomalies.Based on a nationwide large birth cohort data in the USA (www.cdc.gov/nchs/nvss/births.htm). The birth certificate data from the NVSS are de-identified and do not include any protected health information. The data are publically available [This study used nationwide birth certificate data from the National Vital Statistics System (NVSS) in the USA 2016-2019). The NVSS is a joint program led by the US Centers for Disease Control and Prevention and all US states. It collected data on a wide range of maternal and infant demographic and health information. Standardized questionnaires and registration procedures have been developed and recommended for all states and the District of Columbia in the USA. Two worksheets have been developed since 2003, including the mother’s worksheet and the facility worksheet. The mother`s worksheet compiles mother data around the time of delivery . The facility worksheet compiles other data appearing in medical records . More details about NVSS data collection can be found at the official website  in order to only include adult women of reproductive age, women with twin or multiple births  because they differed from the singletons with congenital anomalies [n = 396,324) because these chronic conditions were strong risk factors for birth congenital anomalies [n = 67,209), birth congenital anomalies , or on covariates . This left a total of 12,144,972 live singleton births included for the final data analysis. Figure In this study, we used NVSS data from 2016 to 2019 because all US states and the District of Columbia had completely implemented the 2003 version of Standard Certificate of Live Birth to collect birth information since 2016. A total of 15,379,982 live births registered in the NVSS from 2016 to 2019 were preliminarily included in the study. We then excluded women aged < 18 or ≥ 50 years , parity, infant sex, gestational age at delivery, and prenatal care visits were obtained from the facility worksheet.2 based on the World Health Organization guidelines [We categorized covariates as follows: maternal age at delivery , race/ethnicity , educational level , marital status (married or unmarried), maternal pre-pregnancy body mass index (BMI) , eclampχ2 test for categorical variables and Wilcoxon test for continuous variables. We first used Poisson regression analysis to estimate the associations of maternal cigarette smoking status (yes versus no) before or during pregnancy with each of 12 subtypes of congenital anomalies using women who did not smoke cigarettes in the corresponding period as the reference. We adjusted for several covariates, including maternal age at delivery, race/ethnicity, educational level, marital status, maternal pre-pregnancy BMI, eclampsia, gestational hypertension, gestational diabetes, parity, infant sex, gestational age at delivery, and total number of prenatal care visits. These potential confounders were selected based on the literature  as well as the information that was available on the birth certificate. We then estimated the risk ratios (RRs) and 95% confidence intervals (CIs) of birth congenital anomalies  according to smoking intensity before and during each trimester of pregnancy. We also examined the association of smoking cessation in different trimesters of pregnancy with overall birth congenital anomalies using women who kept smoking before and throughout pregnancy as the reference. We performed four sensitivity analyses to test the stability of our main findings , including the exclusion of women with cesarean section, the exclusion of those with eclampsia, gestational hypertension or gestational diabetes, the exclusion of those with preterm delivery, and the use of imputation analyses  to dealp < 0.0001). Detailed characteristics of the study population are shown in Table A total of 12,144,972 women with live singleton births were included, with a mean age at delivery of 29 years (interquartile range 25–33 years). 9.3% of the women smoked cigarettes before pregnancy, respectively 7.0%, 6.0%, and 5.7% in the first, second, and third trimesters. In general, women who smoked cigarettes before or during pregnancy tended to be younger and non-Hispanic white, to have a low educational level, to be unmarried, obese, and multiparous   of cleft lip with or without cleft palate of infants born to women who smoked cigarettes before pregnancy, and in the first, second, and third trimesters were 1.28 (1.18–1.38), 1.26 (1.16–1.37), 1.26 (1.15–1.38), and 1.24 (1.13–1.36), respectively .Regarding overall congenital anomalies , the adjusted RRs (95% CIs) were 1.30 (1.25–1.36) for women who smoked before pregnancy and 1.30 (1.24–1.36), 1.35 (1.27–1.43), and 1.34 (1.26–1.42) for women who smoked in the first, second, and third trimesters, respectively  of 0.990.91–1.08), 1.06(0.95–1.19), and 0.93 (0.78–1.10), respectively ) to 0.0028 (0.05/(3*6)) when subgroups ranged from 21  of cleft lip with or without cleft palate of infants born to women who smoked 1–5, 6–10, and ≥ 11 cigarettes per day before pregnancy were 1.33 (1.16–1.52), 1.19 (1.05–1.35), and 1.32 1.18–1.47), respectively. The corresponding values were 1.26 (1.10–1.45), 1.21 (1.07–1.38), and 1.33 (1.15–1.53) for women who smoked in the first trimester; 1.22 (1.06–1.41), 1.26 (1.10–1.43), and 1.33 (1.11–1.59) for women who smoked in the second trimester; and 1.20 (1.05–1.38), 1.23 (1.07–1.41), and 1.33 (1.10–1.63) for women who smoked in the third trimester. For congenital diaphragmatic hernia and hypospadias, the significant association was observed for the specific intensity of maternal cigarette smoking in specific trimester   for women who smoked 1–5, 6–10, and ≥ 11 cigarettes per day before pregnancy were 1.31 1.22–1.41), 1.25 (1.17–1.33), and 1.35 (1.28–1.43), respectively. The corresponding values were 1.23 (1.14–1.33), 1.33 (1.24–1.42), and 1.33 (1.23–1.43) for women who smoked cigarettes in the first trimester; 1.32 (1.21–1.44), 1.36 (1.26–1.47), and 1.38 (1.23–1.54) for women who smoked in the second trimester; and 1.33 (1.22–1.44), 1.35 (1.24–1.47), and 1.35 (1.19–1.52) for women who smoked in the third trimester , before pregnancy or during each trimester of pregnancy significantly increased the risk of six specific subtypes of congenital anomalies . Compared with persistent smokers before and throughout pregnancy, a significantly lower risk of congenital anomalies was observed for never smokers, but no reduced risk was observed for women who smoked before pregnancy and quitted during each trimester of pregnancy.n = 838,265) than ours . The Danish study also did not adjust for potentially important covariates which we have adjusted for in our analysis . In addition, disparities in definitions of “overall congenital anomalies” may also contribute to the inconsistent results. However, when we used having any of the 12 congenital anomalies to define “overall congenital anomalies,” we still found an increased risk of overall congenital anomalies for maternal smoking (data not shown).In the present study, we found an increased risk of overall congenital anomalies in offspring born to mothers who smoked cigarettes during pregnancy, which contrasts with a previous large population-based cohort study using data from the Danish Medical Birth Register, which did not find an overall increased risk of congenital anomalies  . It shouSince different anomalies can have different etiologies, defect-specific analyses may better reflect the association between maternal cigarette smoking and congenital anomalies. A meta-analysis of 6 case-control studies  published between 2000 and 2010 revealed that maternal smoking during pregnancy significantly increased the risk of cleft lip with or without cleft palate  . The DanIn addition to clarifying the associations of maternal cigarette smoking with birth congenital anomalies, a novel finding of this study was that maternal cigarette smoking either before pregnancy or during each trimester of pregnancy significantly increased the risk of birth congenital anomalies, suggesting that there is no safe period of maternal smoking, which has been seldom reported in the previous studies mentioned above. It is interesting that the associations of smoking with congenital anomalies did not change significantly according to different trimesters. One speculative, possible explanation would be that the detrimental effects of maternal smoking on congenital anomalies mainly originate from an earlier period in pregnancy: morphogenesis is influenced mainly during the first days of embryogenesis, whereas later days of pregnancy involve mostly about growth of the embryo. The observed similar association between maternal smoking in the second and third trimesters of pregnancy and congenital anomalies might be due to the fact that the majority of women who smoked in early pregnancy continued to smoke cigarettes throughout pregnancy.Another important finding of this study was that smoking exposure within three months before pregnancy, but with cessation during the pregnancy, had the similar risk of birth congenital anomalies compared with persistent smokers before and during pregnancy. One possible explanation was the detrimental action of maternal smoking on some genes—genetic or epigenetic—of the ovules  . Anothern = 1,413,811; 1983–1996) showed a marginally positive association between light smokers (< 10 cigarettes per day) and any malformation  [The third important finding of our study was that mothers who smoked only few cigarettes (1–5 cigarettes per day) had an increased risk of congenital anomalies compared with non-smokers, suggesting there is no safe level of cigarette smoking for pregnant women. Similarly, Chung, et al.  used the98–1.05) . However98–1.05) . Another98–1.05) . The pos98–1.05) , which mFinally, it should be mentioned that magnitudes of the positive association between maternal smoking and congenital anomalies in our study were somewhat higher than those in previous studies mentioned above. We speculate that this may be due to variability in exposure assessment  and case ascertainment . In addition, many previous studies were based on relatively small number of cases on congenital anomalies and with adjustment for a limited number of potential confounders. Further large well-designed prospective cohort studies are needed to warrant the observed association and to examine the possible explanations.The main strengths of this study include the population-based cohort design, the large sample size of over 12 million live births, the detailed examination of the associations between the timing and intensity of maternal cigarette smoking and many congenital anomalies subtypes considered (including rare subtypes), the adjustment for several  covariates, and the sensitivity analyses used to confirm our findings. However, this study also has several limitations. First, there were limitations to use birth certificate data for assessing the association with birth defects. Data on pregnancy complications, and comorbid conditions tended to be underreported on the birth certificates . HoweverIn conclusion, our findings showed that maternal cigarette smoking, even at a low intensity (1–5 cigarettes per day), before pregnancy or during either trimester of pregnancy significantly increased the risk of birth congenital anomalies. Women who smoked before pregnancy and quitted during each trimester of pregnancy still had an increased risk of congenital anomalies in offspring than women who did not smoke before and throughout pregnancy. Therefore, smoking cessation interventions should be implemented before pregnancy. Early initiation of pre-pregnancy counseling is of paramount importance which should include an explanation of the adverse effects of cigarette smoking on both mothers and their children including congenital anomalies and suggest on not to start smoking (for never smokers) or to stop smoking completely (for current smokers) both before and during pregnancy. The current study also provided strong evidence to strengthen the recommendation proposed by the US public health service  for health care providers to help maternal smokers to quit smoking . InterveAdditional file 1. Supplementary results. Table S1. Associations of maternal smoking cessation during pregnancy with overall birth congenital anomalies. Table S2. Sensitivity analyses of associations between the timing of maternal cigarette smoking and birth congenital anomalies.


Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia.P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7.Individual patient data from eligible antimalarial efficacy studies of uncomplicated p < 0.001).A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0–19.7 g/dL) in Africa, 11.6 g/dL (range 5.0–20.0 g/dL) in Asia and 12.3 g/dL (range 6.9–17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4%  of patients from Africa, 3.3%  from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age , high parasitaemia  and delayed parasite clearance . In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39–3.05], P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery.In patients with uncomplicated The online version contains supplementary material available at 10.1186/s12916-022-02265-9. Malaria remains a major cause of anaemia in malaria endemic countries, with a complex pathogenesis attributable to red cell destruction and haematopoietic suppression  that canP. falciparum infection and the clinical and demographic factors that underlie this. The aim of this study was to determine the pattern of haematological recovery following uncomplicated falciparum malaria and define the risk factors for moderately severe haematological outcomes at baseline and during early follow-up.To assess the comparative benefits of different antimalarial treatment regimens, it is critical to quantify the haematological impact attributable to P. falciparum transmission intensities. Data in the repository have been standardised and collated using methodology described previously in the WWARN Clinical Module Data Management and Statistical Analysis Plan [Haemoglobin concentrations are often not reported in antimalarial trial publications, even if these data are collected. Since a review of published literature would not provide sufficiently comprehensive information, the focus of this individual patient data meta-analysis was on studies identified in the WWARN repository. The WWARN repository contains data from 451 antimalarial efficacy studies in which patients were enrolled from locations in 69 countries, with a diverse range of P. falciparum malaria in non-pregnant patients that followed subjects prospectively for a minimum of 28 days and reported haemoglobin concentration (or haematocrit) at least at baseline (day 0). Investigators of the identified studies were invited to participate in this study group and information was made available on the WWARN website [P. falciparum malaria was defined as microscopy-proven falciparum malaria without features of severe malaria [The WWARN repository was searched in August 2015 for all antimalarial efficacy studies of uncomplicated  website . Uncompl malaria . PatientThe primary outcome of the analysis was the risk of moderately severe anaemia (Hb < 7 g/dL) on day 7 after initiation of treatment. Secondary outcomes included the mean fall in haemoglobin at day of nadir and day 7, the timing of nadir haemoglobin, risk of moderately severe anaemia at days 0 and 3, and the risk of a large reduction in haemoglobin from baseline, defined as a fractional fall in Hb of ≥ 25% on day 3 or 7.All statistical analyses were done using R  or Stata MP 15, based on an a priori statistical plan shared with data contributors .Haematocrit measurements were converted to haemoglobin concentrations using the following formula: Haemoglobin = (Haematocrit − 5.62)/2.60 . The timChanges in mean haemoglobin over time were examined, after stratifying by region, using linear mixed effects models. Fractional polynomial terms for time were fitted as random effects for patients to capture the nonlinear associations and random intercepts for patients and study site. All available haemoglobin measurements were included in these analyses. Additional analyses of mean haemoglobin over time within each region were undertaken, stratified by age group (< 5 years and ≥ 5 years).Plasmodium species infection, underweight (defined as weight-for-age Z-score <−2 for children younger than 5 years) [P. falciparum prevalence rate (PfPR) according to enrolment year and location [For all regression models, independent risk factors were identified following the strategy recommended by Collet . Covaria5 years) , high pa5 years) ), presenlocation , assuminAll data included in this analysis were obtained in accordance with ethical approvals from the countries of origin. The data are fully anonymised and cannot be traced back to individuals. This analysis did not require separate ethical approval according to the guidelines of the Oxford Central University Research Ethics Committee.P. falciparum clinical trials undertaken between 1991 and 2013 met the inclusion criteria and were available for analysis , with 2 studies (483 patients) excluding patients with a haemoglobin < 6 g/dL, 9 studies (5964 patients) excluding patients with a haemoglobin < 7 g/dL and 3 studies (566 patients) excluding patients with a haemoglobin < 8 g/dL. In 60 studies, haematological exclusion criteria were not stated; Additional file The median haemoglobin at enrolment was 9.9 g/dL (range 5.0–19.7 g/dL) in Africa, 11.6 g/dL (range 5.0–20.0 g/dL) in Asia and 12.3 g/dL (range 6.9–17.9 g/dL) in South America  and day 7  versus 2.3%  respectively; p < 0.001).Overall, 9.1%  of patients had moderately severe anaemia (Hb < 7 g/dl) on day 3 and 4.4%  on day 7. The risk of falling below 7 g/dL in people who did not have moderately severe anaemia at baseline was greater in Africa than in Asia on both day 3  versus 6.5% ; p < 0.001 for Africa and 23.00 (14.27–37.06), p < 0.001 for Asia), younger age (for age < 1 year compared to patients ≥ 12 years AOR = 12.81 (95%CI 6.79–24.17), p < 0.001 and AOR = 6.79 (95%CI 2.36–19.58), p < 0.001 and for age 1 to 4 years compared to patients ≥ 12 years AOR = 6.09 (95%CI 3.33–11.13), p < 0.001 and AOR = 2.87 (95%CI 1.84–4.47), p < 0.001) and parasitaemia > 100,000/μL (AOR = 1.78 (95%CI 1.42–2.24), p < 0.001 and 1.58 (1.10–2.27), p = 0.013) (Table p < 0.001) was an independent predictor of moderately severe anaemia whilst female sex (AOR = 0.80 (95%CI 0.69–0.93); p = 0.004) was protective. In Asia, female sex was an independent predictor (AOR = 1.51 (95%CI 1.15–1.99), p = 0.003) and mixed infection was protective (AOR = 0.44 (95%CI 0.24–0.80), p = 0.007). The effect of sex was explored by evaluating the models separately in children compared with adolescents and adults. In adolescents and adults (age ≥ 12 years), female sex was associated with moderately severe anaemia, and this reached statistical significance in Asia (AOR = 2.55 (95%CI 1.65–3.94), p < 0.001), but not Africa (AOR = 1.98 (95%CI 0.71–5.49), p = 0.191). In contrast, in children (age < 12 years) female sex was associated with a lower risk of moderately severe anaemia, reaching statistical significance in Africa (AOR = 0.78 (95%CI 0.67–0.91), p = 0.001), but not Asia (AOR = 0.98 (95%CI 0.73–1.32), p = 0.903).The following independent predictors of moderately severe anaemia at day 7 in both Africa and Asia were identified: moderately severe anaemia at baseline (AOR = 16.10 95%CI 12.59–20.60), .59–20.60d 23.00 1.27–37.06p < 0.001), but this was not the case in African patients (AOR = 1.01 (95%CI 0.56–1.82); p = 0.987). In Asia, the difference in risk between artemisinin- and non-artemisinin-based treatments remained when only the 8570 patients enrolled before 2007 (when artemisinin resistance was first described in the Greater Mekong Subregion) were included in the model (AOR = 1.98 (95%CI 1.39–2.82); p < 0.001). Overall, the risk factors for moderately severe anaemia on day 3 were similar to those at day 7, with patients treated with artemisinin-based therapy at significantly greater risk of moderately severe anaemia on day 3 in Asia (AOR = 3.27 (95%CI 2.42–4.42); p < 0.001), but not in Africa (AOR = 0.69 (95%CI 0.32–1.49); p = 0.343) ; 9–3.05; pr = 0.47; p < 0.001 adjusted for clustering of study site). A high baseline haemoglobin was associated with a greater risk of a large fractional fall (≥ 25%) on day 7 in Africa (AOR for every 1 g/dL increase in baseline