The intestinal microbiota has been proposed to play a pathogenic role in coeliac disease (CD). Although antibiotics are common environmental factors with a profound impact on intestinal microbiota, data on antibiotic use as a risk factor for subsequent CD development are scarce.
Dengue Virus Disease: Recent Updates on Vaccine DevelopmentRSIS International
This paper reviews the current experimental updates made in the development of a dengue vaccine particularly DNA and plant derived vaccine. Dengue is an endemic viral disease affecting human health particularly children. Till today there is no medication or treatment available for dengue. Vector control measures are not yet successful in controlling dengue transmission. Introduction of Wolbachia bacteria might be the new ray of hope for the effective dengue vector control measures. The development of an efficient dengue vaccine is difficult because vaccine must be tetravalent so that it includes all the serotypes. Therefore, a tetravalent formulation plays an important role in developing a dengue vaccine. Recently tetravalent French dengue vaccine, Dengvaxia (CYD-TDV) (Sanofi Pasteur’s, France) available (limited to a few countries) on the market since 2015. Sanofi branded, Dengavaxia (CYD-TDV) is the most promising one and has recently successfully completed the phase III clinical efficacy trials in Asia and Latin America. Dengavaxia (CYD-TDV) has been shown to be safe and has different levels of efficacy against the four serotypes. However, DNA vaccination has not yet successful mainly due to the insufficient immunogenicity. Botanical dengue vaccine production is also safe and have many advantages but there are still challenges that limit the rate of successful production of plant expressed vaccines. There are numerous dengue vaccine candidates in pipeline but none of them not yet promoting vaccination.
Meta-Analysis Identifies Type I Interferon Response as Top Pathway Associated...CSCJournals
Background: Severe Acute Respiratory Syndrome (SARS) corona virus (CoV) infections are a serious public health threat because of their pandemic-causing potential. This work examines pathway signatures derived from mRNA expression data as a measure of differential pathway activity between SARS and mock infection using a meta-analysis approach to predict pathways associated with SARS infection that may have potential as therapeutic targets to preclude or overcome SARS infections. This work applied a GSEA-based, meta-analysis approach for analyzing pathway signatures from gene expression data to determine if such an approach would overcome FET limitations and identify more pathways associated with SARS infections than observed in our previous work using gene signatures...
Dengue Virus Disease: Recent Updates on Vaccine DevelopmentRSIS International
This paper reviews the current experimental updates made in the development of a dengue vaccine particularly DNA and plant derived vaccine. Dengue is an endemic viral disease affecting human health particularly children. Till today there is no medication or treatment available for dengue. Vector control measures are not yet successful in controlling dengue transmission. Introduction of Wolbachia bacteria might be the new ray of hope for the effective dengue vector control measures. The development of an efficient dengue vaccine is difficult because vaccine must be tetravalent so that it includes all the serotypes. Therefore, a tetravalent formulation plays an important role in developing a dengue vaccine. Recently tetravalent French dengue vaccine, Dengvaxia (CYD-TDV) (Sanofi Pasteur’s, France) available (limited to a few countries) on the market since 2015. Sanofi branded, Dengavaxia (CYD-TDV) is the most promising one and has recently successfully completed the phase III clinical efficacy trials in Asia and Latin America. Dengavaxia (CYD-TDV) has been shown to be safe and has different levels of efficacy against the four serotypes. However, DNA vaccination has not yet successful mainly due to the insufficient immunogenicity. Botanical dengue vaccine production is also safe and have many advantages but there are still challenges that limit the rate of successful production of plant expressed vaccines. There are numerous dengue vaccine candidates in pipeline but none of them not yet promoting vaccination.
Meta-Analysis Identifies Type I Interferon Response as Top Pathway Associated...CSCJournals
Background: Severe Acute Respiratory Syndrome (SARS) corona virus (CoV) infections are a serious public health threat because of their pandemic-causing potential. This work examines pathway signatures derived from mRNA expression data as a measure of differential pathway activity between SARS and mock infection using a meta-analysis approach to predict pathways associated with SARS infection that may have potential as therapeutic targets to preclude or overcome SARS infections. This work applied a GSEA-based, meta-analysis approach for analyzing pathway signatures from gene expression data to determine if such an approach would overcome FET limitations and identify more pathways associated with SARS infections than observed in our previous work using gene signatures...
Multidrugresistant tuberculosis
Among the most menacing forms of MDR is multidrug
resistant tuberculosis (MDR-TB). WHO estimates that
were about 450,000 new cases and 170,000 deaths from
MDR-TB in 2012. The number of cases reported to
WHO rose by an alarming 35% between 2011 and 2012,
although this probably mostly reflects increased recognition
and reporting. Over half the new cases were in India,
China or the Russian Federation.3
This issue of Homeopathy features a paper by Dr Kusum
Chand and colleagues reporting a randomized, double blind,
placebo-controlled clinical trial of individualized homeopathic
treatment or placebo in addition to standard antituberculous
chemotherapy as specified by the Indian Revised
National Tuberculosis Control Program, for MDR-TB
NON-STEROIDAL ANTI INFLAMMATORY DRUGS AND GASTROINTESTINAL TOXICITYApollo Hospitals
Non-steroidal anti inflammatory drugs (NSAIDs) because of their high efficacy as both anti-inflammatory and analgesic agents, are one of the most commonly prescribed drugs world-wide. They are used in treatment of many commonly occurring disorders such as chronic arthropathies, headache and low back pain. Their widespread and uncontrolled use is promoted by their over the counter availability. This acts as a double edge sword. One of the most common adverse effects that add largely to its morbidity and mortality
is the gastrointestinal tract damage.
Etiologia de la celulitis y Predicción clínica de la enfermedad Estreptocócic...Alex Castañeda-Sabogal
Etiologia de la celulitis. Estudio prospectivo y predicción clínica de la infeccion por Estreptococcus basado en la frecuencia encontrada de las especies de estreptococo
Convalescent Plasma and COVID-19: Ancient Therapy Re-emergedasclepiuspdfs
Convalescent plasma has again re-emerged as a therapy during coronavirus disease (COVID-19) outbreaks currently use as a prophylactic or an interventional treatment in infected patients. Convalescent plasma has been used in the 20th century confronting different infectious diseases where there was no other therapy available. Conceivably, this convalescent plasma therapy tends to be proving a game-changing treatment in some COVID-19 patients and could support treatment, in addition to the current interventions before other developed therapies are available for the population.
Prevalence of Chronic Kidney disease in Patients with Metabolic Syndrome in S...asclepiuspdfs
Background and Objective: Chronic kidney disease (CKD) which is an increasingly important clinical and public health issue is associated with cardiovascular disease. Epidemiologic studies have also linked metabolic syndrome (MetS) with an increased risk of incident CKD. Therefore, the present study was designed retrospectively to find the prevalence and potential risk factors of CKD in patients with MetS in Saudi Arabia.
