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Sample records for danish clinical cohort

  1. Danish cohort of monozygotic inflammatory bowel disease twins: Clinical characteristics and inflammatory activity

    PubMed Central

    Moller, Frederik Trier; Knudsen, Lina; Harbord, Marcus; Satsangi, Jack; Gordon, Hannah; Christiansen, Lene; Christensen, Kaare; Jess, Tine; Andersen, Vibeke

    2016-01-01

    AIM: To describe the establishment of a Danish inflammatory bowel diseases (IBD) twin cohort with focus on concordance of treatment and inflammatory markers. METHODS: We identified MZ twins, likely to be discordant or concordant for IBD, by merging information from the Danish Twin Register and the National Patient Register. The twins were asked to provide biological samples, questionnaires, and data access to patient files and public registries. Biological samples were collected via a mobile laboratory, which allowed for immediate centrifugation, fractionation, and storage of samples. The mean time from collection of samples to storage in the -80 °C mobile freezer was less than one hour. The diagnoses where validated using the Copenhagen diagnostic criteria. RESULTS: We identified 159 MZ IBD twin pairs, in a total of 62 (39%) pairs both twins agreed to participate. Of the supposed 62 IBD pairs, the IBD diagnosis could be confirmed in 54 pairs. The cohort included 10 concordant pairs, whereof some were discordant for either treatment or surgery. The 10 concordant pairs, where both pairs suffered from IBD, included eight CD/CD pairs, one UC/UC pair and one UC/IBDU pair. The discordant pairs comprised 31 UC, 5 IBDU (IBD unclassified), and 8 CD discordant pairs. In the co-twins not affected by IBD, calprotectin was above 100 μg/g in 2 participants, and above 50 μg/g in a further 5 participants. CONCLUSION: The presented IBD twin cohorts are an excellent resource for bioinformatics studies with proper adjustment for disease-associated exposures including medication and inflammatory activity in the co-twins. PMID:27275097

  2. Clinical features of Clostridium difficile infection and molecular characterization of the isolated strains in a cohort of Danish hospitalized patients.

    PubMed

    Søes, L M; Brock, I; Persson, S; Simonsen, J; Pribil Olsen, K E; Kemp, M

    2012-02-01

    The purpose of this study was to compare clinical features of Clostridium difficile infection (CDI) to toxin gene profiles of the strains isolated from Danish hospitalized patients. C. difficile isolates were characterized by PCR based molecular typing methods including toxin gene profiling and analysis of deletions and truncating mutations in the toxin regulating gene tcdC. Clinical features were obtained by questionnaire. Thirty percent of the CDI cases were classified as community-acquired. Infection by C. difficile with genes encoding both toxin A, toxin B and the binary toxin was significantly associated with hospital-acquired/healthcare-associated CDI compared to community-acquired CDI. Significantly higher leukocyte counts and more severe clinical manifestations were observed in patients infected by C. difficile containing genes also encoding the binary toxin together with toxin A and B compared to patients infected by C. difficile harbouring only toxin A and B. In conclusion, infection by C. difficile harbouring genes encoding both toxin A, toxin B and the binary toxin were associated with hospital acquisition, higher leukocyte counts and severe clinical disease. PMID:21744281

  3. Residential Radon and Brain Tumour Incidence in a Danish Cohort

    PubMed Central

    Bräuner, Elvira V.; Andersen, Zorana J.; Andersen, Claus E.; Pedersen, Camilla; Gravesen, Peter; Ulbak, Kaare; Hertel, Ole; Loft, Steffen; Raaschou-Nielsen, Ole