haemoglobin = 1.52 (95%CI 1.40–1.65); p < 0.001) and in Asia (AOR for every 1 g/dL increase in baseline haemoglobin = 1.43 (95%CI 1.35–1.52); p < 0.001)  and Asia (AOR = 2.59 (95%CI 1.20–5.58); p = 0.015)  were parasitaemic on day 2 and 2.6% (358) were parasitaemic on day 3. The corresponding proportions in Asia were 14.9% (1339/8960) and 4.2% (375/8960). After controlling for confounding factors, the risk of moderately severe anaemia at day 7 was greater in patients with delayed parasite clearance in both Africa (AOR = 2.44 (95%CI 1.59–3.75); Methodological factors potentially contributing to bias are presented in Additional file Our study provides a detailed analysis of haemoglobin concentration kinetics in patients with falciparum malaria, enrolled across geographically diverse regions. The available data, exceeding > 70,000 individual data from patients of all ages, provides unprecedented power to define the factors associated with the acute fall in haemoglobin before and after treatment. Malaria is due to an intraerythrocytic infection which results in a reduction of red blood cells, intra- and extravascular haemolysis, bone marrow suppression and sequestration . The admAlthough the greatest fall in haemoglobin occurred before treatment in Africa, our analysis focused primarily on factors associated with the subsequent fall and recovery which may be more amenable to clinical intervention. Consistent with a recent pooled analysis from Africa , our stuThe baseline haemoglobin in patients with falciparum malaria varied substantially with age and parasite density at presentation. After controlling for confounding factors, significant site to site variation remained, likely reflecting variations in transmission intensity, host immunity and factors unrelated to malaria. Patients from Asia tended to be older than those enrolled in Africa, but after controlling for age there were minimal differences in haemoglobin between regions, either at baseline or during follow-up. Following treatment, the absolute and proportional reductions in haemoglobin were greater in patients from Asia compared to Africa and were correlated with the higher baseline haemoglobin in Asian patients. Hence, patients presenting with a low haemoglobin concentration were less likely to experience a further fall in their haemoglobin.Plasmodium parasitaemia in these regions will have an alternative diagnosis, such as bacterial sepsis, which is also associated with anaemia [The relationship between level of parasitaemia and degree of anaemia is complex , 179. In anaemia . Second, anaemia , 181.In Asia, the risk of anaemia at presentation increased with rising parasitaemia, peaking at 10,000 parasites/μL before decreasing thereafter. As transmission intensity in endemic parts of Asia is generally significantly lower than in Africa, immunity is less robust and a much greater proportion of infections will be symptomatic and of short duration. In this setting, anaemia will be related primarily to acute destruction of both parasitised and unparasitised red cells, the severity of which is correlated with the level of parasitaemia.Treatment with artemisinin-based therapy in Asia was associated with a twofold higher risk of moderately severe anaemia  within 7 days compared with non-artemisinin-based therapy, whereas in Africa, artemisinin-based treatment was not associated with an excess risk of early anaemia. This relationship was not attributable to the presence of artemisinin resistance. We hypothesise that rapid killing of intraerythrocytic parasites by artemisinins in non-immune Asian adults likely leads to more rapid clearance of whole red blood cells from the circulation than that occurring after slower acting drug treatments. In immune African patients, a greater proportion of infected red cells undergo targeted intraerythrocytic parasite removal (pitting) followed by a return to circulation, thus ameliorating the early development of anaemia . ReticulOur study has a number of limitations. The analysis focused on the acute haematological impact of malaria and the early recovery phase and did not address the influence of late treatment failure on subsequent recovery to baseline haemoglobin concentrations. This will be addressed in a subsequent analysis. Our estimates of the pattern of haemoglobin changes during the first few days after diagnosis may have been influenced by selection bias, as only a small subset of patients had multiple haemoglobin measurements during the first 7 days of follow-up. Although we did not employ a traditional systematic review to identify eligible studies, our analysis is the largest meta-analysis to date of patients treated for malaria in both Africa and Asia. This unprecedented data collection ensures robust parameter estimates and minimises the risk of inclusion bias. Furthermore, a systematic review would not preclude bias, since some studies recorded haemoglobin/haematocrit measurements but did not present these data in published manuscripts. Whilst the results of the current study are likely to be generalisable to Africa and Asia, the small number of patients from the Americas prevents the generalisability of our findings to this region. An additional potential cause of bias is the exclusion of patients from the original studies, prior to pooling, according to variable definitions of severe anaemia. Almost two-thirds of studies excluded patients with a haemoglobin < 5 g/dL, with a few studies excluding patients based on higher cut-offs and the remaining 30% having an unknown cut-off. Additional limitations of our study include the use of various methodologies to measure haematocrit or haemoglobin, a lack of a robust conversion factor to adjust haematocrit to haemoglobin in different studies’ populations and no reliable data on the following confounding factors that can influence haemoglobin and its recovery: the duration of prior parasitaemia (which has been shown to correlate with anaemia at presentation ), host gP. falciparum infection.In conclusion, the majority of patients with uncomplicated falciparum malaria had a modest fall in haemoglobin following treatment, before subsequent improvement in haemoglobin during recovery. Despite highly effective treatment, some patients remained at significant risk of moderately severe anaemia. Young children had a particularly high risk, likely related to lower immunity and high initial peripheral parasitaemia. The risk of anaemia is exacerbated by prolonged parasitaemia prior to presentation  or delayAdditional file 1: Table S1. Describes studies included in the analysis. Table S2. Describes assessment of bias by included study.Additional file 2: Figure S1. Describes study sites. Figure S2. Describes the relationship between haemoglobin on enrolment and continuous covariates. Figure S3. Describes the relationship between the predicted probability of moderately severe anaemia on day 3 and continuous covariates. Figure S4. Describes the relationship between the predicted probability of a large fractional fall in haemoglobin on day 7 and continuous covariates.Additional file 3: Table S3. Describes the overview of antimalarial treatments. Table S4. Describes the risk factors for moderately severe anaemia at enrolment (univariable logistic regression). Table S5. Describes the risk factors for moderately severe anaemia at enrolment (multivariable logistic regression). Table S6. Describes the risk factors for moderately severe anaemia at day 7 (univariable logistic regression). Table S7. Describes the risk factors for moderately severe anaemia at day 3 (univariable logistic regression). Table S8. Describes the risk factors for moderately severe anaemia at day 3 (multivariable logistic regression). Table S9. Describes the risk factors for a large fractional fall in haemoglobin by day 7. Table S10. Describes the sensitivity analysis for risk factors for moderately severe anaemia at enrolment (multivariable logistic regression). Table S11. Describes the sensitivity analysis for risk factors for moderately severe anaemia at day 7 (multivariable logistic regression).