A Study to Assess the Effectiveness of Planned Teaching Program on the Knowle...ijtsrd
Malnutrition and Tuberculosis chronic infectious disease are both problems of considerable magnitude in the most underdeveloped regions of the world. Malnutrition can leads to secondary immunodeficiency that increase the host susceptibility to infection. The aim of the study was to assess the effectiveness of planned teaching program on the knowledge and practice regarding dietary pattern among mothers of children with tuberculosis admitted in pediatric ward. Quasi experimental with two groups pre test post test design was used for 60 mothers at IPD and OPD of pediatric department and purposive sampling technique was used. Self structured questionnaire was used to assess knowledge and checklist for practice. In post test experimental group mothers have 63.3 average knowledge, 26.6 poor knowledge and 10 good knowledge while in the control group, 53.3 poor knowledge, 46.6 average knowledge and non hove good knowledge. In experimental group mean score was 17.9 1.96 while in control group mean score was 11.8 2.99. At the “p” value 0.05, the calculated t value 3.21 was compared with the tabulated value 2.01 . In post test experimental group, mothers have 53.3 good practice, 46.6 average practice and none have poor practice while in the control group, 63.33 average practice, 23.3 poor practice and 13.3 good practice. In experimental group mean score was 19.13 1.99 while in the control group, mean score was 14.06 2.85.At the “p” value 0.05, the calculated t value 3.28 was compared with the tabulated value 2.01 . These finding reveals that the planned teaching program on dietary pattern was effective. Mrs. Anchal Tiwari | Mrs. Anugrah Charan | Dr. Sarika Gupta "A Study to Assess the Effectiveness of Planned Teaching Program on the Knowledge and Practice Regarding Dietary Pattern among Mothers of Children with Tuberculosis Admitted in Pediatric Ward at KGMU Hospital, Lucknowv" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-2 , February 2021, URL: https://www.ijtsrd.com/papers/ijtsrd38591.pdf Paper Url: https://www.ijtsrd.com/medicine/nursing/38591/a-study-to-assess-the-effectiveness-of-planned-teaching-program-on-the-knowledge-and-practice-regarding-dietary-pattern-among-mothers-of-children-with-tuberculosis-admitted-in-pediatric-ward-at-kgmu-hospital-lucknowv/mrs-anchal-tiwari
Management of Helicobacter pylori infection in Greece: Current guidelines
4th Athens International Symposium on Digestive Diseases, Athens Greece 6-7 July 2018
Chris Zavos, MD, PhD, FEBGH
http://peptiko.gr
To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...YogeshIJTSRD
The severity and mortality of COVID 19 cases has been associated with the Three category such as vaccination status, severity of disease and outcome. Objective presently study was aimed to assess the severity and mortality among covid 19 patients. Methods Using simple lottery random method 100 samples were selected. From these 100 patients, 50 patients were randomly assigned to case group and 50 patients in control group after informed consents of relative obtained. Patients in the case group who being died after got COVID 19 whereas 50 patients in the control group participated who were survive after got infected from COVID 19 patients. Result It has three categories such as a Vaccination status For the vaccination status we have seen 59 patients were not vaccinated and 41 patients was vaccinated out of 100. b Incidence There were 41 patients were vaccinated whereas 59 patients were not vaccinated. c Severity In the case of mortality we selected 50 patients who were died from the Corona and I got to know that out of 50 patients there were 12 24 patients were vaccinated whereas 38 76 patients were non vaccinated. Although for the 50 control survival group total 29 58 patients were vaccinated and 21 42 patients was not vaccinated all graph start. Conclusion we have find out that those people who got vaccinated were less infected and mortality rate very low. Prof. (Dr) Binod Kumar Singh | Dr. Saroj Kumar | Ms. Anuradha Sharma "To Assess the Severity and Mortality among Covid-19 Patients after Having Vaccinated: A Retrospective Study" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-5 , August 2021, URL: https://www.ijtsrd.com/papers/ijtsrd45065.pdf Paper URL: https://www.ijtsrd.com/other-scientific-research-area/other/45065/to-assess-the-severity-and-mortality-among-covid19-patients-after-having-vaccinated-a-retrospective-study/prof-dr-binod-kumar-singh
Fatty liver index correlates with non-alcoholic fatty liver disease, but not ...Enrique Moreno Gonzalez
Fatty liver index (FLI) was recently established to predict non-alcoholic fatty liver disease (NAFLD) in general population, which is known to be associated with coronary artery atherosclerotic disease (CAD).
This study aims to investigate whether FLI correlates with NAFLD and with newly diagnosed CAD in a special Chinese population who underwent coronary angiography.
The cysteinyl leukotriene 2 receptor contributes to all-trans retinoic acid-i...Enrique Moreno Gonzalez
Cysteinyl leukotrienes (CysLTs) are potent pro-inflammatory mediators that are increased in samples from patients with inflammatory bowel diseases (IBDs). Individuals with IBDs have enhanced susceptibility to colon carcinogenesis. In colorectal cancer, the balance between the pro-mitogenic cysteinyl leukotriene 1 receptor (CysLT1R) and the differentiation-promoting cysteinyl leukotriene 2 receptor (CysLT2R) is lost. Further, our previous data indicate that patients with high CysLT1R and low CysLT2R expression have a poor prognosis. In this study, we examined whether the balance between CysLT1R and CysLT2R could be restored by treatment with the cancer chemopreventive agent all-trans retinoic acid (ATRA).
Clinical features and outcome of cryptogenic hepatocellular carcinoma compare...Enrique Moreno Gonzalez
Cryptogenic hepatocellular carcinoma (HCC) is thought to arise due to non-alcoholic fatty liver disease (NAFLD). This study investigated the prevalence, clinical features, and outcomes of cryptogenic HCC and compared them with those of HCC related to hepatitis B virus infection (HBV-HCC), hepatitis C virus infection (HCV-HCC), and alcohol (ALCHCC) in Korea.
Multidrugresistant tuberculosis
Among the most menacing forms of MDR is multidrug
resistant tuberculosis (MDR-TB). WHO estimates that
were about 450,000 new cases and 170,000 deaths from
MDR-TB in 2012. The number of cases reported to
WHO rose by an alarming 35% between 2011 and 2012,
although this probably mostly reflects increased recognition
and reporting. Over half the new cases were in India,
China or the Russian Federation.3
This issue of Homeopathy features a paper by Dr Kusum
Chand and colleagues reporting a randomized, double blind,
placebo-controlled clinical trial of individualized homeopathic
treatment or placebo in addition to standard antituberculous
chemotherapy as specified by the Indian Revised
National Tuberculosis Control Program, for MDR-TB
NON-STEROIDAL ANTI INFLAMMATORY DRUGS AND GASTROINTESTINAL TOXICITYApollo Hospitals
Non-steroidal anti inflammatory drugs (NSAIDs) because of their high efficacy as both anti-inflammatory and analgesic agents, are one of the most commonly prescribed drugs world-wide. They are used in treatment of many commonly occurring disorders such as chronic arthropathies, headache and low back pain. Their widespread and uncontrolled use is promoted by their over the counter availability. This acts as a double edge sword. One of the most common adverse effects that add largely to its morbidity and mortality
is the gastrointestinal tract damage.
Etiologia de la celulitis y Predicción clínica de la enfermedad Estreptocócic...Alex Castañeda-Sabogal
Etiologia de la celulitis. Estudio prospectivo y predicción clínica de la infeccion por Estreptococcus basado en la frecuencia encontrada de las especies de estreptococo
Convalescent Plasma and COVID-19: Ancient Therapy Re-emergedasclepiuspdfs
Convalescent plasma has again re-emerged as a therapy during coronavirus disease (COVID-19) outbreaks currently use as a prophylactic or an interventional treatment in infected patients. Convalescent plasma has been used in the 20th century confronting different infectious diseases where there was no other therapy available. Conceivably, this convalescent plasma therapy tends to be proving a game-changing treatment in some COVID-19 patients and could support treatment, in addition to the current interventions before other developed therapies are available for the population.
Prevalence of Chronic Kidney disease in Patients with Metabolic Syndrome in S...asclepiuspdfs
Background and Objective: Chronic kidney disease (CKD) which is an increasingly important clinical and public health issue is associated with cardiovascular disease. Epidemiologic studies have also linked metabolic syndrome (MetS) with an increased risk of incident CKD. Therefore, the present study was designed retrospectively to find the prevalence and potential risk factors of CKD in patients with MetS in Saudi Arabia.
