Chronic Airflow Obstruction Briefing: Technical Documentation

Chronic airflow obstruction (CAO) is a chronic lung condition that interferes with normal breathing. CAO includes chronic obstructive pulmonary disease (COPD), chronic bronchitis and emphysema. IPH has systematically estimated and forecast the prevalence of CAO on the island of Ireland. This document details the methods used to calculate these estimates and forecasts.

Liver kidney microsomes type 1 antibodies are associated with 80% reduction of the CYP2D6 activity in patients with chronic hepatitis C

Introduction Liver kidney microsomal type 1 (LKM-1) antibodies have been shown to decrease CYP2D6 activity in vitro. We investigated whether LKM-1 antibodies might reduce CYP2D6 activity also in vivo.Materials and Methods All patients with chronic hepatitis C and LKM-1 antibodies enrolled in the Swiss Hepatitis C Cohort Study (SCCS) were assessed: ten were eligible and fi tted to patients without LKM-1 antibodies. Patients were genotyped for CYP2D6 variants to exclude individuals with a poor metabolizer genotype. CYP2D6 activity was measured by a specifi c substrate using the dextromethorphan/dextrorphan (DEM/DOR) metabolic ratio to classify patients into four activity phenotypes (i.e. ultrarapid, extensive, intermediate and poor metabolizers). The concordance between phenotype based on DEM/DOR ratio and phenotype expected from genotype was examined in LKM-1 positive and negative patients. Groups were compared with respect to the DEM/DOR metabolic ratio.Results All patients had a CYP2D6 extensive metabolizer genotype. The observed phenotype was concordant with CYP2D6 genotype in most LKM-negative patients, whereas only three (30%) LKM-1 positive patients had a concordant phenotype (six presented an intermediate and one a poor metabolizer phenotype). The median DEM/DOR ratio was six-fold higher in LKM-1 positive than in LKM-1 negative patients (0.096 vs. 0.016, p = 0.004), indicating that CYP2D6 metabolic function was significantly reduced in the presence of LKM-1 antibodies.Conclusion In chronic hepatitis C patients with LKM-1 antibodies, the CYP2D6 metabolic activity was on average reduced by 80%. The impact of LKM-1 antibodies on CYP2D6-mediated drug metabolism pathways warrants further translational studies in the setting of new protease inhibitor therapies

Risk of death due to chronic chagasic cardiopathy

In this longitudinal study 5,710 people were included. The inclusion criteria were two positive serological results for Trypanosoma cruzi infection, 15 and 50 years old and no other demostrable diesease at the time of study. In the five year follow up 1,117 patients were lost. The follow up involved yearly evaluation of serology, clinical examination, X-ray of torax, and ECG, for 4,593 patients and 263 were contacted at home because they did not assist for their clinical consultant. Time average of follow up was 5.3 years. Eighty nine (1.5%) of the 4,593 patients died during the follow-up period, 63 (71%) by cardiac insufiency (CI) and 26 (29%) by severe ventricular arrithmias. Diagnosis of cardiomegaly was present in all the patients with diagnosis of CI and in 15 (5%) of the patients with diagnosis of arrithmias.The ECG alterations of these pacients show 61 right bundle brunch block (RBBB), associated or not with left anterior hemiblock (LAHB), 47 pathological Q wave and 70 primary repolarization alterations; 61 had polyfocal ventricular arrithmia. The death rate was similar in the sexes and was more frequent between 40 and 50 years of age. Information on 1,380 recuperated patients shows that 15 died with no previous symptoms and without medical assistance and were interpretate as sudden death. The latest ECG in three follow-up of these pacients indicates (before death) that only one had normal study and 14 presented 12 RBBB; 9 LAHB; 7 isolated ventricular arrithmia; 10 repolariz alterations; 2 patological Q wave, 10 patients of them with RBBB and repolariz alterations. In all the cases we had people between 35 and 43 years old, 9 men and 6 women. This study shows that in Chagas disease is possible to differenciate two risk groups. A low risk death group that have normal ECG and clinical evaluation during the follow up, and a high risk group associate ECG with RBBB and primary alterations of repolarization and/or inactivation zones with not anual clinical evaluation.