Background and Objective: Dengue has emerged globally as the most relevant viral infection transmitted by a mosquito bite and represents a major threat to public health. Dengue-related renal manifestations such as proteinuria, hematuria, acute kidney injury (AKI), and rhabdomyolysis are not uncommon, and acute kidney injury (AKI) is a serious complication of dengue fever. There is relatively few data on the renal manifestations of dengue fever in children. Hence, this study was conducted to evaluate the incidence, characteristics, and clinical outcome of dengue fever with renal manifestations. Method. This prospective cross sectional study was conducted in Dr. M R Khan Children Hospital and Institute of Child Health, Dhaka, over a period of 1 year from January 2018 to December 2018. The study was approved by the ethical committee of the institute. A total number of 316 patients were admitted with the diagnosis of dengue fever either NS1 positive or antibody IgM positive or both IgM and IgG positive. Data were collected in a structured questionnaire form and were analyzed by SPSS version 20.0. The disease severity was classified according to the World Health Organization criteria. Renal manifestations were divided into AKI groups using pRIFLE criteria. Proteinuria was defined as urinary protein >1+ (30 mg/dL) by dipstick test. Hematuria was defined as red blood cell (RBC) >5/μL in a fresh uncentrifuged urine specimen. Result. Among 316 dengue patients, thirty-one patients (9.8%) had renal involvement. Most of the patients (54.83%) with renal manifestations were aged between 1 and 5 years. A total of 14 patients were found to have proteinuria (4.4%). Nephrotic-range proteinuria was seen in only one patient (0.3%). AKI was defined by pRIFLE criteria and was seen in 13 patients (4.1%); among AKI 6 (46.15%) had risk, three patients (23.07%) had injury and 4 (30.7%) had failure and needed peritoneal dialysis. Death occurred in 3 patients (9.6%) in dengue with AKI who had failure. The incidence of renal manifestations  is as high as 9.8% among patients with dengue, and those with AKI had significant morbidity and mortality. Conclusion. Renal involvement in children with dengue is not uncommon. Dengue associated with AKI had significant mortality and morbidity. Aedes aegypti is the primary mosquito vector; however, other species from the genus Aedes, such as Aedes albopictus, can also be vector of dengue virus transmission [Dengue infection has been identified as the fastest spreading mosquito-borne viral disease by World Health Organization . It is asmission .Incubation period of dengue virus infection is 3–14 days with a variety of clinical manifestation including asymptomatic infection, undifferentiated fever, dengue fever (DF), dengue hemorrhagic fever (DHF), and life-threatening dengue shock syndrome (DSS) . SimilarThis prospective cross sectional study was conducted in Dr. M R Khan Children Hospital and Institute of Child Health over a period of 1 year from January 2018 to December 2018. The study was approved by the ethical committee of the institute. All patients aged 6 months to 13 years who met the WHO criteria of dengue fever, i.e., clinical feature plus either NS1 positive or dengue IgM positive or both Dengue IgM and IgG positive patients were included in this study. Patients who did not give consent, who have preexisting renal disease were excluded from this study.μL in a fresh uncentrifuged urine specimen. All patients were managed by hospital protocol and investigation was sent according to patient's condition and management protocol. So, we sent routine tests as well as electrolyte to see hematological and electrolyte changes among dengue patients for treatment purpose. These parameters also help for early identification of complications in study group.The disease severity was classified according to the World Health Organization criteria. The renal manifestations were divided into AKI and non-AKI groups using pRIFLE criteria which are described as follows. Proteinuria was defined as urinary protein >1+ (30 mg/dL) by dipstick test. Hematuria was defined as red blood cell (RBC) >5/For patients who had AKI with failure, peritoneal dialysis was initiated. Patients who need ICU support were shifted to ICU. Among the patient who had proteinuria and hematuria, none underwent renal biopsy at the time of diagnosis. They followed-up monthly for 3 months for any persisted significant proteinuria and hematuria for further biopsy plan. But no significant proteinuria or hematuria was found in any patient .Among 316 dengue patients thirty-one patients (9.8%) had renal involvement. Among renal involvement, 14 patients (45.10%) had proteinuria, 13 (42%) had AKI, and 4 (12.90%) patients had hematuria . Among 4In dengue fever, only 3 (1.4%) patients were found to have renal involvement, whereas dengue shock syndrome and dengue hemorrhagic fever had highest renal involvement 35.8% and (17.9%), respectively .P value <0.001) and mean hematocrit level is also significantly higher in the renal group (41.49 ± 4.47) than in patients without renal manifestation (39.98 ± 5.16) . Serum Na+, serum K+, and platelet and leukocyte changes are not significant between two group.Among 13 patients with AKI in children with dengue fever, mostly 46.15% had risk, 30.76% had failure requiring peritoneal dialysis, and 23.07% had only injury managed conservatively .The duration of hospital stay in patients with AKI was 6 ± 2 days in risk group, 7 ± 5 days in injury, and 11 ± 2 days in patients with failure group. Recovery of renal function was seen in all patients with pRIFLE risk and injury group and one patient with failure group .13 patients were found with AKI according to the pRIFLE criteria; out of 13 patients, 4 patients were in failure/had failure and required peritoneal dialysis. Three of them died. Among this 3 deaths, 2 had platelet count <50,000 and 1 had platelet count 50,000–100,000. The cause of death was multiorgan failure. Among these 3 deaths the duration of PD was 48–72 hours. One patient out of 4 patients with failure was recovered fully, and duration of dialysis was 72 hours.Among thirty-one patients of renal involvement, 14 patients (45.10%) had proteinuria, 13 (42%) had AKI, and 4 (12.90%) patients had hematuria.In dengue fever, only 3 (1.4%) patients were found to have renal involvement, whereas dengue shock syndrome and dengue hemorrhagic fever had highest renal involvement 35.8% and 17.9%, respectively.P value <0.001), and hematocrit level is significantly higher in the renal group than in patients without renal manifestation . Serum Na+, serum K+, and platelet and leukocyte changes are not significant.Among 14 patients with proteinuria 7 (50%) had mild proteinuria, 3 (21.4%) had moderate, 3 (21.4%) patients had severe proteinuria, and only one patient (7%) had nephrotic range of proteinuria.Among thirty-one patients with renal involvement majority, 19 had platelet count<50,000 with high mortality (2 patients died). Another patient died whose platelet count was 50,000–100,000. Mortality was zero when platelet was more than 100,000.The duration of hospital stay in patients with AKI was 6 ± 2 days in the risk group, 7 ± 5 days in injury, and 11 ± 2 days in patients with the failure group. Recovery of renal function was seen in all patients with pRIFLE risk and injury group and one patient with failure group.Dengue fever can be presented with variety of clinical presentation with unpredictable progression and outcomes. Its presentation ranges from asymptomatic forms to severe shock, eventually resulting in death .Dengue infection has been associated with various renal disorders. Acute renal failure, proteinuria, hematuria, and glomerulonephritis have been reported during or shortly after acute dengue infection. In our study, among 316 dengue patients, thirty-one patients (9.8%) had renal involvement. Eswarappa et al.'s retrospective study showed prevalence of renal manifestation in dengue fever is 9.02% of the study population, which is similar to our study .In this study, thirty-one patients of renal involvement majority (45.10%) had proteinuria. Among 14 patients with proteinuria mostly (50%) had mild proteinuria, 3 (21.4%) had moderate 3 (21.4%) patient had severe proteinuria, and only one pt had nephrotic range of proteinuria. Similar findings found in Horvath et al., where proteinuria in 74% of patient in whom urinalysis was performed during a dengue-3 epidemic in Queensland, Australia . In this3; the prevalence of proteinuria in this cohort was 30% [Whereas in our study, prevalence of proteinuria was 45.01%, and Garcia et al. retrospectively studied 74 patients with dengue fever or DHF who had a platelet count of less than 125,000/mm was 30% . This wiIn the present study, 13 patients (42%) who had AKI in children with dengue fever mostly (46.15%) had risk, 30.76% had failure requiring peritoneal dialysis, and 23.07% had only injury managed conservatively.The reported frequency of AKI in dengue fever association exhibits wide variation in accordance with the particular population being assessed, severity of dengue, criteria used for the diagnosis of AKI, and time of evaluation. Laoprasopwattana et al.  reportedIn our study, 4 (12.90%) patients had hematuria which is similar to the study by Lizarraga et al, where both studies hematuria has been reported in up to 12.5% of patients with DHF , 21In dengue fever, only 3 (1.4%) patients were found to have renal involvement, whereas dengue shock syndrome and dengue hemorrhagic fever had highest renal involvement of 35.8% and 17.9%, respectively. These findings correlate with another study by Guzman et al. where they found dengue shock syndrome had the highest percentage (37.5%) of renal involvement .Among thirty-one patients with renal involvement, 19 had platelet count<50,000 with high mortality (2 patients died). Another patient died whose platelet count was 50,000–100,000. Mortality was zero when platelet was more than 100,000.P value <0.001), and hematocrit level is also significantly higher in the renal group (41.49 ± 4.47) than in patients without renal manifestation (39.98 ± 5.16) . Serum Na+, serum K+, and platelet and leukocyte changes are not significant. Tauqeer et al. showed same findings in a retrospective study. They also found hematocrit rises significantly in AKI with dengue fever group than non-AKI dengue fever [3) and relative lymphocytosis (60–80%) and in severe dengue, intense thrombocytopenia and increased hematocrit values. In addition, the patients might exhibit abnormal results on the coagulation tests, increased urea and creatinine levels, low complement component 3 (C3) levels, and alterations in urinalysis results  [In this study, mean serum creatinine (micromole/L) is significantly higher in patients with dengue fever (185.17 ± 121.35) with renal involvement vs. patients without renal involvement (85.50 ± 16.99) (ue fever . In anotcyturia) .The duration of hospital stay in patients with AKI was 6 ± 2 days in the risk group, 7 ± 5 days in injury, and 11 ± 2 days in patients with failure group. Recovery of renal function was seen in all patients with pRIFLE risk and injury group and one patient with failure group.Retrospective studies of case series of dengue have shown that the development of AKI was associated with a longer hospital stay and higher mortality , 24–26 wAmong 13 patients with AKI, 4 patients were in failure, 3 of them died, 2 had platelet count <50,000, and one had platelet count 50,000–10000. The cause of death was multiorgan failure. In a retrospective series, 60% of hospitalized DHF patients with ARF died. DHF patients with ARF were predominantly older men and had other comorbidities. Multivariate analysis showed that DSS was an independent risk factor for the development of ARF in patients with DHF .Dengue fever is associated with a variety of renal disorders. Acute renal failure is a serious complication of dengue fever and carries a high mortality rate. Transient proteinuria and hematuria has been detected in most patients with dengue fever. These findings will draw an attention to the need for clinicians' alertness to this renal complication of dengue fever in children. Adequate knowledge of clinical profile and predictors of AKI development would help in early intervention to prevent complication of renal involvement in children with dengue fever.