A Study to Assess the Effectiveness of Planned Teaching Program on the Knowle...ijtsrd
Malnutrition and Tuberculosis chronic infectious disease are both problems of considerable magnitude in the most underdeveloped regions of the world. Malnutrition can leads to secondary immunodeficiency that increase the host susceptibility to infection. The aim of the study was to assess the effectiveness of planned teaching program on the knowledge and practice regarding dietary pattern among mothers of children with tuberculosis admitted in pediatric ward. Quasi experimental with two groups pre test post test design was used for 60 mothers at IPD and OPD of pediatric department and purposive sampling technique was used. Self structured questionnaire was used to assess knowledge and checklist for practice. In post test experimental group mothers have 63.3 average knowledge, 26.6 poor knowledge and 10 good knowledge while in the control group, 53.3 poor knowledge, 46.6 average knowledge and non hove good knowledge. In experimental group mean score was 17.9 1.96 while in control group mean score was 11.8 2.99. At the “p” value 0.05, the calculated t value 3.21 was compared with the tabulated value 2.01 . In post test experimental group, mothers have 53.3 good practice, 46.6 average practice and none have poor practice while in the control group, 63.33 average practice, 23.3 poor practice and 13.3 good practice. In experimental group mean score was 19.13 1.99 while in the control group, mean score was 14.06 2.85.At the “p” value 0.05, the calculated t value 3.28 was compared with the tabulated value 2.01 . These finding reveals that the planned teaching program on dietary pattern was effective. Mrs. Anchal Tiwari | Mrs. Anugrah Charan | Dr. Sarika Gupta "A Study to Assess the Effectiveness of Planned Teaching Program on the Knowledge and Practice Regarding Dietary Pattern among Mothers of Children with Tuberculosis Admitted in Pediatric Ward at KGMU Hospital, Lucknowv" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-2 , February 2021, URL: https://www.ijtsrd.com/papers/ijtsrd38591.pdf Paper Url: https://www.ijtsrd.com/medicine/nursing/38591/a-study-to-assess-the-effectiveness-of-planned-teaching-program-on-the-knowledge-and-practice-regarding-dietary-pattern-among-mothers-of-children-with-tuberculosis-admitted-in-pediatric-ward-at-kgmu-hospital-lucknowv/mrs-anchal-tiwari
Management of Helicobacter pylori infection in Greece: Current guidelines
4th Athens International Symposium on Digestive Diseases, Athens Greece 6-7 July 2018
Chris Zavos, MD, PhD, FEBGH
http://peptiko.gr
To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...YogeshIJTSRD
The severity and mortality of COVID 19 cases has been associated with the Three category such as vaccination status, severity of disease and outcome. Objective presently study was aimed to assess the severity and mortality among covid 19 patients. Methods Using simple lottery random method 100 samples were selected. From these 100 patients, 50 patients were randomly assigned to case group and 50 patients in control group after informed consents of relative obtained. Patients in the case group who being died after got COVID 19 whereas 50 patients in the control group participated who were survive after got infected from COVID 19 patients. Result It has three categories such as a Vaccination status For the vaccination status we have seen 59 patients were not vaccinated and 41 patients was vaccinated out of 100. b Incidence There were 41 patients were vaccinated whereas 59 patients were not vaccinated. c Severity In the case of mortality we selected 50 patients who were died from the Corona and I got to know that out of 50 patients there were 12 24 patients were vaccinated whereas 38 76 patients were non vaccinated. Although for the 50 control survival group total 29 58 patients were vaccinated and 21 42 patients was not vaccinated all graph start. Conclusion we have find out that those people who got vaccinated were less infected and mortality rate very low. Prof. (Dr) Binod Kumar Singh | Dr. Saroj Kumar | Ms. Anuradha Sharma "To Assess the Severity and Mortality among Covid-19 Patients after Having Vaccinated: A Retrospective Study" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-5 , August 2021, URL: https://www.ijtsrd.com/papers/ijtsrd45065.pdf Paper URL: https://www.ijtsrd.com/other-scientific-research-area/other/45065/to-assess-the-severity-and-mortality-among-covid19-patients-after-having-vaccinated-a-retrospective-study/prof-dr-binod-kumar-singh
Fatty liver index correlates with non-alcoholic fatty liver disease, but not ...Enrique Moreno Gonzalez
Fatty liver index (FLI) was recently established to predict non-alcoholic fatty liver disease (NAFLD) in general population, which is known to be associated with coronary artery atherosclerotic disease (CAD).
This study aims to investigate whether FLI correlates with NAFLD and with newly diagnosed CAD in a special Chinese population who underwent coronary angiography.
The cysteinyl leukotriene 2 receptor contributes to all-trans retinoic acid-i...Enrique Moreno Gonzalez
Cysteinyl leukotrienes (CysLTs) are potent pro-inflammatory mediators that are increased in samples from patients with inflammatory bowel diseases (IBDs). Individuals with IBDs have enhanced susceptibility to colon carcinogenesis. In colorectal cancer, the balance between the pro-mitogenic cysteinyl leukotriene 1 receptor (CysLT1R) and the differentiation-promoting cysteinyl leukotriene 2 receptor (CysLT2R) is lost. Further, our previous data indicate that patients with high CysLT1R and low CysLT2R expression have a poor prognosis. In this study, we examined whether the balance between CysLT1R and CysLT2R could be restored by treatment with the cancer chemopreventive agent all-trans retinoic acid (ATRA).
Clinical features and outcome of cryptogenic hepatocellular carcinoma compare...Enrique Moreno Gonzalez
Cryptogenic hepatocellular carcinoma (HCC) is thought to arise due to non-alcoholic fatty liver disease (NAFLD). This study investigated the prevalence, clinical features, and outcomes of cryptogenic HCC and compared them with those of HCC related to hepatitis B virus infection (HBV-HCC), hepatitis C virus infection (HCV-HCC), and alcohol (ALCHCC) in Korea.
Implication from thyroid function decreasing during chemotherapy in breast ca...Enrique Moreno Gonzalez
Thyroid hormones have been shown to regulate breast cancer cells growth, the absence or reduction of thyroid hormones in cells could provoke a proliferation arrest in G0-G1 or weak mitochondrial activity, which makes cells insensitive to therapies for cancers through transforming into low metabolism status. This biological phenomenon may help explain why treatment efficacy and prognosis vary among breast cancer patients having hypothyroid, hyperthyroid and normal function. Nevertheless, the abnormal thyroid function in breast cancer patients has been considered being mainly caused by thyroid diseases, few studied influence of chemotherapy on thyroid function and whether its alteration during chemotherapy can influence the respose to chemotherapy is still unclear. So, we aimed to find the alterations of thyroid function and non-thyroidal illness syndrome (NTIS) prevalence druing chemotherapy in breast cancer patients, and investigate the influence of thyroid hormones on chemotherapeutic efficacy.
Association between variations in the fat mass and obesity-associated gene an...Enrique Moreno Gonzalez
It is clear that genetic variations in the fat mass and obesity-associated (FTO) gene affect body mass index and the risk of obesity. Given the mounting evidence showing a positive association between obesity and pancreatic cancer, this study aimed to investigate the relation between variants in the FTO gene, obesity and pancreatic cancer risk.
Sticky siRNAs targeting survivin and cyclin B1 exert an antitumoral effect on...Enrique Moreno Gonzalez
Melanoma represents one of the most aggressive and therapeutically challenging malignancies as it often gives rise to metastases and develops resistance to classical chemotherapeutic agents. Although diverse therapies have been generated, no major improvement of the patient prognosis has been noticed. One promising alternative to the conventional therapeutic approaches currently available is the inactivation of proteins essential for survival and/or progression of melanomas by means of RNA interference. Survivin and cyclin B1, both involved in cell survival and proliferation and frequently deregulated in human cancers, are good candidate target genes for siRNA mediated therapeutics.
Intraepithelial lymphocyte distribution differs between the bulb and the seco...Enrique Moreno Gonzalez
Evaluation of intraepithelial duodenal lymphocytosis (IDL) is important in celiac disease (CD). There is no established cut-off value for increased number of IELs in the bulb. We therefore investigated the relation between IEL counts in the bulb and duodenal specimens in non-celiac subjects.
Optimal schedule of Bacillus Calmette-Guerin for non-muscle-invasive bladder ...Enrique Moreno Gonzalez
To explore the necessity of maintenance, efficacy of low-dose and superiority of various combination therapies of Bacillus Calmette-Guérin (BCG) in treatment of superficial bladder cancer (BCa).
Periodontal Disease Indices and Colorectal Cancer Risk in Greek Adults: A Cas...asclepiuspdfs
Introduction: The previous researches have recorded positive associations between periodontal disease (PD) and risk of cancer at various locations. The aim of the present case–control study was to investigate the possible associations between PD indices and the risk of colorectal cancer (CRC) development in a sample of Greek outpatients referred to a medical and dental private practice. Materials and Methods: A total of 342 individuals were interviewed and underwent an oral clinical examination, and 85 of them were suffered from CRC at various anatomic locations. The evaluation of the possible associations between CRC and PD indices was performed using a regression analysis model. Results: Clinical attachment loss (CAL) (P = 0.042, odds ratio [OR] = 1.78, 95% confidence interval [CI] = 1.02–3.11) was significantly associated with the risk of developing CRC. CRC family history (P = 0.002, OR = 2.33, 95% CI = 1.35–4.03) and smoking (P = 0.019, OR = 1.96, 95% CI = 1.12–3.45) were also significantly associated with the mentioned risk, whereas smoking was found to be nota confounder regarding the estimated association between moderate/severe CAL with the risk of developing CRC. Conclusion: CAL as an index for PD severity was statistically significantly associated with the risk of developing CRC.
Epidemiological studies are applicable to communicable and non-com.docxSALU18
Epidemiological studies are applicable to communicable and non-communicable diseases. Childhood obesity is an area that is receiving more attention in public health due to the multiple morbidities that emerge as a result of this condition. Below are links to a cross-sectional study and a case-control study. Imagine that you are interested in conducting a case-control or cross-sectional study proposal of childhood obesity vs. birth weight (prenatal and early life influences). Both articles below address prenatal influences on childhood obesity and birth weight using different approaches.
Article 1 -attached
Article 2-attached
Using the information in the articles, answer the following questions using AMA format.