    2013-01-01

    Background Increased brain tumour incidence over recent decades may reflect improved diagnostic methods and clinical practice, but remain unexplained. Although estimated doses are low a relationship between radon and brain tumours may exist. Objective To investigate the long-term effect of exposure to residential radon on the risk of primary brain tumour in a prospective Danish cohort. Methods During 1993–1997 we recruited 57,053 persons. We followed each cohort member for cancer occurrence from enrolment until 31 December 2009, identifying 121 primary brain tumour cases. We traced residential addresses from 1 January 1971 until 31 December 2009 and calculated radon concentrations at each address using information from central databases regarding geology and house construction. Cox proportional hazards models were used to estimate incidence rate-ratios (IRR) and 95% confidence intervals (CI) for the risk of primary brain tumours associated with residential radon exposure with adjustment for age, sex, occupation, fruit and vegetable consumption and traffic-related air pollution. Effect modification by air pollution was assessed. Results Median estimated radon was 40.5 Bq/m3. The adjusted IRR for primary brain tumour associated with each 100 Bq/m3 increment in average residential radon levels was 1.96 (95% CI: 1.07; 3.58) and this was exposure-dependently higher over the four radon exposure quartiles. This association was not modified by air pollution. Conclusions We found significant associations and exposure-response patterns between long-term residential radon exposure radon in a general population and risk of primary brain tumours, adding new knowledge to this field. This finding could be chance and needs to be challenged in future studies. PMID:24066143

  4. Survival in familial colorectal cancer: a Danish cohort study.

    PubMed

    Lautrup, Charlotte Kvist; Mikkelsen, Ellen M; Lash, Timothy L; Katballe, Niels; Sunde, Lone

    2015-12-01

    The monogenic Lynch syndrome (LS) is associated with better survival in colorectal cancer (CRC) patients. Whether family history of CRC affects CRC prognosis in general remains unclear. We evaluated overall mortality in a Danish cohort of CRC patients comparing patients with a family history (FHpos) to those without (FHneg) with focus on patients from non-syndromic families, thus FHpos patients were further divided into a non-syndromic group (FHNS) and a HNPCC/LS group (FHHNPCC). We included CRC patients diagnosed 1995-1998. First degree relatives were identified using Danish population registries and family history was obtained by linkage to Danish medical registries. 1- and 5-year mortality were evaluated using the Kaplan-Meier method and Cox regression, with adjustment for age, sex, cancer site, cancer stage, and comorbidity. 1196 CRC patients were included in the study, 219 FHpos patients of whom 197 were FHNS patients. 1- and 5-year adjusted Mortality Rate Ratios comparing FHpos patients to FHneg patients were 0.99 (95% CI 0.69, 1.42) and 1.07 (95% CI 0.87, 1.32), respectively. For FHNS patients, the corresponding MRRs were 1.01 (95% CI 0.69, 1.47) and 1.15 (95% CI 0.93, 1.43). For the FHHNPCC patients MRRs were 0.84 (95% CI 0.29, 2.44) and 0.66 (95% CI 0.33, 1.31), respectively. In contrast to the lower mortality in LS patients, other types of familial CRC do not seem to affect the survival after CRC diagnosis. PMID:25963853

  5. Residential radon and lung cancer incidence in a Danish cohort

    SciTech Connect

    Braeuner, Elvira V.; Andersen, Claus E.; Sorensen, Mette; Jovanovic Andersen, Zorana; Gravesen, Peter; Ulbak, Kaare; Hertel, Ole; Pedersen, Camilla; Overvad, Kim; Tjonneland, Anne; Raaschou-Nielsen, Ole

    2012-10-15

    High-level occupational radon exposure is an established risk factor for lung cancer. We assessed the long-term association between residential radon and lung cancer risk using a prospective Danish cohort using 57,053 persons recruited during 1993-1997. We followed each cohort member for cancer occurrence until 27 June 2006, identifying 589 lung cancer cases. We traced residential addresses from 1 January 1971 until 27 June 2006 and calculated radon at each of these addresses using information from central databases regarding geology and house construction. Cox proportional hazards models were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI) for lung cancer risk associated with residential radon exposure with and without adjustment for sex, smoking variables, education, socio-economic status, occupation, body mass index, air pollution and consumption of fruit and alcohol. Potential effect modification by sex, traffic-related air pollution and environmental tobacco smoke was assessed. Median estimated radon was 35.8 Bq/m{sup 3}. The adjusted IRR for lung cancer was 1.04 (95% CI: 0.69-1.56) in association with a 100 Bq/m{sup 3} higher radon concentration and 1.67 (95% CI: 0.69-4.04) among non-smokers. We found no evidence of effect modification. We find a positive association between radon and lung cancer risk consistent with previous studies but the role of chance cannot be excluded as these associations were not statistically significant. Our results provide valuable information at the low-level radon dose range.