The effectiveness of Severe Acute Respiratory Syndrome Coronavirus 2 vaccines after two doses needs to be demonstrated beyond clinical trials.In a retrospective cohort assembled from a cross-institution comprehensive data repository, established patients of the health care system were categorized as having received no doses, one dose or two doses of SARS-CoV-2 mRNA vaccine through April 4, 2021. Outcomes were COVID-19 related hospitalization and death.Of 94,018 patients 27.7% had completed two doses and 3.1% had completed one dose of a COVID-19 mRNA vaccine. The two dose group was older with more comorbidities. 1.0% of the two dose group had a COVID-19 hospitalization, compared to 4.0% and 2.7% in the one dose and no dose groups respectively. The adjusted Cox proportional-hazards model based vaccine effectiveness after two doses (vs. no dose) was 96%:95–97), compared to 78%(95%CI:76–82) after one dose. After two doses, vaccine effectiveness for COVID-19 mortality was 97.9%(95%CI:91.7–99.5), and 53.5%(95%CI:0.28–80.8) after one dose. Vaccine effectiveness at preventing hospitalization was conserved across age, race, ethnicity, Area Deprivation Index and Charlson Comorbidity Indices. Cohort Enrollment and Distribution by Immunization Status and Vaccine effectiveness against mortalityCohort members are described by their immunization status and hospitalization at the end of the study period ending April 4th, 2021. Percentages compare this population to the total established patients. Each group is then divided into when hospitalized events occurred across immunization status. These percentages compare the number of events to the population in the immunization status at the end of the analysis period. Odds ratios for mortality were calculated and vaccine effectiveness calculated as 1 minus odds ratio times 100%.In a large, diverse US cohort, receipt of two doses of an mRNA vaccine was highly effective in the real-world at preventing COVID-19 related hospitalizations and deaths with a substantive difference in effectiveness between one and two doses.All Authors: No reported disclosures


At the end of the experimental period, six lambs randomly chosen from each treatment were slaughtered to determine the carcass traits and meat quality. Results showed that most carcass and meat traits were affected by diets. Average daily gain (ADG) was higher (P < 0.001) for T3 (158 g/day) than T2 (120 g/day) and T1 (118 g/day). Hot carcass weight (HCW) was higher (P < 0.001) for T3 (19.50 kg) than T2 (17.43 kg) and T1 (17.20 kg). Meat pH (5.43–5.56) and drip loss (3.03–3.23%) were similar (P > 0.05) among all treatments. Meat from animals in T3 (33.97 L∗) was lighter (P < 0.001) than T2 (30.75 L∗) and T1 (29.43 L∗). Shear force and cooking loss were greater (P < 0.05) for T1 (42.6 N and 26.12%) than T2 (40.4 N and 24.39%) and T3 (40.7 N and 24.18%). No variation was seen in meat moisture, protein and ash contents (P > 0.05) while intramuscular fat was higher in T3 (4.18%) than T2 (3.87%) and T1 (3.79%) (P < 0.01). The study indicated that carcass traits and meat quality could be modulated through dietary manipulation.This study was conducted to evaluate slaughter performance and meat quality of Begait sheep breed reared under different feeding options. Thirty intact fattening lambs (32.81 ± 2.39 kg) were used in randomized completely block design with three dietary treatments in ten replicates for a 90 day feeding trial. Dietary treatments constituted grass hay fed  Carcass traits, Lamb feeding, Meat quality, Sheep. The livestock sector plays a considerable role in poverty reduction, national income growth, exports and foreign exchange earnings, in achieving better food security and contribute to climate mitigation and adaptation . About 3The major feed bases of sheep in Ethiopia are natural pasture, grass hay and crop residues . NutritiThere is a need to significantly enhance livestock production and productivity to meet the ever-increasing demand for livestock products . This calls for planned supplementation of the roughage-based livestock to overcome the inadequate problem of feed and improve productivity through formulating an optimum balanced diet. In the tropics, crude protein has been recognized as the most limiting nutrient during dry seasons. Supplementation of dietary is known to enhance intake by increasing the supply of nitrogen to the rumen microbes. This has a positive effect in increasing rumen microbial population and efficiency, thus allowing them to enhance the degree of breakdown of the digesta. As the degree of digesta breakdown increases, feed intake also increased .In the study area, the most available and affordable plant protein source ingredients for smallholder livestock producers are sesame seed cake, cotton seed cake and noug seed cake. In spite of the availability of these agro-industrial by-products in the study area, smallholder farmers are not effectively utilized by for feeding. This is mainly due to lack of information and practice. However, the use of these by-products is a potential option through which the productivity of animals can be enhanced. Thus, supplementing sheep with protein source concentrate which are less competitive in human food system is commendable.Begait sheep breed is one of the identified indigenous Ethiopian sheep breeds located in the western zone of Tigray with promising production and reproduction potential, resulting in high litter size, early maturity, short lambing interval, and high milk yield . Despite22.1The experiment was conducted at the small ruminant research unit of Humera Agricultural Research Center, Northern Ethiopia. The experimental site is located at 14° 15′ N latitude and 36° 37′ E longitude at an altitude of 608.9 m above sea level. The area receives an annual rainfall ranging from 400 to 650 mm. The annual temperature of the area ranges from 22.2 to 42 °C. The climatic condition of the area is hot and semi-arid with a uni-modal rainfall pattern .2.1.1The experiment was approved (19641ET-27/2020) by the Ethics Committee of the Tigray Agricultural Research Institute following guidelines of the European Union directive number 2010/63/2.2Thirty vaccinated and dewormed yearling intact growing male Begait lambs (32.81 ± 2.39kg) were sourced from near sheep farm to the study area. The lambs were kept for 90 days, which were preceded by 15 days of acclimation to the new facilities and diets with the considering of animal welfare.ad libitum common to all groups and supplemented with a mixed diet of 48% wheat bran (wb), 15% molasses, 35% cottonseed cake (csc), 1% salt and 1% limestone (T1); 43% wb, 20% sorghum grain, 35% noug seed cake(nsc), 1% salt and 1% limestone (T2) and 47% wb, 16% molasses, 35% sesame seed cake (ssc), 1% salt and 1% limestone (T3). The experimental treatments were chosen for their availability and potential utilization in the study area. The diet was offered with a grass hay and concentrate, targeting for a weight gain of 200 g/day following the ad libitum access to natural grass hay and free water.The animals were blocked according to their initial body weight which was determined by taking the mean of two consecutive weightings after overnight fasting for water and feed. They were grouped into ten blocks of three animals each based on initial body weight. The three treatment diets were randomly assigned to each experimental animal. Each animal within the block got an equal chance of receiving one of the treatment diets. The experimental diets were consisted of grass hay fed 2.32.3.1Feed offered and refused was recorded daily and daily feed intake was calculated as the differences between offer and refusal. Representative feed samples were collected and stored for each experimental animal and pooled over the feeding trial period for further chemical analysis. Each lamb was weighed at the beginning of the experimental period and every 10 days interval throughout the experiment after overnight fasting at 6:00 AM before daily feed offering to avoid feed effect. To obtained average daily gain (gram/day), initial live weight of the animal was subtracted from final live weight and then divided by the number of feeding days.2.3.2At the end of the experimental period, eighteen randomly selected lambs (six from each dietary treatment) were transported to the Abergelle International Export Abattoir, Mekelle, Ethiopia and rested for 3 days in covered yards to avoid stress. Prior to slaughter, lambs were fasted for 16 h from the feed with free access to water. Animals were slaughtered according to the standard commercial procedures after recording weight just before slaughter to obtain the slaughter body weight (SBW).Skin, head, forefeet, hind feet and all the viscera and fat depots  were removed to determine the hot carcass weight (HCW). Gut fat comprised omental and mesenteric fat. The dressing percentage (DP) was obtained as the proportion of HCW to SBW (DP = HCW∗100/SBW) as defined by 2.3.32) was measured by making a transverse section between the 13th thoracic and first lumbar vertebrae, thereby exposing the transverse section of the rib from the right half carcass after chilled at 4 °C overnight. The Rib-eye area was measured using a grid sheet for transparency tracing as described by th and 12th rib bone for sub-sectioning and further meat physicochemical analysis. The right LL was used for determination of pH, color, drip loss, cooking loss, and shear force while the left side samples were reserved for the