1. How would you select cases and controls for this study and how would you define exposure and outcome variables for a case-control study design? What other factors would you control for?
2. How would you design a proposal measuring the effect of birthweight on childhood obesity for a cross-sectional study design? What other factors would you control for?
BioMed CentralBMC Public Health
ss
Open AcceStudy protocol
Cross sectional study of childhood obesity and prevalence of risk
factors for cardiovascular disease and diabetes in children aged 11–
13
Anwen Rees*1, Non Thomas1, Sinead Brophy2, Gareth Knox1 and
Rhys Williams2
Address: 1Cardiff School of Sport, University of Wales Institute Cardiff, Wales, UK and 2School of Medicine, Swansea University, Wales, UK
Email: Anwen Rees* - [email protected]; Non Thomas - [email protected]; Sinead Brophy - [email protected];
Gareth Knox - [email protected]; Rhys Williams - [email protected]
* Corresponding author
Abstract
Background: Childhood obesity levels are rising with estimates suggesting that around one in
three children in Western countries are overweight. People from lower socioeconomic status and
ethnic minority backgrounds are at higher risk of obesity and subsequent CVD and diabetes.
Within this study we examine the prevalence of risk factors for CVD and diabetes (obesity,
hypercholesterolemia, hypertension) and examine factors associated with the presence of these
risk factors in school children aged 11–13.
Methods and design: Participants will be recruited from schools across South Wales. Schools
will be selected based on catchment area, recruiting those with high ethnic minority or deprived
catchment areas. Data collection will take place during the PE lessons and on school premises. Data
will include: anthropometrical variables (height, weight, waist, hip and neck circumferences, skinfold
thickness at 4 sites), physiological variables (blood pressure and aerobic fitness (20 metre multi
stage fitness test (20 MSFT)), diet (self-reported seven-day food diary), physical activity (Physical
Activity Questionnire for Adolescents (PAQ-A), accelerometery) and blood tests (fasting glucose,
insulin, lipids, fibrinogen (Fg), adiponectin (high molecular weight), C-react ...
Role of life events in the presence of colon polyps among African AmericansEnrique Moreno Gonzalez
African Americans have disproportionately higher incidence and death rates of colorectal cancer among all ethnic groups in the United States. Several lifestyle factors (e.g. diet, physical activity and alcohol intake) have been suggested as risk factors for colorectal cancer. Stressful life events have also been identified as risk factors for colorectal cancer. The association between stressful life events and colon polyps, which are precursors of colorectal
cancer, has yet to be determined.
Low prevalence of ‘classical’ microscopic colitis but evidence of microscopic...Enrique Moreno Gonzalez
There is increasing evidence for the role of microscopic inflammation in patients with IBS.
We aimed to examine the prevalence of microscopic colitis and inflammation in Malaysian
IBS patients with diarrhoea (IBS-D).
A Mathematical Model of the Dynamics of Hepatitis B Virus (HBV) Infection wit...ijtsrd
In this model we study the dynamics and control of hepatitis B virus (HBV) infection which is a major health problem worldwide by considering condom, vaccination and treatment as control measures. Initially we determined the basic reproduction number R_0 for the model and observe that once R_0 http://www.ijtsrd.com/mathemetics/other/18164/a-mathematical-model-of-the-dynamics-of-hepatitis-b-virus-hbv-infection-with-controls/titus-ifeanyi-chinebu
Similar to Antibiotic exposure and the development of coeliac disease: a nationwide case--control study (20)
Incidence of pneumonia and risk factors among patients with head and neck can...Enrique Moreno Gonzalez
This study investigated the incidence and patient- and treatment-related risk factors related to pneumonia acquired during radiotherapy (PNRT) in head and neck cancer (HNC) patients.
Gene expression analysis of a Helicobacter pyloriinfected and high-salt diet-...Enrique Moreno Gonzalez
Helicobacter pylori (H. pylori) infection and excessive salt intake are known as important risk factors for stomach cancer in humans. However, interactions of these two factors with gene expression profiles during gastric carcinogenesis remain unclear. In the present study, we investigated the global gene expression associated with stomach carcinogenesis and prognosis of human gastric cancer using a mouse model.
Acute myeloid leukemia (AML) is a hematopoietic malignancy with a dismal outcome in the majority of cases. A detailed understanding of the genetic alterations and gene expression changes that contribute to its pathogenesis is important to improve prognostication, disease monitoring, and therapy. In this context, leukemia-associated misexpression of microRNAs (miRNAs) has been studied, but no coherent picture has emerged yet, thus warranting further investigations.
Recently, a phase II clinical trial in hepatocellular carcinoma (HCC) has suggested that the combination of sorafenib and 5-fluorouracil (5-FU) is feasible and side effects are manageable. However, preclinical experimental data explaining the interaction mechanism(s) are lacking. Our objective is to investigate the anticancer efficacy and mechanism of combined sorafenib and 5-FU therapy in vitro in HCC cell lines MHCC97H and SMMC-7721.
Differences in microRNA expression during tumor development in the transition...Enrique Moreno Gonzalez
The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ), and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation for the difference in propensity of tumors in the zones of the prostate.
Multicentric and multifocal versus unifocal breast cancer: differences in the...Enrique Moreno Gonzalez
The aim of this study was to evaluate the expression of the cell adhesion-related glycoproteins MUC-1, β-catenin and E-cadherin in multicentric/multifocal breast cancer in comparison to unifocal disease in order to identify potential differences in the biology of these tumor types.
The life in sight application study (LISA): design of a randomized controlled...Enrique Moreno Gonzalez
It is widely recognized that spiritual care plays an important role in physical and psychosocial well-being of cancer patients, but there is little evidence based research on the effects of spiritual care. We will conduct a randomized controlled trial on spiritual care using a brief structured interview scheme supported by an e-application. The aim is to examine whether an assisted reflection on life events and ultimate life goals can improve quality of life of cancer patients.
Clinical and experimental studies regarding the expression and diagnostic val...Enrique Moreno Gonzalez
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a multifunctional Ig-like cell adhesion molecule that has a wide range of biological functions. According to previous reports, serum CEACAM1 is dysregulated in different malignant tumours and associated with tumour progression. However, the serum CEACAM1 expression in nonsmall-cell lung carcinomas (NSCLC) is unclear. The different expression ratio of CEACAM1-S and CEACAM1-L isoform has seldom been investigated in NSCLC. This research is intended to study the serum CEACAM1 and the ratio of CEACAM1-S/L isoforms in NSCLC.
Assessment of preoperative exercise capacity in hepatocellular carcinoma pati...Enrique Moreno Gonzalez
Cardiopulmonary exercise testing measures oxygen uptake at increasing levels of work and predicts cardiopulmonary performance under conditions of stress, such as after abdominal surgery. Dynamic assessment of preoperative exercise capacity may be a useful predictor of postoperative prognosis. This study examined the relationship between preoperative exercise capacity and event-free survival in hepatocellular carcinoma (HCC) patients with chronic liver injury who underwent hepatectomy.
Overexpression of YAP 1 contributes to progressive features and poor prognosi...Enrique Moreno Gonzalez
Yes-associated protein 1 (YAP 1), the nuclear effector of the Hippo pathway, is a key regulator of organ size and a candidate human oncogene in multiple tumors. However, the expression dynamics of YAP 1 in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance are unclear.
CXCR7 is induced by hypoxia and mediates glioma cell migration towards SDF-1a...Enrique Moreno Gonzalez
Glioblastomas, the most common and malignant brain tumors of the central nervous system, exhibit high invasive capacity, which hinders effective therapy. Therefore, intense efforts aimed at improved therapeutics are ongoing to delineate the molecular mechanisms governing glioma cell migration and invasion.
Abnormal expression of Pygopus 2 correlates with a malignant phenotype in hum...Enrique Moreno Gonzalez
Pygopus 2 (Pygo2) is a Pygo family member and an important component of the Wnt signaling transcriptional complex. Despite this data, no clinical studies investigating Pygo2 expression in lung cancer have yet been reported.
Differentiation of irradiation and cetuximab induced skin reactions in patien...Enrique Moreno Gonzalez
In order to improve the clinical outcome of patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN) not being capable to receive platinum-based chemoradiation, radiotherapy can be intensified by addition of cetuximab, a monoclonal antibody that blocks the epidermal growth factor receptor (EGFR). The radioimmunotherapy with cetuximab is a feasible treatment option showing a favourable toxicity profile. The most frequent side effect of radiotherapy is radiation dermatitis, the most common side effect of treatment with cetuximab is acneiform rash. Incidence and severity of these frequent, often overlapping and sometimes limiting skin reactions, however, are not well explored. A clinical and molecular differentiation between radiogenic skin reactions and skin reactions caused by cetuximab which may correlate with outcome, have never been described before.