  6. Social Origin and Graduation Age: A Cohort Comparison of Danish University Students

    ERIC Educational Resources Information Center

    Klausen, Trond Beldo

    2016-01-01

    This paper investigates whether social origin has an impact on graduation age among university students. A large number of social background factors are applied on a large data set of 4 successive cohorts of Danish university graduates born 1960-1975. These are cohorts for whom university attendance increased steeply. Contrary to recent findings…

  7. Infertility, infertility treatment, and congenital malformations: Danish national birth cohort

    PubMed Central

    Zhu, Jin Liang; Basso, Olga; Obel, Carsten; Bille, Camilla; Olsen, Jørn

    2006-01-01

    Objectives To examine whether infertile couples (with a time to pregnancy of > 12 months), who conceive naturally or after treatment, give birth to children with an increased prevalence of congenital malformations. Design Longitudinal study. Setting Danish national birth cohort. Participants Three groups of liveborn children and their mothers: 50 897 singletons and 1366 twins born of fertile couples (time to pregnancy ≤ 12 months), 5764 singletons and 100 twins born of infertile couples who conceived naturally (time to pregnancy > 12 months), and 4588 singletons and 1690 twins born after infertility treatment. Main outcome measures Prevalence of congenital malformations determined from hospital discharge diagnoses. Results Compared with singletons born of fertile couples, singletons born of infertile couples who conceived naturally or after treatment had a higher prevalence of congenital malformations—hazard ratios 1.20 (95% confidence interval 1.07 to 1.35) and 1.39 (1.23 to 1.57). The overall prevalence of congenital malformations increased with increasing time to pregnancy. When the analysis was restricted to singletons born of infertile couples, babies born after treatment had an increased prevalence of genital organ malformations (hazard ratio 2.32, 1.24 to 4.35) compared with babies conceived naturally. No significant differences existed in the overall prevalence of congenital malformations among twins. Conclusions Hormonal treatment for infertility may be related to the occurrence of malformations of genital organs, but our results suggest that the reported increased prevalence of congenital malformations seen in singletons born after assisted reproductive technology is partly due to the underlying infertility or its determinants. The association between untreated infertility and congenital malformations warrants further examination. PMID:16893903

  8. Alcohol consumption and fecundability: prospective Danish cohort study

    PubMed Central

    Riis, Anders H; Wise, Lauren A; Hatch, Elizabeth E; Rothman, Kenneth J; Cueto, Heidi T; Sørensen, Henrik Toft

    2016-01-01

    Objective To investigate to what extent alcohol consumption affects female fecundability. Design Prospective cohort study. Setting Denmark, 1 June 2007 to 5 January 2016. Participants 6120 female Danish residents, aged 21-45 years, in a stable relationship with a male partner, who were trying to conceive and not receiving fertility treatment. Main outcome measures Alcohol consumption was self reported as beer (330 mL bottles), red or white wine (120 mL glasses), dessert wine (50 mL glasses), and spirits (20 mL) and categorized in standard servings per week (none, 1-3, 4-7, 8-13, and ≥14). Participants contributed menstrual cycles at risk until the report of pregnancy, start of fertility treatment, loss to follow-up, or end of observation (maximum 12 menstrual cycles). A proportional probability regression model was used to estimate fecundability ratios (cycle specific probability of conception among exposed women divided by that among unexposed women). Results 4210 (69%) participants achieved a pregnancy during follow-up. Median alcohol intake was 2.0 (interquartile range 0-3.5) servings per week. Compared with no alcohol consumption, the adjusted fecundability ratios for alcohol consumption of 1-3, 4-7, 8-13, and 14 or more servings per week were 0.97 (95% confidence interval 0.91 to 1.03), 1.01 (0.93 to 1.10), 1.01 (0.87 to 1.16) and 0.82 (0.60 to 1.12), respectively. Compared with no alcohol intake, the adjusted fecundability ratios for women who consumed only wine (≥3 servings), beer (≥3 servings), or spirits (≥2 servings) were 1.05 (0.91 to1.21), 0.92 (0.65 to 1.29), and 0.85 (0.61 to 1.17), respectively. The data did not distinguish between regular and binge drinking, which may be important if large amounts of alcohol are consumed during the fertile window. Conclusion Consumption of less than 14 servings of alcohol per week seemed to have no discernible effect on fertility. No appreciable difference in fecundability was observed by level of