IPH response to a Draft Policy Framework for supporting people in Northern Ireland living with long term (or chronic) conditions

The Department of Health, Social Services and Public Safety recently consulted on a draft Policy Framework for supporting people in Northern Ireland living with long term (or chronic) conditions

Prevalence of chronic conditions – Hypertension

IPH has estimated and forecast clinical diagnosis rates of hypertension among adults for the years 2010, 2015 and 2020. In the Republic of Ireland, the data are based on the Survey of Lifestyle, Attitudes and Nutrition (SLÁN) 2007. The data describe the number of people who report that they have experienced doctor-diagnosed hypertension in the previous 12 months (annual clinical diagnosis). Data are available by age and sex for each Local Health Office of the Health Service Executive (HSE) in the Republic of Ireland. In Northern Ireland, the data is based on the Health and Social Wellbeing Survey 2005/06. The data describe the number of people who report that they have experienced doctor/nurse-diagnosed hypertension at any time in the past (lifetime clinical diagnosis). Data are available by age and sex for each Local Government District in Northern Ireland. Clinical diagnosis rates in the Republic of Ireland relate to the previous 12 months and are not directly comparable with clinical diagnosis rates in Northern Ireland which relate to anytime in the past.   The IPH estimated prevalence per cents may be marginally different to estimated prevalence per cents taken directly from the reference study. There are two reasons for this: 1) The IPH prevalence estimates relate to 2010 while the reference studies relate to earlier years (Northern Ireland Health and Social Wellbeing Survey 2005/06, Survey of Lifestyle, Attitudes and Nutrition 2007, Understanding Society 2009). Although we assume that the risk of the condition in the risk groups do not change over time, the distribution of the number of people in the risk groups in the population changes over time (eg the population ages).  This new distribution of the risk groups in the population means that the risk of the condition is weighted differently to the reference study and this results in a different overall prevalence estimate. 2) The IPH prevalence estimates are based on a statistical model of the reference study. The model includes a number of explanatory variables to predict the risk of the condition. Therefore the model does not include records from the reference study that are missing data on these explanatory variables. A prevalence estimate for a condition taken directly from the reference study would include these records.

Prevalence of chronic conditions – Coronary Heart Disease

IPH has estimated and forecast clinical diagnosis rates of CHD (heart attack and/or angina) among adults for the years 2010, 2015 and 2020. In the Republic of Ireland, the data are based on the Survey of Lifestyle, Attitudes and Nutrition (SLÁN) 2007 . The data describe the number of people who report that they have experienced doctor-diagnosed heart attack and/or angina in the previous 12 months (annual clinical diagnosis). Data is available by age and sex for each Local Health Office of the Health Service Executive (HSE) in the Republic of Ireland. In Northern Ireland, the data are based on the Health and Social Wellbeing Survey 2005/06 . The data describe the number of people who report that they have experienced doctor-diagnosed heart attack and/or angina at any time in the past (lifetime clinical diagnosis). Data are available by age and sex for each Local Government District in Northern Ireland. Clinical diagnosis rates in the Republic of Ireland relate to the previous 12 months and are not directly comparable with clinical diagnosis rates in Northern Ireland which relate to anytime in the past. The IPH estimated prevalence per cents may be marginally different to estimated prevalence per cents taken directly from the reference study. There are two reasons for this: 1) The IPH prevalence estimates relate to 2010 while the reference studies relate to earlier years (Northern Ireland Health and Social Wellbeing Survey 2005/06, Survey of Lifestyle, Attitudes and Nutrition 2007, Understanding Society 2009). Although we assume that the risk of the condition in the risk groups do not change over time, the distribution of the number of people in the risk groups in the population changes over time (eg the population ages).  This new distribution of the risk groups in the population means that the risk of the condition is weighted differently to the reference study and this results in a different overall prevalence estimate. 2) The IPH prevalence estimates are based on a statistical model of the reference study. The model includes a number of explanatory variables to predict the risk of the condition. Therefore the model does not include records from the reference study that are missing data on these explanatory variables. A prevalence estimate for a condition taken directly from the reference study would include these records.