determination of chemical composition. After taking the color measurements, the same steaks previously used for meat color measurements were vacuum packaged and aged for 7 days in chilling temperature (4 °C). After seven days of aging, steaks were placed in a frozen (-20 °C) until cooking loss and shear force analysis were performed. The day before the analyses, the frozen steaks of LL were thawed overnight at 4 °C. After thawing, steaks were subjected for subsequent measurement of cooking loss and shear force at the meat Laboratory unit of Hawassa University, Southern Ethiopia.Carcasses were chilled to the cold room, with an average temperature of 4 °C, where they remained for 24 h hanging from hooks by the tendon of the gastrocnemius muscle. After carcasses were chilled, carcasses were taken from the cooling chambers and weighed again to determine the cold carcass weight (CCW) and chilling losses were determined as follows: Chilling losses (%) = [(Hot carcass weight - Cold carcass weight)/Hot carcass weight ]∗100. Rib-eye area ) having a sharp penetrating blade over the electrode, as described by The pH values of the LL were measured at approximately 24 h (pH24) 2.3.3.2Meat color measurement was performed on steaks of LL muscle 24 h after chilling at 4 °C. Steaks were exposed on a flat surface of white background in the measuring room and allowed to air 30 min prior measurements. Spectrophotometer was set to the L∗ (lightness), a∗ (redness), and b∗ (yellowness) system using illuminate D65, an observer angle of 10°, with an aperture size of 5.0 mm. Values of L∗, a∗, and b∗ were recorded from three readings performed at different points on the surface of each steak, using a HunterLab MiniScan EZ spectrophotometer  calibrated with black and white standardized plates between measurements .2.3.3.3To determine drip loss, the ‘EZ’ method following the protocol adapted by 2.3.3.4Steaks with 2.5 cm thickness were removed from each aged LL and weighed accurately (pre-cooked weigh), vacuum packaged and then frozen at -20 °C. The day before cooking, frozen steaks were thawed in refrigerator at 4 °C. Then the sample was immersed in a 72 °C water bath for 35 min in plastic bags, following which they were immediately cooled in cold tap water for 30 min. After cooling, samples were then removed from the bags, wiped with filter paper and then reweighed again (post-cooked weigh), calculated as the cooking loss (%) = [(pre-cooked weight – post-cooked weight)/pre-cooked ] ∗ 100 as described by .2.3.3.5The cooked meat samples were then refrigerated overnight and were then subjected to the measurement of shear force using a GR texture analyzer  with a V-shaped Warner-Bratzler shear force, blade, operating at a constant speed of 225 mm/min. Shear force was calculated as the average of 6 subsamples . In brie2.3.3.6Evaluation of meat chemical composition  was performed according to the methods described by the Association of Official Analytical Chemists , at the 2.3.3.7Partial budget analysis was done according the procedure of 2.4Data on carcass and meat qualities were subjected to analyses of variance (ANOVA) according to a randomized complete block design using the General Linear Models (GLM) procedure of SAS version 9.3 . Signifi33.1P < 0.05). Similarly, lambs supplemented with T3 ration had significantly (P < 0.001) higher ADG (158.6 g/day) than in T2 (120 g/day) and T1 (118 g/day). Lambs fattened under T3 had higher FCE (ADG: daily DM intake) than T1 and T2.3.2P > 0.05).Slaughter performance is directly related to the economic importance of meat animals. The results of slaughter traits for Begait lambs kept under different feeding regimes are given in 2) than that of lamb in T2 (13.50 cm2) and T1 (13.37cm2). Similarly, fat thickness showed significant difference (P < 0.001) among the diets (Rib-eye area was influenced by the dietary treatments and higher for lambs receiving T3 (16.12 cmhe diets . Highest3.3P > 0.05). IMF was significantly modulated by treatment rations (P < 0.05). Intramuscular fat (IMF) was higher in the LL from lambs fed on diets supplemented with T3 than those lambs supplemented with T2 and T1.As shown in P > 0.05) among the dietary groups. Coming to the meat color, L∗ in T3 (33.97) was recorded higher (P < 0.001), but no difference was observed between T1 (29.43) and T2 (30.75) (P > 0.05). Regarding the other two-color indexes (a∗ and b∗), there were quite similar (P > 0.05) among treatment groups, and a∗ values at 24 h ranged from 9.99 to 10.99. Dietary treatment had no significant effect (P > 0.05) on the drip loss percentage, which ranged between 3.03% and 3.32%. Cooking loss was significantly dictated by dietary treatments (P < 0.05). Meat sampled from sheep kept under T1 (26.12%) had higher cooking loss compared to meat sampled from sheep that received T2 (24.39%) and T3 (24.18%). Meat tenderness was significantly influenced by diets (P < 0.05). The measured WBSF (Newton) was significantly lower in T2 (40.40) and T3 (40.60) dietary groups compared to T1 (42.60) group diets. No significant difference (P > 0.05) was observed between T2 and T3 dietary groups in shear force (meat tenderness).The technological meat quality characteristics of LL of Begait lambs fed under different treatments are presented in 3.4The partial budget analysis of Begait lambs fed under different treatments are presented in 44.1The higher DM intake observed in T3 in the present study could be associated with increased protein intake that contribute more nitrogen supply to the rumen microorganisms . This coFCE value observed in this study was consistent with the trend of ADG for all treatments. In agreement to the present study, 4.2Differences among treatments in hot carcass weight and rib eye area observed in this study were consistent with dressing percentage. The higher carcass weight recorded in T3 reflects that higher feed consumption enhanced muscle growth. Indeed, the recorded HCW of Begait lamb (17.20–19.50 kg) in the current study was superior to the entire carcass weight of Ethiopian indigenous sheep breeds reported previously in the literature by Carcass chilling loss was not affected by diets. Chilling losses (2.13–2.39%) were lower than results 4.08–4.2% and 4.36–5.7% reported by 2) obtained in this study were higher than the value (5.71–9.20 cm2) for Horro, Washera, Afar, and Arsi-Bale lambs reported by different researchers  were within the acceptable range for the export-import market, revealing the glycogen levels in the muscle of the meat was high enough to build up the optimum level of lactic acid causing a fall in pH and thereby improving the shelf life of the meat . Hence, The higher L∗ value in T3 group diets could be due to the attribution of more intramuscular fat content that makes the meat luminous . In agreIn the present study, drip loss was not modulated by dietary treatment. This result did not agree with those of Cooking loss was affected by diets with higher for meat sampled from lambs fed on T1 as compared to meat from the other two diets. Differences in intramuscular fat content  could paMeat tenderness was significantly affected by diets and tender (less shear force) was recorded for meat samples from lambs fed in T3 as compared to lambs in diets T2 and T1. Meat with low shear force tends to have good tenderness and vice versa. The relatively less shear force of T3 could be attributed to a combination of factors that involve higher intramuscular fat and water holding capacity as explained by 4.4The difference in the net return and rate return among dietary treatment groups were due to the quality feed perform, better feed conversion efficiency, body weight gain of the lambs, and difference in feed cost and selling price of the animals. The partial budget analysis also demonstrated that T3 had higher net return and rate return due to higher body weight gain (158.62 g/day) as compared to the other treatments that had relative body weight gain of 120.37 g/day and 118.25 g/day for T1 and T2 respectively. Therefore, T3 was better as compared to the other feeding options. However, the use of either diet depends on the availability and cost of feed ingredients.5The current study showed that growth, carcass and meat characteristics of fattening Begait lambs are affected by diet. A diet composed of 16% molasses, 47% wb, 35% ssc, 1% salt and 1% limestone gave better biological performance and economic return. This implies that feeding of Begait lamb with dietary treatment 3 is a better option for the production of heavy carcasses yield with superior quality of meat as compared to the other tested diets. However, the producer may choose one of the diets depending on the availability and cost of feed ingredients to maximize the performance of feedlot lambs. Future research is also warranted to explore the effects of this feeding regime on fatty acid composition and consumer acceptability meat of fattening Begait lambs to complement the results obtained in this study.Kahsu Atsbha: Performed the experiments; Analyzed and interpreted the data; Wrote the paper.Tikabo Gebremariam: Conceived and designed the experiments; Wrote the paper.Teferi Aregawi: Contributed reagents, materials, analysis tools or data; Wrote the paper.Tigray Agricultural Research Institute and Humera Agricultural Research Center.This work was supported by Data associated with this study has been deposited at Kahsu.The authors declare no conflict of interest.No additional information is available for this paper.