  9. In-Utero Exposure to Bereavement and Offspring IQ: A Danish National Cohort Study

    PubMed Central

    Virk, Jasveer; Obel, Carsten; Li, Jiong; Olsen, Jørn

    2014-01-01

    Background Intelligence is a life-long trait that has strong influences on lifestyle, adult morbidity and life expectancy. Hence, lower cognitive abilities are therefore of public health interest. Our primary aim was to examine if prenatal bereavement measured as exposure to death of a close family member is associated with the intelligence quotient (IQ) scores at 18-years of age of adult Danish males completing a military cognitive screening examination. Methods We extracted records for the Danish military screening test and found kinship links with biological parents, siblings, and maternal grandparents using the Danish Civil Registration System (N = 167,900). The prenatal exposure period was defined as 12 months before conception until birth of the child. We categorized children as exposed in utero to severe stress (bereavement) during prenatal life if their mothers lost an elder child, husband, parent or sibling during the prenatal period; the remaining children were included in the unexposed cohort. Mean score estimates were adjusted for maternal and paternal age at birth, residence, income, maternal education, gestational age at birth and birth weight. Results When exposure was due to death of a father the offsprings' mean IQ scores were lower among men completing the military recruitment exam compared to their unexposed counterparts, adjusted difference of 6.5 standard IQ points (p-value = 0.01). We did not observe a clinically significant association between exposure to prenatal maternal bereavement caused by death of a sibling, maternal uncle/aunt or maternal grandparent even after stratifying deaths only due to traumatic events. Conclusion We found maternal bereavement to be adversely associated with IQ in male offspring, which could be related to prenatal stress exposure though more likely is due to changes in family conditions after death of the father. This finding supports other literature on maternal adversity during fetal life and cognitive

  10. HLA Associations and Risk of Posttransplant Lymphoproliferative Disorder in a Danish Population-Based Cohort

    PubMed Central

    Vase, Maja Ølholm; Maksten, Eva Futtrup; Strandhave, Charlotte; Søndergaard, Esben; Bendix, Knud; Hamilton-Dutoit, Stephen; Andersen, Claus; Møller, Michael Boe; Sørensen, Søren Schwartz; Kampmann, Jan; Eiskjær, Hans; Iversen, Martin; Weinreich, Ilse Duus; Møller, Bjarne; Jespersen, Bente; d'Amore, Francesco

    2015-01-01

    Background Posttransplant lymphoproliferative disorder (PTLD) is a feared complication to organ transplantation, associated with substantial morbidity and inferior survival. Risk factors for PTLD include T cell–depleting induction therapy and primary infection or reactivation of Epstein-Barr virus. Possible associations between certain HLA types and the risk of developing PTLD have been reported by other investigators; however, results are conflicting. Methods We conducted a retrospective, population-based study on 4295 Danish solid organ transplant patients from the Scandiatransplant database. Having identified 93 PTLD patients in the cohort, we investigated the association of HLA types with PTLD, Epstein-Barr virus status and time to PTLD onset. The outcomes survival and PTLD were evaluated using Cox regression; mismatching, and the PTLD-specific mortality were evaluated in a competing risk analysis. Results Risk of PTLD was associated with male sex (odds ratio, 1.70; 95% confidence interval, 1.07-2.71), and, in women, HLA-DR13 conferred an increased risk (odds ratio, 3.22; 95% confidence interval, 1.41-7.31). In multivariate analysis, HLA-B45 and HLA-DR13 remained independent predictive factors of PTLD. Mismatching in the B locus was associated with a reduced risk of PTLD (P < 0.001). Overall survival was poor after a PTLD diagnosis and was significantly worse than that in the remaining transplant cohort (P < 0.001). Conclusions Our data indicate risk-modifying HLA associations, which can be clinically useful after transplantation in personalized monitoring schemes. Given the strong linkage disequilibrium in the HLA region, the associations must be interpreted carefully. The large size, virtually complete ascertainment of cases and no loss to follow-up remain important strengths of the study. PMID:27500227