Prevalence of chronic conditions – Chronic Airflow Obstruction

IPH has estimated and forecast clinical diagnosis rates of CAO among adults for the years 2010, 2015 and 2020. In the Republic of Ireland, the data are based on the Survey of Lifestyle, Attitudes and Nutrition (SLÁN) 2007. The data describe the number of people who report that they have experienced doctor-diagnosed chronic bronchitis, chronic obstructive lung (pulmonary) disease, or emphysema in the previous 12 months (annual clinical diagnosis). Data is available by age and sex for each Local Health Office of the Health Service Executive (HSE) in the Republic of Ireland. In Northern Ireland, the data are based on the Health and Social Wellbeing Survey 2005/06. The data describe the number of people who report that they have experienced doctor-diagnosed COPD or chronic obstructive pulmonary disease eg chronic bronchitis / emphysema or both disorders at any time in the past (lifetime clinical diagnosis). Data are available by age and sex for each Local Government District in Northern Ireland. Clinical diagnosis rates in the Republic of Ireland relate to the previous 12 months and are not directly comparable with clinical diagnosis rates in Northern Ireland which relate to anytime in the past.   The IPH estimated prevalence per cents may be marginally different to estimated prevalence per cents taken directly from the reference study. There are two reasons for this: 1) The IPH prevalence estimates relate to 2010 while the reference studies relate to earlier years (Northern Ireland Health and Social Wellbeing Survey 2005/06, Survey of Lifestyle, Attitudes and Nutrition 2007, Understanding Society 2009). Although we assume that the risk of the condition in the risk groups do not change over time, the distribution of the number of people in the risk groups in the population changes over time (eg the population ages).  This new distribution of the risk groups in the population means that the risk of the condition is weighted differently to the reference study and this results in a different overall prevalence estimate. 2) The IPH prevalence estimates are based on a statistical model of the reference study. The model includes a number of explanatory variables to predict the risk of the condition. Therefore the model does not include records from the reference study that are missing data on these explanatory variables. A prevalence estimate for a condition taken directly from the reference study would include these records.

Prevalence of chronic conditions – Musculoskeletal Conditions

IPH has estimated and forecast the number of adults with MSCs for the years 2010, 2015 and 2020. In the Republic of Ireland, the data are based on the Survey of Lifestyle, Attitudes and Nutrition (SLÁN) 2007 . The data describe the number of people who report that they have experienced doctor-diagnosed MSC in the previous 12 months:     Lower back pain or any other chronic back condition     Rheumatoid arthritis (inflammation of the joints)     Osteoarthritis (arthrosis, joint degradation) Data are  available by age and sex for each Local Health Office of the Health Service Executive (HSE) in the Republic of Ireland. In Northern Ireland, the data are based on the Health and Social Wellbeing Survey 2005/06 and Understanding Society 2009. The data describe the number of adults who:     Have ever consulted a doctor about back pain     Are currently receiving treatment for musculoskeletal problems (such as arthritis, rheumatism)     Have ever been told by a doctor or other health professional that they had have arthritis? Data are available by age and sex for each Local Government District in Northern Ireland. There are significant differences between the definitions used in RoI and NI and North-South comparisons are not valid. The RoI measures relate to specific MSCs in the previous 12 months that had been diagnosed by a doctor. The NI measures relate to doctor-consultations at any time in the past, doctor-diagnosis at any time in the past and current treatment. The IPH estimated prevalence per cents may be marginally different to estimated prevalence per cents taken directly from the reference study. There are two reasons for this: 1) The IPH prevalence estimates relate to 2010 while the reference studies relate to earlier years (Northern Ireland Health and Social Wellbeing Survey 2005/06, Survey of Lifestyle, Attitudes and Nutrition 2007, Understanding Society 2009). Although we assume that the risk of the condition in the risk groups do not change over time, the distribution of the number of people in the risk groups in the population changes over time (eg the population ages).  This new distribution of the risk groups in the population means that the risk of the condition is weighted differently to the reference study and this results in a different overall prevalence estimate. 2) The IPH prevalence estimates are based on a statistical model of the reference study. The model includes a number of explanatory variables to predict the risk of the condition. Therefore the model does not include records from the reference study that are missing data on these explanatory variables. A prevalence estimate for a condition taken directly from the reference study would include these records.