Cholestasis induces reversible accumulation of periplakin in mouse liverEnrique Moreno Gonzalez
Periplakin (PPL) is a rod-shaped cytolinker protein thought to connect cellular adhesion junctional complexes to cytoskeletal filaments. PPL serves as a structural component of the cornified envelope in the skin and interacts with various types of proteins in cultured cells; its level decreases dramatically during tumorigenic progression in human epithelial tissues. Despite these intriguing observations, the physiological roles of PPL, especially in noncutaneous tissues, are still largely unknown. Because we observed a marked fluctuation of PPL expression in mouse liver in association with the bile acid receptor farnesoid X receptor (FXR) and cholestasis, we sought to characterize the role of PPL in the liver and determine its contributions to the etiology and pathogenesis of cholestasis.
Functional p53 is required for rapid restoration of daunorubicin-induced lesi...Enrique Moreno Gonzalez
The tumour suppressor and transcription factor p53 is a major determinant of the therapeutic response to anthracyclines. In healthy tissue, p53 is also considered pivotal for side effects of anthracycline treatment such as lesions in haematopoietic tissues like the spleen. We used a Trp53null mouse to explore the significance of p53 in anthracycline (daunorubicin) induced lesions in the spleen.
Post-diagnosis hemoglobin change associates with overall survival of multiple...Enrique Moreno Gonzalez
Anemia refers to low hemoglobin (Hb) level and is a risk factor of cancer patient survival. The National Comprehensive Cancer Network recently suggested that post-diagnosis Hb change, regardless of baseline Hb level, indicates the potential presence of anemia. However, there is no epidemiological study evaluating whether Hb change has direct prognostic values for cancer patients at the population level.
Cost-effectiveness of MRI for breast cancer screening in BRCA1/2 mutation car...Enrique Moreno Gonzalez
Women with mutations in BRCA1 or BRCA2 are at high risk of developing breast cancer and, in British Columbia, Canada, are offered screening with both magnetic resonance imaging (MRI) and mammography to facilitate early detection. MRI is more sensitive than mammography but is more costly and produces more false positive results. The purpose of this study was to calculate the cost-effectiveness of MRI screening for breast cancer in BRCA1/2 mutation carriers in a Canadian setting.
Impaired mitochondrial beta-oxidation in patients with chronic hepatitis C: r...Enrique Moreno Gonzalez
Hepatic steatosis is often seen in patients with chronic hepatitis C (CH-C). It is still unclear whether these patients have an impaired mitochondrial β-oxidation. In this study we assessed mitochondrial β-oxidation in CH-C patients by investigating ketogenesis during fasting.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
2. Antibiotic exposure and the development of coeliac
disease: a nationwide case–control study
Karl Mårild1,2,*
Email: karlmarild@gmail.com
Weimin Ye3
Email: Weimin.Ye@ki.se
Benjamin Lebwohl4
Email: bl114@mail.cumc.columbia.edu
Peter HR Green4
Email: pg11@columbia.edu
Martin J Blaser5
Email: Martin.Blaser@nyumc.org
Tim Card6
Email: Tim.Card@nottingham.ac.uk
Jonas F Ludvigsson1,7
Email: jonasludvigsson@yahoo.com
1
Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden
2
Astrid Lindgren Children’s Hospital, Solna, Sweden
3
Department of Medical Epidemiology & Biostatistics, Karolinska Institutet,
Stockholm, Sweden
4
Celiac Disease Center, Department of Medicine, Columbia University Medical
Center, Columbia University, New York, USA
5
Department of Medicine, New York University Langone Medical Center, New
York, USA
6
Division of Epidemiology and Public Health, University of Nottingham,
Nottingham City Hospital, Nottingham, UK
7
Department of Paediatrics, Örebro University Hospital, Örebro, Sweden
*
Corresponding author. Astrid Lindgren Children’s Hospital, Solna, Sweden
3. Abstract
Background
The intestinal microbiota has been proposed to play a pathogenic role in coeliac disease
(CD). Although antibiotics are common environmental factors with a profound impact on
intestinal microbiota, data on antibiotic use as a risk factor for subsequent CD development
are scarce.
Methods
In this population-based case–control study we linked nationwide histopathology data on
2,933 individuals with CD (Marsh stage 3; villous atrophy) to the Swedish Prescribed Drug
Register to examine the association between use of systemic antibiotics and subsequent CD.
We also examined the association between antibiotic use in 2,118 individuals with
inflammation (Marsh 1–2) and in 620 individuals with normal mucosa (Marsh 0) but positive
CD serology. All individuals undergoing biopsy were matched for age and sex with 28,262
controls from the population.
Results
Antibiotic use was associated with CD (Odds ratio [OR] = 1.40; 95% confidence interval [CI]
= 1.27-1.53), inflammation (OR = 1.90; 95% CI = 1.72–2.10) and normal mucosa with
positive CD serology (OR = 1.58; 95% CI = 1.30–1.92). ORs for prior antibiotic use in CD
were similar when we excluded antibiotic use in the last year (OR = 1.30; 95% CI = 1.08-
1.56) or restricted to individuals without comorbidity (OR = 1.30; 95% CI = 1.16 – 1.46).
Conclusions
The positive association between antibiotic use and subsequent CD but also with lesions that
may represent early CD suggests that intestinal dysbiosis may play a role in the pathogenesis
of CD. However, non-causal explanations for this positive association cannot be excluded.
Keywords
Celiac, Inflammation, Microbiota, Population-based case–control study
Background
Coeliac disease (CD) is a life-long autoimmune disease prevalent in 1 to 2% of the western
population [1]. CD is a multifactorial disease where genetically predisposed individuals
develop small-intestinal villous atrophy and inflammation in response to dietary gluten intake
[2]. In recent decades, the prevalence of CD has more than doubled, [3] strongly indicating
that environmental factors other than gluten-exposure may have a significant influence on CD
development [4]. Further, data from the “Swedish celiac epidemic”, where childhood CD
incidence displayed an epidemic pattern with a rapid four-fold increase in incidence in 1984
4. and a later abrupt decline in 1996, coinciding with changed infant feeding recommendations,
have suggested that environmental factors influence CD development [5].
Today, half of all children in many Western countries receive antibiotics at least once a year
[6]. Antibiotics can have both short- and long-term effects on the ecological balance between
the host and the normal microbiota [7,8]. The intestinal microbiota influences the
development of the intestinal immune system, the establishment of oral tolerance and the
mucosal barrier function [9]. Previous research has found a difference in the gut microbiota
between individuals with CD and healthy controls, suggesting that a dysbiotic microbiota
may play a pathogenic role in CD [10]. Despite the profound impact of antibiotics on the gut
microbiome, there are few data on antibiotic exposure and risk of CD.
The main objective of this case–control study was to examine the association between
antibiotic use and subsequent CD by comparing individuals with CD with matched controls
from the general population. We also examined antibiotic use in individuals who may have
early CD without villous atrophy [11] (I) small-intestinal inflammation without villous
atrophy, or (II) normal small-intestinal mucosa but positive CD serology. Studying these
early CD manifestations may be important because risk factors may not only influence the
fully developed disease, but sometimes have an even stronger association with disease
precursors. For example, cigarette smoking has been more strongly associated with colorectal
adenomas compared with colorectal cancer [12,13].
Methods
In this case–control study we linked nationwide histopathology data on individuals
undergoing small intestinal biopsy to the Swedish Prescribed Drug Register in order to
examine the association between use of antibiotics and CD. We hypothesized a positive
association between antibiotic use and CD.
Literature search
A literature search at PubMed (http://pubmed.gov/) was performed using the following
combinations of words as our major search terms: “celiac”, “coeliac”, “antibiotic” and
“antimicrobial”.
Study population
Between 2006 and 2008, we searched the computerized register of Sweden’s 28 pathology
departments to identify individuals with CD [14]. In this study CD was defined as small-
intestinal villous atrophy (Marsh grade 3) [15]. An earlier evaluation has shown that 95% of
Swedish individuals with villous atrophy have CD [14]. To examine the context of the
association between antibiotic use and subsequent CD we also identified individuals with
small-intestinal inflammation (Marsh grade 1–2) but without villous atrophy and individuals
with normal small-intestinal mucosa (Marsh grade 0) but with positive CD serology [16]. The
biopsies were performed between July 1969 and January 2008 [17]. A detailed account of the
data collection process has been described elsewhere [14,16].