  11. Revitalising the Metropolit 1953 Danish male birth cohort: background, aims and design.

    PubMed

    Osler, Merete; Andersen, Anne-Marie Nybo; Lund, Rikke; Batty, G David; Hougaard, Charlotte Ørsted; Damsgaard, Mogens Trab; Due, Pernille; Holstein, Bjørn E

    2004-09-01

    Recent research indicates that factors operating during childhood are related to adult health. Thus, longitudinal studies with information on subsequent phases may be key to understanding later health outcomes. The main objective of this paper is to describe the history and design of a Danish birth cohort, and its revitalisation. In 1965, information from birth certificates for 11 591 of a total of 12 270 males born in 1953 in the Metropolitan area of Copenhagen, Denmark were traced. These boys were the study population of a sociological investigation conducted with the aim of describing social mobility. At age 12 years, 9537 of these cohort members completed a questionnaire in school, which included cognitive measures and information on social aspirations and leisure time activities. In 1966 educational performance tests were administered for these boys and, in 1968, mothers of 2890 cohort members were interviewed regarding family social backgrounds. With the establishment of the Civil Registration System (CRS) in 1968, it was possible to identify 11 532 cohort members. In 2002 we began the process of revitalising this study with the aim of investigating the influence of early life factors on later health. We succeeded in ascertaining the vital status of all subjects in the CRS. This showed that 863 subjects had died between 1968 and 2002. Linkages to the Register of Causes of Death, the National Hospital Register, Psychiatric Central Register and Danish Cancer Registry have been completed. In total, 7969 cohort members had been hospitalised for any somatic illness and, according to the Psychiatric Central Register, 1382 men had been admitted to a psychiatric hospital or ward. In the Cancer Registry we found 363 of our study participants. Analyses exploring the influence of social conditions in early life, birth dimensions, and childhood cognition on adult health experience are at various stages of completion. A questionnaire-based postal follow-up survey is

  12. Risk of Diabetes Mellitus in Persons with and without HIV: A Danish Nationwide Population-Based Cohort Study

    PubMed Central

    Rasmussen, Line D.; Mathiesen, Elisabeth R.; Kronborg, Gitte; Pedersen, Court; Gerstoft, Jan; Obel, Niels

    2012-01-01

    Objective In a nationwide, population-based cohort study we assessed the risk of diabetes mellitus (DM) in HIV-infected individuals compared with the general population, and evaluated the impact of risk factors for DM in HIV-infected individuals. Methods We identified 4,984 Danish-born HIV-infected individuals from the Danish HIV Cohort Study and a Danish born population-based age- and gender-matched comparison cohort of 19,936 individuals (study period: 1996–2009). Data on DM was obtained from the Danish National Hospital Registry and the Danish National Prescription Registry. Incidence rate ratios (IRR) and impact of risk factors including exposure to Highly Active Antiretroviral Therapy (HAART) and antiretroviral drugs were estimated by Poisson regression analyses. Results In the period 1996–1999 risk of DM was higher in HIV-infected individuals compared to the comparison cohort (adjusted IRR: 2.83; 95%CI: 1.57–5.09), both before (adjusted IRR: 2.40; 95%CI: 1.03–5.62) and after HAART initiation (adjusted IRR: 3.24; 95% CI: 1.42–7.39). In the period 1999–2010 the risk of DM in HIV-infected individuals did not differ from that of the comparison cohort (adjusted IRR: 0.90; 95% CI: 0.72–1.13), although the risk was decreased before HAART-initiation (adjusted IRR: 0.45; 95%CI: 0.21–0.96). Increasing age, BMI and the presence of lipoatrophy increased the risk of DM, as did exposure to indinavir, saquinavir, stavudine and didanosine. Conclusion Native HIV–infected individuals do not have an increased risk of developing DM compared to a native background population after year 1998. Some antiretroviral drugs, not used in modern antiretroviral treatment, seem to increase the risk of DM. PMID:22984529