Frequency of specific anti-Toxoplasma gondii IgM, IgA and IgE in Colombian patients with acute and chronic ocular toxoplasmosis

We studied the frequency of specific anti-Toxoplasma IgM, IgA and IgE antibodies in serum of 28 immunocompetent Colombian patients, selected by ophthalmologists and with lesions that were compatible with ocular toxoplasmosis. Patients were classified in three groups: (i) group 1 consisted of ten patients with a first episode; (ii) group 2, with seven patients with a recurrence and (iii) group 3, consisted of eleven patients with chronic chorioretinal lesion without uveitis. We found that 10/28 (35%) of Colombian patients with ocular toxoplasmosis possessed at least one serological marker for Toxoplasma infection different from IgG. In group 1 (first episode), we found simultaneous presence of specific IgM plus IgA plus IgE in 1/10 (10%). In group 2 (recurrences) in 1/7 (14%) we found IgM and IgA test positives and in 1/7 (14%) we found IgM and IgE tests positives. In group 3 (toxoplasmic chorioretinal scar) the IgA serological test was positive in 2/11 (18%). These results show that serum IgM or IgA or IgE can be present during recurrences.

Experimental toxoplasmosis in Balb/c mice. Prevention of vertical disease transmission by treatment and reproductive failure in chronic infection

In a study of congenital transmission during acute infection of Toxoplasma gondii, 23 pregnant Balb/c mice were inoculated orally with two cysts each of the P strain. Eight mice were inoculated 6-11 days after becoming pregnant (Group 1). Eight mice inoculated on the 10th-15th day of pregnancy (Group 2) were treated with 100 mg/kg/day of minocycline 48 h after inoculation. Seven mice inoculated on the 10th-15th day of pregnancy were not treated and served as a control (Group 3). Congenital transmission was evaluated through direct examination of the brains of the pups or by bioassay and serologic tests. Congenital transmission was observed in 20 (60.6%) of the 33 pups of Group 1, in one (3.6%) of the 28 pups of Group 2, and in 13 (54.2%) of the 24 pups of Group 3. Forty-nine Balb/c mice were examined in the study of congenital transmission of T. gondii during chronic infection. The females showed reproductive problems during this phase of infection. It was observed accentuated hypertrophy of the endometrium and myometrium. Only two of the females gave birth. Our results demonstrate that Balb/c mice with acute toxoplasmosis can be used as a model for studies of congenital T. gondii infection. Our observations indicate the potential of this model for testing new chemotherapeutic agents against congenital toxoplasmosis.

Treatment of chronic hepatitis C genotype 1 with triple therapy comprising telaprevir or boceprevir.

Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. Two first-generation protease inhibitors, telaprevir and boceprevir, have recently been approved for the treatment of chronic hepatitis C genotype 1. Triple therapy comprising pegylated interferon-α, ribavirin and telaprevir or boceprevir increases sustained virological response rates to ~70% and allows to shorten treatment duration in ~½ of treatment-naïve patients with chronic hepatitis C genotype 1. Sustained virological response rates in treatment-experienced patients depend on the response to previous treatment, ranging from >80% in previous relapsers to ~30% in previous null responders. These advances come at the expense of new adverse effects and increased cost. In addition, treatment of chronic hepatitis C will become more complex. In these times of changing medical practice, the present expert opinion statement by the Swiss Association for the Study of the Liver shall provide guidance on the treatment of chronic hepatitis C with triple therapy comprising telaprevir or boceprevir.

The adolescent with a chronic condition. Part II: healthcare provision.

The treatment and management of chronic conditions during adolescence pose specific issues that need to be appropriately handled by health professionals. In this paper, questions related to disclosure of the diagnosis, the management of adherence to therapy, the need for an interdisciplinary network approach, lifestyles' anticipatory guidance and prevention, and the transition into an adult healthcare setting are reviewed. Special areas such as the issue of life threatening diseases and the ethical aspects of the treatment of chronic conditions are also discussed.