In the current study we used the same dataset described in our previous study of mortality
(29,096 individuals with CD, 13,306 individuals with inflammation, 3,719 individuals with
5. normal mucosa but positive CD serology) [18]. Data on individuals with normal mucosa and
positive CD serology were regional and obtained from the ascertainment areas of eight
Swedish university hospitals covering approximately half of the Swedish population [16].
Positive CD serology was defined as a positive IgA or IgG AGA (antigliadin), EMA
(endomysial), or TTG (tissue transglutaminase) test less than 180 days before or no later than
30 days after a normal biopsy (and with no prior or subsequent biopsy showing villous
atrophy or inflammation) [16]. In a recent consensus paper individuals with normal mucosa
and positive CD serology were identified as having potential CD [11].
For each individual undergoing biopsy, the government agency Statistics Sweden identified
up to five controls from the population matched for age, sex, calendar period of birth and
county of residence. For example, a girl living in the county of Blekinge, diagnosed with CD
in 2006 at the age of 13 years; was matched with five 13-year-old girls who were living in
Blekinge in 2006. After exclusion of individuals with data irregularities, [18] we identified
228,632 controls (Figure 1).
Figure 1 Flow chart of exclusion criteria. CD, Coeliac disease.
Individuals undergoing biopsy and their matched controls were then linked to the Swedish
Prescribed Drug Register (established on July 1st 2005) [19]. Through this linkage, we
identified individuals biopsied between July 1st 2005 and January 29th 2008 (end of the
study period). Thus, the final analyses included 2,933 individuals with CD, 2,118 individuals
with inflammation, 620 individuals with normal mucosa but positive CD serology and 28,262
controls (Figure 1).
Antibiotic use
The Swedish Prescribed Drug Register contains prospectively recorded individual data (on
e.g. date of dispensing) on more than 99% of all dispensed prescribed drugs in Sweden [19].
Antibiotics in Sweden are not sold over the counter.
We collected data on use of all systemic antibiotics (anatomical therapeutic chemical, ATC
code: J01) from July 1st 2005 (launch of the Prescribed Drug Register) through January 29th
2008 (end of the study period), and up to the date of the biopsy (and the corresponding date
in matched controls). Antibiotics were grouped into penicillin V, extended-spectrum
penicillins, quinolones, macrolides and other systemic antibiotics (Additional file 1).
Statistical analyses
We used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence
intervals (CIs). Each stratum (one individual undergoing biopsy and up to five matched
controls) was analyzed separately before a summary OR was calculated.
In our main analysis we examined the association between use of any systemic antibiotics
and subsequent CD. Early-onset CD (i.e. before the age of 2 years) may have different risk
factors compared with late-onset CD [5]. Additionally, antibiotic exposure early in life may
have a more profound impact on the composition of the microbiota [20]. Accordingly, we
performed stratified analyses by age at CD diagnosis (<2 years, 2–19 years, 20–39 years, 40–
59 years and ≥60 years). We also stratified our analyses for sex. Similar sub-analyses were
performed for individuals with small-intestinal inflammation and individuals with normal
6. small-intestinal mucosa but positive CD serology. For each of these stratifications we
examined for interaction via the inclusion in our models of multiplicative interaction terms,
and the use of likelihood ratio tests between models with and without them.
Antibiotics differ in their influence on the intestinal microbiota. In pre-planned sub-analyses
we estimated the association between CD and type of antibiotic exposure: penicillin V,
extended-spectrum penicillins, quinolones, macrolides and other systemic antibiotics. This
grouping of antibiotics has previously been used [21,22] and is largely based on the ATC
classification system where the subgroups indicate the different therapeutic indications of
antibacterial agents. To evaluate potential causality we estimated the dose- and time-
dependent association between antibiotic use and CD in two separate analyses: (1) when
individuals had received 1–2 courses and at least 3 courses of antibiotics and (2) when
antibiotics had been prescribed in the year (≤365 days) before biopsy.
Education level has been associated with antibiotic use [23] and may influence the risk of CD
diagnosis [24]. In a sub-analysis we therefore adjusted for education using seven predefined
education categories determined by Statistics Sweden.
Post-hoc analyses
Certain antiparasitic medications have similar pharmacokinetic and pharmacodynamic
properties as systemic antibiotics with a strong impact on the gut microbiota. In a post-hoc
analysis we therefore examined the relationship between use of any antiparasitic medications
(ATC codes P01-P03, e.g. oral tinidazole) and CD, as well as specifically the use of
metronidazole and CD.
Individuals with undiagnosed CD have an increased risk of comorbidity, [25] and with that,
potentially increased surveillance and probability to receive antibiotic treatment. In a post-
hoc analysis we therefore restricted our data to individuals who had not been admitted to a
hospital during the study period. Hospital admission data were collected from the national
Inpatient Register [26].
To further reduce the risk of surveillance bias we constructed a variable representing
outpatient health care consumption. Hospital-based outpatient care has been recorded
nationally in Sweden since January 1st 2001. We calculated the number of hospital-based
outpatient visits from birth or start of the registry (whichever occurred latest) until the day
before small-intestinal biopsy (or corresponding date in matched controls). We excluded
visits in which CD was coded as the main reason for the visit. Individuals then were divided
into four groups according to number of visits per year (those with no record of prior
hospital-based outpatient care (0); >0 but <1 visit/year; 1- < 2 visits/year; and ≥2 visits/year).
Those individuals with no record of hospital-based outpatient care may have undergone
initial CD investigation in primary care before undergoing biopsy. For example: A patient A,
undergoing biopsy in December 2006, with eight hospital-based outpatient visits in the six
years between 2001 (start of registration of outpatient data) and December 2006 (time of
biopsy) has an average of 1.3 visits per year (= 8 visits/6 years). In a post-hoc analysis, we
added this variable to our statistical model to evaluate whether the association between
antibiotic exposure and CD remained.
CD is elicited by dietary gluten and thus virtually nonexistent before the age of six months.
To establish whether antibiotic use truly preceded CD, i.e. to evaluate the risk of reverse
7. causation, we performed a sub-analysis of individuals who were exposed to antibiotics before
the age of six months. In an additional post-hoc analysis we limited our exposure to antibiotic
more than one year (>365 days) before CD diagnosis.
SPSS version 20.0 was used for all statistical analyses.
Ethics
This study was conducted in accordance with the national and institutional standards and was
approved by the Regional Ethical Vetting Board in Stockholm.
Results
The median age at CD diagnosis in this study was 28 years. About 40% of those with CD
were diagnosed in childhood and the majority of study participants were female (Table 1).
Table 1 Descriptive characteristics of individuals with coeliac disease, small-intestinal
inflammation, and normal small-intestinal mucosaa
Coeliac disease Inflammation Normal mucosaa
Total 2933 2118 620
Females (%) 1796 (61.2) 1336 (63.1) 396 (63.9)
Males (%) 1137 (38.8) 782 (36.9) 224 (36.1)
Age at study entry years (median; range) 28; 0-94 43; 0-98 36; 0-84
Age 0–19 (%) 1218 (41.5) 225 (10.6) 150 (24.2)
Age 20–39 (%) 566 (19.3) 684 (32.3) 202 (32.6)
Age 40–59 (%) 583 (19.9) 661 (31.2) 164 (26.5)
Age 60+ (%) 566 (19.3) 548 (25.9) 104 (16.8)
2005b
(%) 819 (27.9) 419 (19.8) 149 (24.0)
2006 (%) 1828 (62.3) 1074 (50.7) 304 (49.0)
2007 C
(%) 274 (9.3) 582 (27.5) 167 (26.9)
2008 D
(%) 12 (0.4) 43 (2.0) -
a
Positive coeliac disease serology (IgA/IgG endomysial, tissue transglutaminase and antigliadin antibodies) 180
days before biopsy and until 30 days after biopsy in individuals with normal mucosa. Endomysial and tissue
transglutaminase antibodies [IgA]: n = 139; Antigliadin antibodies [IgA/IgG] and endomysial and tissue
transglutaminase antibodies [IgG]: n = 481.
b
Beginning of study period: July 1st 2005.
c
The majority of the pathology departments delivered data on individuals with small-intestinal pathology
undergoing biopsy up to the beginning of year 2007. The remaining pathology departments reported
histopathology data to the end of 2007 or very early 2008. For this reason, our data included fewer individuals
with CD diagnosed in 2007 compared with 2006.
D
End of study period: January 29th 2008.
Reference individuals have not been included in the table because their age, sex and entry year distributions
were identical to those of the individuals undergoing biopsy (due to matching).