  13. Prevalence of clinical signs of disease in Danish finisher pigs.

    PubMed

    Petersen, H H; Nielsen, E O; Hassing, A-G; Ersbøll, A K; Nielsen, J P

    2008-03-22

    Between December 1999 and February 2001, two visits, eight weeks apart, were made to 90 herds of Danish finisher pigs. The prevalence of clinical signs was recorded by three veterinary technicians from the Danish Bacon and Meat Council according to a standardised procedure; they had been trained and their observations were monitored and validated before and during the study. A total of 154,347 finisher pigs were examined and 22,136 clinical signs were recorded. Vices accounted for 43 per cent of the signs. The highest mean prevalence was observed for ear necrosis (4.44 per cent), followed by respiratory signs (2.17 per cent), lameness (1.92 per cent), other skin diseases (1.73 per cent), tail bites (1.26 per cent), umbilical hernia (0.78 per cent), flank bites (0.52 per cent), diarrhoea (0.27 per cent), respiratory distress (0.12 per cent), atrophic rhinitis (0.10 per cent), recumbency (0.09 per cent) and central nervous disease (0.05 per cent). The prevalence of atrophic rhinitis was higher in conventional herds than in specific pathogen-free herds. The prevalence of clinical signs of atrophic rhinitis was higher among finishers weighing 51 to 75 kg than among finishers weighing up to 50 kg, and the prevalence of respiratory signs was higher among finishers weighing 51 to 75 kg then among finishers weighing 76 to 100 kg. PMID:18359931

  14. Incidence of Otitis Media in a Contemporary Danish National Birth Cohort

    PubMed Central

    Todberg, Tanja; Koch, Anders; Andersson, Mikael; Olsen, Sjurdur F.; Lous, Jørgen; Homøe, Preben

    2014-01-01

    Objectives In recent years welfare in Denmark has increased which might be expected to reduce otitis media (OM) incidence. We examined the age-specific incidence of OM in a nation-wide cohort of children aged 0–7 years born in 1996–2003 (Danish National Birth Cohort, DNBC). Only selection was ability to understand and speak Danish. Methods Information of OM and ventilation tubes (VT) was collected through three maternal interviews at 6-month, 18-month and 7-years of age and based on this age-specific and cumulative incidence of OM was calculated. As different numbers of the total population answered the different interviews, the calculations are done with different denominators. The information in DNBC was validated against two population based registries containing information of VT insertions. Results Cumulative incidence of OM at 7 years was 60.6% (31,982/52,755). For children with OM, 16.2% (7143/44194) had their first OM episodes between 0–6 months of age, 44.3% (19579/44194) between 7–18 months, and 39.5% (17472/44194) between 19 months and 7 years. Four or more OM episodes before 7 years were reported by 39.5% (12620/31982) and by 64.0% (2482/3881) of those who had their OM debut between 0–6 months; by 48.2% (4998/10378) with debut between 7–18 months; and by 28.7% (4996/17344) with debut between 19 months and 7 years. These figures are essentially unchanged from earlier figures from Denmark. VT insertion at least once was reported by 26,1% in the 7-year interview. Assuming recordings in the Danish National Patient Registry to be gold standard, maternal self-reportings in DNBC of insertion of VT showed high sensitivity (96.4%), specificity (98.2%), and positive (94.8%) and negative predictive values (98.8%). Conclusion OM affects nearly 2/3 of preschool children in Denmark despite reduction in known OM risk factors. PMID:25545891

  15. National Cohort Study of Suicidality and Violent Criminality among Danish Immigrants

    PubMed Central

    Webb, Roger T.; Antonsen, Sussie; Mok, Pearl L. H.; Agerbo, Esben; Pedersen, Carsten B.