However, few studies have examined the adverse effects of PM2.5 based on an entire population of a megalopolis. In addition, most studies in China have used averaged data, which results in variations between monitoring and personal exposure values, creating an inherent and unavoidable type of measurement error.Positive associations between ambient PM2.5 exposure. Time-stratified case-crossover design and conditional logistic regression models were adopted to estimate cardiorespiratory hospitalization risks associated with short-term exposure to PM2.5. We also conducted stratification analyses by age, sex, and season.This study was conducted in Wuhan, a megacity in central China with about 10.9 million people. Daily hospital admission records, from October 2016 to December 2018, were obtained from the Wuhan Information center of Health and Family Planning, which administrates all hospitals in Wuhan. Daily air pollution concentrations and weather variables in Wuhan during the study period were collected. We developed a land use regression model (LUR) to assess individual PM2.5 was associated with an increased risk of a cardiorespiratory hospital admission. A 10 μg/m3 increase in PM2.5 (lag0–2 days) was associated with an increase in hospital admissions of 1.23% (95% CI 1.01–1.45%) and 1.95% (95% CI 1.63–2.27%) for cardiovascular and respiratory diseases, respectively. The elderly were at higher PM-induced risk. The associations appeared to be more evident in the cold season than in the warm season.A total of 2,806,115 hospital admissions records were collected during the study period, from which we identified 332,090 cardiovascular disease admissions and 159,365 respiratory disease admissions. Short-term exposure to PM2.5 on cardiorespiratory hospital admissions, which may be helpful for air pollution control and disease prevention in Wuhan.This study contributes evidence of short-term effects of PMThe online version contains supplementary material available at 10.1186/s12931-021-01731-x. Numerouorbidity . Accordiorbidity .2.5 on cardiorespiratory diseases [2.5 and cardiorespiratory hospital admissions based on all citizens of a large city are needed to better understand the real impact of ambient fine particulate matter in China.Previous studies have provided strong evidence of the harmful effects of PMdiseases . Althougdiseases , 8, havediseases , 10. Howdiseases , 12, butExposure assessment methods are crucial for epidemiological studies. Commonly used air pollution assessment methods include monitoring data derived from fixed stations, Dispersion Models (DM), atmospheric Chemical Transport Models (CTMs), and Land Use Regression (LUR) , 14. Mos2.5 on the entire population can be assessed. Furthermore, LUR models were developed to better capture individual PM2.5 exposure. The objective of this analysis was to examine the association between PM2.5 and cardiorespiratory hospital admissions.Therefore, this study was conducted based on the admission data of all hospitals in Wuhan, from October 2016 to December 2018. Considering Wuhan’s universal access to hospital healthcare and the availability of these records, the impact of PM2 and a population of about 10.9 million , Wuhan (29.58°N to 31.22°N and 113.41°E to 115.05°E) is the capital city of Hubei Province and a megacity in central China. Due to its subtropical, monsoon climate, Wuhan has typical weather featured in distinct seasons and abundant rainfall. The major sources of air pollution in the city are biomass and coal combustion, steel manufacture, smelting, and vehicle emissions [With a land area of 8569.15 kmhttp://wjw.wuhan.gov.cn/) between Oct 1, 2016 and Dec 31, 2018. The Wuhan Information center of Health and Family Planning is a hospital authority within the municipal Bureau of Health, to which all the hospitals in Wuhan have to report their information of hospital infrastructure, medical service and management. All of the public hospitals , a total of 59 municipal hospitals, were included in this study. From each record, we extracted de-identified patient age, sex, home address, and primary diagnosis. The diagnoses were made by licensed specialized physicians according to current clinical guidelines. Cardiorespiratory hospital admissions in the present study were identified based on the primary diagnosis according to the International Classification of Diseases, 10th Revision (ICD-10): total cardiovascular disease , hypertension (I10–I15), coronary heart disease , stroke (I60–I69), total respiratory disease (J00–J99), and chronic obstructive pulmonary disease . A total of 2,806,115 hospital admission records were collected during the study period, from which we identified 332,090 for total cardiovascular diseases and 159,365 for total respiratory diseases. Specific inclusion and exclusion criteria are outlined in Additional file Daily hospitalization records were obtained from the Wuhan Information center of Health and Family Planning (http://hbj.wuhan.gov.cn/), which has established 20 ambient air quality monitoring stations in the 13 districts of Wuhan city. To calculate daily 24-h concentrations, ≥ 75% of the 1-h values must have been available on that particular day; To calculate the annual concentration, there must be at least 324 daily values available. Four stations were excluded because the above criteria were not met. Finally, daily 24-h average concentration data for PM2.5 , sulfur dioxide (SO2) , nitrogen dioxide (NO2) , and carbon monoxide (CO)  during the study period were collected from 16 air quality monitoring stations .During the study period, the air pollution data were collected from the Wuhan Environmental Protection Bureau  design was first proposed by Maclure  to study2.5 exposures and cardiorespiratory hospital admissions in Wuhan. The case day was defined as the day of hospital admission and the control days were identified by matching the day of the week (DOW) within the same year and month. By virtue of this design, the potential confounding effects of long-term trends and seasonality can be largely eliminated.In this study, we performed a time-stratified case-crossover study design to evaluate associations between short-term PM2.5 exposures on cardiorespiratory hospital admissions. To control covariates, we applied a natural cubic spline (NCS) function with 3 degrees of freedom (df) for both temperature and humidity to eliminate nonlinear confounding effects.We used a conditional logistic regression (CLR) model to obtain estimates of the odds ratios (ORs) and 95% confidence intervals (CIs) for the effect of PM2.5 and cardiorespiratory admissions was further checked by smoothing the PM2.5 terms using the NCS function (with 3 df).Considering that a single-day lag model might underestimate the association , the cum2.5 and cause-specific hospital admissions deriving from the single pollutant model. The Z-test was applied to test the statistical significance of differences by gender or season [Furthermore, we conducted stratification analyses by age , sex , and season  to explore the potential effect modifiers on the associations between PMr season .2, SO2, CO) collected from the monitoring stations closest to patients’ homes; (2) conducting a symmetric CCO design  [To check the robustness of our main results, we conducted several sensitivity analyses by: (1) fitting two-pollutant models by additionally adjusting for air pollutants  ; and (3)3 increase in PM2.5 concentrations.All of the analyses were conducted using R, version 3.5.1. We used the “survival” package for CLR analysis. Two-sided tests were conducted, and effects with p < 0.05 were considered to be statistically significant. All results of model estimates are reported as ORs and 95% confidence intervals (CIs) associated with each 10 μg/mA total of 491,455 hospital admissions, of which 332,090 were for total cardiovascular diseases and 159,365 for total respiratory diseases, were recorded from October 1, 2016 to December 31, 2018 in Wuhan , but it exceeded the World Health Organization (WHO) air quality guidelines (AQG).During the study period, the mean daily average concentrations were 48.2 μg/m2.5 showed similar lag patterns for it’s impact on total cardiorespiratory hospital admissions  increment in daily hospital admissions for total CVD and a 2.0% (95% CI 1.6%–2.3%) increment for total respiratory diseases . However, the hazard effects among people aged > 74 years were slightly lower than that of people aged 65–74 years in some cause-specific diseases . In addition, COPD patients aged 45–54 years were at the greatest risk, with ORs of 1.042 (95% CI 1.010–1.075)  and a sharper response at higher concentrations.There was a clear dose–response relationship between PM2.5 with a three-day moving average (lag0–2) in two-pollutant models were summarized in Table 2, SO2 and CO). Overall, the effects of PM2.5 remained stable after