Of the 2,933 individuals with CD, 27.0% had received at least one course of antibiotics
during the study period before biopsy as compared with 21.1% in the controls, corresponding
to an odds ratio for subsequent CD of 1.40 (95% CI = 1.27-1.53) (Table 2). In the individuals
with inflammation but no villous atrophy 39.5% had used antibiotics as compared with
25.7% in the controls (OR = 1.90; 95% CI = 1.72–2.10). Antibiotic use also was associated
with having a normal small-intestinal mucosa but positive CD serology (Table 2). Restricting
our analysis to individuals with normal mucosa and positive IgA EMA or TTG did not
8. influence the OR (Additional file 2). Adjustment for education level revealed unchanged ORs
in all three groups (Additional file 2).
9. Table 2 Odds ratios for prior antibiotic use in individuals with coeliac disease, small-intestinal inflammation and normal mucosaa
Coeliac disease Inflammation Normal mucosa a
Cases Controls
Odds ratio 95% CI
Cases Controls
Odds ratio 95% CI
Cases Controls
Odds ratio 95% CI
(%) (%) (%) (%) (%) (%)
Any antibioticsb
793/2933 (27.0) 3081/14571 (21.1) 1.40 1.27-1.53 836/2118 (39.5) 2687/10442 (25.7) 1.90 1.72–2.10 205/620 (33.1) 757/3069 (24.7) 1.58 1.30–1.92
Courses of antibiotics
1-2 courses 639/2779 (23.0) 2573/14063 (18.3) 1.36 1.23-1.50 619/1901 (32.6) 2146/9901 (21.7) 1.75 1.57-1.95 153/568 (26.9) 621/2933 (21.2) 1.45 1.17-1.80
≥3 courses 154/2294 (6.7) 508/11998 (4.2) 1.58 1.31-1.92 217/1499 (14.5) 541/8296 (6.5) 2.50 2.10-2.97 52/467 (11.1) 136/2448 (5.6) 2.28 1.56-3.33
Sex
Males 278/1137 (24.5) 1026/5645 (18.2) 1.48 1.27-1.72 282/782 (36.1) 824/3848 (21.4) 2.10 1.78-2.48 69/224 (30.8) 217/1099 (19.7) 1.93 1.38–2.69
Females 515/1796 (28.7) 2055/8926 (23.0) 1.36 1.21-1.52 554/1336 (41.5) 1863/6594 (28.3) 1.81 1.60-2.04 136/396 (34.3) 540/1970 (27.4) 1.43 1.12–1.82
Odds ratios estimated through conditional logistic regression modelling.
a
Positive coeliac disease serology 180 days before biopsy and until 30 days after biopsy in individuals with normal mucosa.
b
Antibiotics used between July 1st 2005 and January 29th 2008.
10. We found increasing ORs for repeated use of antibiotics and subsequent CD diagnosis (1–2
courses of antibiotics: OR = 1.36, 95% CI = 1.23-1.50; ≥3 courses of antibiotics: OR = 1.58,
95% CI = 1.31 - 1.92). Also in individuals with a biopsy showing inflammation or normal
mucosa, but with positive CD serology, we found increasing ORs for repeated use of
antibiotics, indicating a dose–response effect (Table 2).
The association between antibiotic treatment and subsequent CD was similar in males and
females (Males: OR = 1.48, 95% CI = 1.27-1.72; Females: OR = 1.36; 95% CI = 1.21-1.52;
p-value for interaction: 0.38). The stratified analyses by sex for individuals with small-
intestinal inflammation and individuals with normal mucosa but positive CD serology are
also presented in Table 2 (p-value for interaction, inflammation: 0.16; normal mucosa: 0.15).
The stratified analyses by age at biopsy revealed only small differences between age groups
and ORs for antibiotic treatment and development of CD, small-intestinal inflammation or
normal mucosa but positive CD serology (Additional file 3). ORs for previous antibiotic
treatment did not differ appreciably according to year of CD diagnosis (Additional file 3).
Overall, penicillin V was the most frequently prescribed antimicrobials, being used by 9.0%
of the controls and nearly 10% of those with CD. Use of penicillin V was not associated with
CD (OR = 1.12; 95% = 0.98 – 1.27). However, we found an association between use of each
of the remaining types of antibiotic and subsequent CD, with essentially similar ORs,
irrespective of antibiotic type (Table 3).
Table 3 Odds ratios for prior antibiotic a
use in individuals with coeliac disease
Coeliac disease
Cases Controls Odds ratio 95% CI
n = 2,933 (%) n = 14,571 (%)
Type of antibiotics used b
Penicillin V 291 (9.9) 1308 (9.0) 1.12 0.98 – 1.27
Extended spectrum penicillins 183 (6.2) 657 (4.5) 1.38 1.18 – 1.63
Quinolones 51 (1.7) 170 (1.2) 1.46 1.08 – 1.97
Macrolides 53 (1.8) 180 (1.2) 1.44 1.07 – 1.93
Other systemic antibiotics 291 (9.9) 1041 (7.1) 1.42 1.24 – 1.62
Antibiotic use in the last year preceding
diagnosis/study entry
Any antibiotic 722 (24.6) 2730 (18.7) 1.42 1.29 - 1.56
Penicillin V 259 (8.8) 1162 (8.0) 1.12 0.97 - 1.28
Extended spectrum penicillins 166 (5.7) 559 (3.8) 1.46 1.23 - 1.74
Quinolones 45 (1.5) 153 (1.1) 1.43 1.04 - 1.98
Macrolides 48 (1.6) 150 (1.0) 1.55 1.13 - 2.11
Other systemic antibiotics 206 (8.9) 905 (6.2) 1.47 1.26 - 1.66
Odds ratios estimated through conditional logistic regression modelling.
a
See Additional file 4 for anatomical therapeutic chemical codes used to classify systemic antibiotics (J01).
b
Antibiotics used between July 1st 2005 and January 29th 2008.
Twenty-five percent of the individuals with CD had received at least one course of antibiotics
in the year before CD diagnosis compared with 18.7% of the matched controls (OR = 1.42;
95% CI = 1.29 - 1.56). ORs for type of antibiotic, according to ATC code, used in the year
(≤365 days) before CD diagnosis are presented in Table 3.
11. Post-hoc analyses
In a post-hoc analysis 115 individuals with CD (3.9%) and 259 controls (1.8%) had an earlier
record of antiparasitic medication, equivalent to an OR of 2.12 for subsequent CD (95% CI =
1.72 - 2.62). Looking specifically at the earlier use of metronidazole revealed a slightly
stronger association with CD (OR = 2.25; 95% CI = 1.71-2.96) (metronidazole use in the year
before CD diagnosis: OR = 2.38; 95% CI = 1.78-3.19; and ≥ three courses of metronidazole:
OR = 1.90; 95% CI = 0.62-5.78). Use of metronidazole was similarly associated with small-
intestinal inflammation and normal mucosa but positive CD serology (Additional file 4).
To reduce the confounding effect of comorbidity we restricted our data to individuals with no
hospital admissions (CD: n = 2,047; controls: n = 12,069). However, this post-hoc analysis
revealed only a marginally changed OR for subsequent CD in relation to antibiotic use (OR =
1.30; 95% CI = 1.16 – 1.46). Post-hoc adjustment for number of outpatient visits before
biopsy slightly changed the OR for CD (OR = 1.19; 95% CI = 1.08-1.31). Further, antibiotic
use more than one year before biopsy examination was also associated with subsequent CD
(OR = 1.30; 95% CI = 1.08-1.56).
We also estimated the OR for subsequent CD based on use of any antibiotics during the first
six months of life. Only 3 of 16 (18.8%) children born after July 2005 and subsequently
diagnosed with CD had been exposed to any antibiotics during their first six months of life,
as compared with 7/80 (8.8%) children in the controls (OR = 2.26; 95% CI = 0.55-9.25).
Discussion
This is the first study to find a positive association between antibiotic use and subsequent CD.
Antibiotic exposure was also linked to small-intestinal inflammation and to normal mucosa
with positive CD serology, both of which may represent early CD. The consistent association
between the multiple groups, the slightly stronger association between repeated use of
antibiotics compared with no use as well as the association with use of certain antibiotics
(e.g., metronidazole) and CD may suggest that antibiotic exposure, possibly through a
changed gut microbiota, plays a pathogenic role in early CD development. However, given
the lack of time-response effect, within the limited time window studied, we cannot rule out
non-causal explanations for our findings.