    2015-01-01

    Background Immigrant populations in western societies have grown in their size and diversity yet evidence is incomplete for their risks of suicidality and criminal violence. We examined these correlated harmful behaviours in a national cohort. Aims (i) Compare absolute risk between first and second generation immigrants, foreign-born adoptees and native Danes by plotting cumulative incidence curves to onset of early middle age; (ii) estimate sex-specific relative risks for these immigrant type subgroups vs. native Danes; (iii) examine effect modification by higher vs. lower socio-economic status. Methods In a cohort of over two million persons, attempted suicides and violent crimes were investigated using data from multiple interlinked registers. We plotted sex-specific cumulative incidence curves and estimated incidence rate ratios. Results In the whole study cohort, 1414 people died by suicide, 46,943 attempted suicide, and 51,344 were convicted of committing a violent crime. Among all immigrant subgroups combined, compared with native Danes, relative risk of attempted suicide was greater in female immigrants (incidence rate ratio, 1.59; 95% confidence interval: CI 1.54-1.64) than in male immigrants (1.26; CI 1.20-1.32), and vice versa for relative risk of violent offending in male immigrants (2.36; CI 2.31-2.42) than in female immigrants (1.74; CI 1.62-1.87). Risk for both adverse outcomes was significantly elevated in virtually every gender-specific immigrant type subgroup examined. Violent crime risk was markedly raised in first generation immigrant males and in the Danish born male children of two immigrant parents. However, male immigrants of lower social status had lower risk of attempted suicide than their native Danish peers. Conclusion Young immigrants of both first and second generation status face serious challenges and vulnerabilities that western societies need to urgently address. Relative risk patterns for these adverse outcomes vary greatly

  16. Association between sexually transmitted disease and church membership. A retrospective cohort study of two Danish religious minorities

    PubMed Central

    Kørup, Alex Kappel; Thygesen, Lau Caspar; Christensen, René dePont; Johansen, Christoffer; Søndergaard, Jens; Hvidt, Niels Christian

    2016-01-01

    Objectives Studies comprising Danish Seventh-day Adventists (SDAs) and Danish Baptists found that members have a lower risk of chronic diseases including cancer. Explanations have pointed to differences in lifestyle, but detailed aetiology has only been sparsely examined. Our objective was to investigate the incidence of sexually transmitted diseases (STDs) among Danish SDAs and Baptists as a proxy for cancers related to sexual behaviour. Methods We followed the Danish Cohort of Religious Societies from 1977 to 2009, and linked it with national registers of all inpatient and outpatient care contacts using the National Patient Register. We compared the incidence of syphilis, gonorrhoea and chlamydia among members of the cohort with the general population. Results The cohort comprised 3119 SDA females, 1856 SDA males, 2056 Baptist females and 1467 Baptist males. For the entire cohort, we expected a total of 32.4 events of STD, and observed only 9. Female SDAs and Baptists aged 20–39 years had significant lower incidence of chlamydia (both p<0.001). Male SDAs and Baptists aged 20–39 years also had significant lower incidence of chlamydia (p<0.01 and p<0.05, respectively). No SDA members were diagnosed with gonorrhoea, when 3.4 events were expected, which, according to Hanley's ‘rule of three’, is a significant difference. No SDA or Baptist was diagnosed with syphilis. Conclusions The cohort shows significant lower incidence of STD, most likely including human papillomavirus, which may partly explain the lower incidence of cancers of the cervix, rectum, anus, head and neck. PMID:27016243