adjusting for gaseous pollutants for total cardiorespiratory diseases, while the effect estimates of PM2.5 in two-pollutant model were slightly smaller than in single-pollutant model. Notably, for three gaseous pollutants, the adverse effects were observed on most cardiorespiratory diseases after adjusting for PM2.5.The risk estimates of PM2.5 on hospital admissions based on an entire population of a megalopolis using LUR models. Evidence gained in this study showed a significant PM2.5-associated risk on cardiovascular diseases  and respiratory diseases (including COPD), with robust outcomes after adjustment for other gaseous pollutants. Regarding subgroup analyses, the relationship estimates of different age groups varied from each other, while risk estimates were higher in the cold season. These findings provide strong evidence of associations between ambient PM2.5 and cardiorespiratory hospital admissions in Wuhan, and might help public agencies to develop strategies for air pollution control and disease prevention.To the best of our knowledge, this is the first study in China that has examined the adverse effects of PM2.5 was positively correlated with hospital admissions for respiratory illnesses. However, as PM2.5 concentrations in Wuhan were much higher, the magnitude of the risk estimates in our study was generally lower than in prior reports [2.5-related admission risk at lag2–5 in five European cities, in which a 12.4 μg/m3 increase in PM2.5 was associated with a 6.4% increase in respiratory hospital admissions [2.5 compositions and different lifestyle patterns are possible explanations.Our study found that short-term exposure to PM reports , 25. Onemissions . Individmissions . Second,2.5 exhibited a similar lagged pattern for overall cardiorespiratory admission as well as in different subgroups. For single-day lag models, the estimates for PM2.5 were the highest at lag0 day and decreased in later lag days, in line with previous studies [2.5 may increase the risk of hospital admission within hours of exposure. A multi-city study in England and Wales found an elevated risk for myocardial infarction by PM10 and NO2 at lag1–6 h, with excess risks of 1.2% (95% CI 0.3–2.1%) and 1.1% (95% CI 0.3–2.1%) respectively, per 10 μg/m3 increase [2.5 exposure were at lag0–5, for each 10 μg/m3 increment, associated with an increase of 4.31, 3.95, and 2.56% percentage change in the hospital admission rates for myocardial infarction, congestive heart failure, and ischemic stroke respectively [The lag effects of short-term exposure to air pollution are of wide interest in air pollution epidemiology. In this study, PM studies , 28. Thiincrease . Anotherincrease . In the increase . In New ectively . Conside2.5 and hospital admissions for respiratory and cardiovascular diseases. Similar to other studies, a higher susceptibility to PM2.5 was found among the elderly (over 65 years old). Such elderly high-risk association is widely accepted due to the weaker immune systems and potential for more chronic medical conditions. In addition, interesting deviations from this pattern were observed for specific subgroups of disease. The risk of COPD, coronary heart disease, and stroke in this study peaked in the middle-age group. For cause-specific cardiovascular diseases, CHD and stroke, the adverse effects were slightly higher in the 65–74 years group than in the over-74 years group. This result may be the consequence of a “harvesting effect” in which susceptible residents might have developed symptoms and died before reaching the age of 75 [3 increase in PM2.5 corresponding to a 4.25% (95% CI 1.02%–7.58%) increase in hospital admissions. This finding seems inconsistent to prior study results. In a cohort study conducted in the United States, a higher risk for hospital admission for COPD was found in age group ≥ 76 [This study explored the demographic-specific associations between PMge of 75 . Notablyoup ≥ 76 . More reoup ≥ 76 . The varoup ≥ 76 , 36, whi2.5-related hospitalizations for respiratory causes [The assessment of gender differences has been of wide interest in air pollution epidemiology. In the current study, although statistical significance of in gender difference was not observed for PM-associated risks for hospital admission, there were still slight deviations in the magnitude of risk estimates in males and females. For total respiratory disease, slightly higher risk estimates were found in females. For specific cardiovascular diseases, coronary heart disease and stroke, we found that males were at slightly higher risk for hospital admissions. Consistent with the results of the present study, a pooled analysis from 33 Chinese communities reported that the effect of ambient air pollution exposure on the prevalence of stroke and CVD was much higher in men than in women . Anothery causes . However2.5 on cardiorespiratory hospital admissions were found during the cold period. This may be due to the seasonal variation of PM2.5 in Wuhan, with a high concentration in winter and a lower one in summer  [In this study, higher short-term effects of PM spring) , 40.2.5 with total cardiovascular and respiratory diseases remained robust after adjustment for gaseous pollutants , suggesting PM2.5 seemingly has independent impact on total cardiorespiratory hospital admission. We also observed that the effect estimates of PM2.5 in two-pollutant model were slightly smaller than in single-pollutant model. In addition, after adjusting for PM2.5, gaseous pollutants themselves have an adverse impact on most cardiorespiratory diseases. Many studies have indicated similar results with this one [2.5 using single-pollutant models might be partly due to the exposure of gaseous pollutants, while the independent effect of gaseous pollutants has been proved [In two-pollutant analyses, the associations of PMthis one –43. Possn proved . However2.5 exposures and in detecting possible associations. This study has some limitations as well. First, we linked PM2.5 to cardiorespiratory diseases by date of hospital admission rather than by the date of symptom onset. This may have introduced a non-differential error in exposure measurement and underestimated the effect estimates. Second, while the exposure modeling methods employed in this study added new information in comparison with most previous studies, the deficiency of PM2.5 exposure data from occupation, commuting, and pollution originating from indoor sources may have further attenuated our effect estimates. Third, although the two-pollutant models were fitted to examine the robustness of the association between PM2.5 and hospital admissions, the collinearity between pollutants limited the ability to separate the independent effect of PM2.5.Compared with previous studies, this study has several strengths. First, we obtained hospitalization data from a total of 59 hospitals in Wuhan to evaluate the PM-admission relationships. Given Wuhan’s universal access to hospital health care, the potential for selection bias was minimized and the results can be directly generalized to the whole city. Second, the adoption of LUR model increases the accuracy when assessing the spatial variations in individual PM2.5 exposure as well as identifies sensitive subpopulations in Wuhan. We find that the cumulative effect of short-term PM2.5 exposure are higher than that of single day. The risk estimates of different age groups vary from each other, while the elderly are still at higher risk for most diseases. Besides, the higher PM-induced risk during the cold season cannot be ignored. These findings extend our knowledge related to the effects of higher levels of exposure and may help public agencies to develop strategies for air pollution control.This study provides evidence regarding the short-term health impacts of PMAdditional file 1:Figure S1. Flow chart of the selection process for the study population.Additional file 2:Table S1. Description of Developed LUR Models for PM2.5 in different year.Additional file 3:Table S2. Descriptive statistics of air pollutant concentration and meteorological factor in Wuhan, 2016.10 -2018.12.Additional file 4:Table S3. Spearman correlations among environmental variables in Wuhan, 2016.10 -2018.12.Additional file 5:Table S4. Odds ratio (95% CIs) of admissions at various exposure days, associated with per 10 μg/m3 increase of PM2.5.Additional file 6:Table S5. Odds ratio (95% CIs) of admissions at various exposure days, associated with per 10 μg/m3 increase of PM2.5, using symmetric CCO design.Additional file 7:Table S6. Sensitive analyses of odds ratio (95% CIs) of admissions at lag0~2 under varying degrees of freedom (df) for, associated with per 10 μg/m3 increase of PM2.5.Additional file 8:Table S7. Odds ratio (95% CIs) of cardiorespiratory hospital admissions stratified by age, gender and season, associated with per 10 μg/m3 increase of PM2.5.