Observational studies on drugs are particularly susceptible to the concerns of reverse
causation and confounding-by-indication. Reverse causation defines the causality bias if the
exposure is a response to manifestations of the undiagnosed disease. In CD it is difficult to
date the true onset of disease and thereby to establish whether antibiotic use truly preceded
CD or whether the antibiotic was given for the symptoms of as yet undiagnosed CD. Several
studies have shown a mean diagnostic delay of 5–11 years from onset of CD symptoms until
diagnosis, [27] a time associated with an increased number of consultation visits [28] and
possibly an increased likelihood of receiving antibiotic prescriptions. To reduce the risk of
reverse causation and the effect of comorbidity, which may act as a confounder by increasing
the possibility of receiving antibiotic prescriptions, we performed two post-hoc analyses
restricted to individuals exposed to antibiotics in the first six months of life or individuals
without hospital admission. Although these post-hoc analyses revealed largely unchanged
ORs, they do not rule out residual comorbidity or reverse causation.
12. Observational studies on drugs may also be subject to confounding-by-indication in which
the indication for treatment and not the treatment per se is associated with the outcome.
Individuals with undiagnosed CD have an increased risk of several diseases that may, in
concert, increase their likelihood to receive antibiotics [25]. For example, because antibiotics
are frequently misused in viral infections, [29] confounding may be introduced when
antibiotics are erroneously used to combat adenovirus or rotavirus infections, both proposed
as risk factors for CD development [2]. However, the Swedish Medical Products Agency do
not recommend antibiotic treatment in diarrhoeal illnesses, except for cases of severe
bacterial gastroenteritis [30]. Further, just as for diagnosed CD, undiagnosed CD may be
associated with bacterial infections, [31] which may have also influenced our results. Finally,
the fact that all three cohorts were similarly associated with antibiotic use raises the
possibility that an external factor, i.e. gastrointestinal symptoms such as diarrhoea, increases
the “risk” of both antibiotic use and the performance of a small bowel biopsy.
It is well-established that the intestinal microbiota influences the maturation of the intestinal
immune system [32]. Meanwhile several studies have found an imbalanced composition of
the intestinal microbiota in those with CD [33]. In vitro studies suggest that intestinal
dysbiosis may, in the presence of gliadin, increase intestinal epithelial permeability [10] and
enable epithelial translocation of gliadin peptides potentially triggering CD [2]. Other data
suggest that the distinct intestinal microbiota in CD may have pro-inflammatory properties
that affect the immune response elicited by gluten [34]. Although this study lacks conclusive
evidence for a causal association between antibiotic use and subsequent CD, our results do
not refute the hypothesis that the intestinal microbiota affects CD development. A causal
association may also be supported by the slightly stronger association to subsequent CD and
certain antibiotics (e.g., metronidazole) that have a major impact on the anaerobic bacteria of
the colon. Consequently, today’s prevalent use of antibiotics and their potential public heath
impact on CD development warrant attention in future research.
Antibiotic use has been associated with the development of several immunological diseases,
including inflammatory bowel disease [35] and asthma [36]. More importantly with regard to
CD, most [22,37] but not all studies, [38] have failed to find an association between antibiotic
use and subsequent type 1 diabetes, a disease that otherwise shares many aetiological traits
with CD [39].
A major strength of this study is our use of multiple groups on the CD spectrum (CD, small-
intestinal inflammation and normal mucosa with positive CD serology) [18]. With this study
design, we were able to examine the association of antibiotic treatment by the degree of
mucosal abnormality. Multiple groups also improved our evaluation of potential causality.
Another strength is the use of prospectively recorded exposure and outcome data, which
eliminate the risk of recall bias. Furthermore, this study provided detailed information on
antibiotic use, including time and age of exposure, type of antibiotics and number of courses.
The use of biopsy data enabled us to identify a representative population with CD. In
Sweden, more than 95% of gastroenterologists obtain a small-intestinal biopsy before CD
diagnosis [14], implying that biopsy records have a high sensitivity for diagnosed CD. We
regard the risk of misclassification in CD as low. In an earlier validation study 108 (95%) of
114 individuals with villous atrophy had CD [14]. Misclassification could be more of a
concern in inflammation because villous atrophy may be patchy and not all inflammation is
related to CD or to a pre-coeliac state. Furthermore, any potential misclassification of
13. histopathology should be non-differential regarding antibiotic use and therefore should not
lead to spurious associations, but to an underestimation of the true effect.
Our third cohort included individuals with normal small-intestinal mucosa, but positive CD
serology. Most of these individuals had a single positive AGA serology with a lower
specificity for CD than TTG or EMA. Thus, it may be argued that this condition does not
represent a pre-coeliac state. However, when Hill et al. reviewed 26 studies of CD serology,
they observed a median AGA specificity of 93% [40].
Antibiotic exposure was determined by the Swedish Prescribed Drug Register, which
includes nationwide high-quality data on all dispensed prescribed medications [19]. Self-
medication, i.e. obtaining an antibiotic without prescription, is very rare in Sweden, estimated
to be 0.3% of all antibiotics used [41]. A limitation of our study is the recent start of the
Swedish Prescribed Drug Register (established in July 2005) and the left truncation of
exposure data in which individuals diagnosed with CD early in the study period (and their
matched controls) will have little chance of being classified as antibiotic users because of
lack of antibiotic data before July 2005. However, this loss of prior antibiotic data should not
be differentially related to future CD status, and therefore only bias our results toward the
null.
Conclusions
In conclusion, we found a positive association between antibiotic use and subsequent CD, as
well as with inflammation, and with having a normal mucosa but positive CD serology. One
explanation could be that antibiotic exposure, possibly through changes in the gut microbiota,
plays a role in early CD development, but non-causal explanations cannot be ruled out.
Within the limited time window studied, the lack of a time-response effect raises the
possibility of reverse causation, in particular, prescription of antibiotics to individuals with
manifestations of undiagnosed CD.
Abbreviations
ATC, Anatomical therapeutic chemical (pharmaceutical classification); AGA, Antigliadin
antibody; CD, Coeliac disease; CI, Confidence interval; EMA, Endomysial antibody; OR,
Odds ratio; TTG, Tissue transglutaminase antibody
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
ICMJE criteria for authorship read and met: KM, WY; BL; PG; MB; TC; JFL. Agree with the
manuscript’s results and conclusions: KM, WY; BL; PG; MB; TC; JFL. Designed the
experiments/the study: KM, JFL. Collected data: JFL. Analyzed the data: KM. Wrote the first
draft of the paper: KM. Contributed to the writing of the paper: WY; BL; PG; MB; TC; JFL.
Contributed to the design of the study and interpretation of the data analyses: WY; BL; PG;
MB; TC. Interpretation of data; approved the final version of the manuscript: KM, WY; BL;
14. PG; MB; TC; JFL. Responsible for data integrity: KM, JFL. Supervised the project including
data analyses: JFL. Obtained funding: JFL. All auhtors read and approved the final
manuscript.
Acknowledgements
This work was supported by: The American Scandinavian Foundation [BL], the Celiac Sprue
Association [BL, JFL], and the National Center for Research Resources, a component of the
National Institutes of Health (grant number: KL2 RR024157) [BL]; National Institutes of
Health (grant number: R01DK090989) [MB], and the Diane Belfer Program for Human
Microbial Ecology [MB]; The Swedish Society of Medicine [JFL], the Swedish Research
Council [JFL], the Sven Jerring Foundation [JFL], the Örebro Society of Medicine [JFL], the
Karolinska Institutet [JFL], the Clas Groschinsky Foundation [JFL], the Juhlin Foundation
[JFL], the Majblomman Foundation [JFL] and the Uppsala-Örebro Regional Research
Council [JFL]. The funders had no role in study design, data collection and analysis, decision
to publish, or preparation of the manuscript.
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Additional files
Additional_file_1 as PDF
Additional file 1 Anatomical therapeutic chemical codes used to classify systemic antibiotics
(J01).
Additional_file_2 as PDF
Additional file 2 Odds ratios for prior antibiotic use in individuals with normal mucosa and
positive coeliac disease serology. Odds ratios (ORs) for prior antibiotic use with adjustment
for education level.
Additional_file_3 as PDF
Additional file 3 Odds ratios for prior antibiotic use in individuals with coeliac disease,
small-intestinal inflammation, and normal small-intestinal mucosa a
. Stratified analyses by
age at biopsy. Odds ratios for prior antibiotic use in individuals with coeliac disease.
Stratified analyses by year of diagnosis.
Additional_file_4 as PDF
Additional file 4 Odds ratio for prior use of metronidazole in individuals with small-
intestinal inflammation and normal mucosaa
.