  17. Lung cancer in HIV patients and their parents: A Danish cohort study

    PubMed Central

    2011-01-01

    Background HIV patients are known to be at increased risk of lung cancer but the risk factors behind this are unclear. Methods We estimated the cumulative incidence and relative risk of lung cancer in 1) a population of all Danish HIV patients identified from the Danish HIV Cohort Study (n = 5,053) and a cohort of population controls matched on age and gender (n = 50,530) (study period; 1995 - 2009) and 2) their parents (study period; 1969 - 2009). Mortality and relative risk of death after a diagnosis of lung cancer was estimated in both populations. Results 29 (0.6%) HIV patients vs. 183 (0.4%) population controls were diagnosed with lung cancer in the observation period. HIV patients had an increased risk of lung cancer (adjusted incidence rate ratio (IRR); 2.38 (95% CI; 1.61 - 3.53)). The IRR was considerably increased in HIV patients who were smokers or former smokers (adjusted IRR; 4.06 (95% CI; 2.66 - 6.21)), male HIV patients with heterosexual route of infection (adjusted IRR; 4.19 (2.20 - 7.96)) and HIV patients with immunosuppression (adjusted IRR; 3.25 (2.01 - 5.24)). Both fathers and mothers of HIV patients had an increased risk of lung cancer (adjusted IRR for fathers; 1.31 (95% CI: 1.09 - 1.58), adjusted IRR for mothers 1.35 (95% CI: 1.07 - 1.70)). Mortality after lung cancer diagnose was increased in HIV patients (adjusted mortality rate ratio 2.33 (95%CI; 1.51 - 3.61), but not in the parents. All HIV patients diagnosed with lung cancer were smokers or former smokers. Conclusion The risk was especially increased in HIV patients who were smokers or former smokers, heterosexually infected men or immunosuppressed. HIV appears to be a marker of behavioural or family related risk factors that affect the incidence of lung cancer in HIV patients. PMID:21702995

  18. Residential Radon Exposure and Skin Cancer Incidence in a Prospective Danish Cohort

    PubMed Central

    Bräuner, Elvira Vaclavik; Loft, Steffen; Sørensen, Mette; Jensen, Allan; Andersen, Claus Erik; Ulbak, Kaare; Hertel, Ole; Pedersen, Camilla; Tjønneland, Anne; Krüger Kjær, Susanne; Raaschou-Nielsen, Ole

    2015-01-01

    Background Although exposure to UV radiation is the major risk factor for skin cancer, theoretical models suggest that radon exposure can contribute to risk, and this is supported by ecological studies. We sought to confirm or refute an association between long-term exposure to residential radon and the risk for malignant melanoma (MM) and non-melanoma skin cancer (NMSC) using a prospective cohort design and long-term residential radon exposure. Methods During 1993–1997, we recruited 57,053 Danish persons and collected baseline information. We traced and geocoded all residential addresses of the cohort members and calculated radon concentrations at each address lived in from 1 January 1971 until censor date. Cox proportional hazards models were used to estimate incidence rate-ratios (IRR) and confidence intervals (CI) for the risk associated with radon exposure for NMSC and MM, and effect modification was assessed. Results Over a mean follow-up of 13.6 years of 51,445 subjects, there were 3,243 cases of basal cell carcinoma (BCC), 317 cases of squamous cell carcinoma (SCC) and 329 cases of MM. The adjusted IRRs per 100 Bq/m3 increase in residential radon levels for BCC, SCC and MM were 1.14 (95% CI: 1.03, 1.27), 0.90 (95% CI: 0.70, 1.37) and 1.08 (95% CI: 0.77, 1.50), respectively. The association between radon exposure and BCC was stronger among those with higher socio-economic status and those living in apartments at enrollment. Conclusion and Impact Long-term residential radon exposure may contribute to development of basal cell carcinoma of the skin. We cannot exclude confounding from sunlight and cannot conclude on causality, as the relationship was stronger amongst persons living in apartments and non-existent amongst those living in single detached homes. PMID:26274607

  19. Distribution and predictors of exercise habits among pregnant women in the Danish National Birth Cohort.

    PubMed

    Juhl, M; Madsen, M; Andersen, A-M N; Andersen, P K; Olsen, J

    2012-02-01

    Physical activity is recommended during pregnancy, although strong evidence on reproductive health is lacking. We present exercise habits and predictors of exercise during pregnancy. From the Danish National Birth Cohort (1996-2002), 88,200 singleton pregnancies were analyzed in logistic regression. About one-third of the women exercised in early/mid pregnancy and slightly less in late pregnancy. Bicycling, swimming, and low-impact activities were most common. Exercising more than three times per week was strongly correlated with older age, being a student or out of work, eating disorders, moderate alcohol consumption, and a healthy diet. Multiparity, a normal or less good self-rated health, smoking, and a less health conscious diet were the strongest predictors of not doing exercise. Women of 25 years or older, with metabolic or psychiatric disorders, or who had received subfecundity treatment were more likely to increase their activity level substantially from early to late pregnancy than comparison groups. In conclusion, exercising during pregnancy correlated with a number of maternal characteristics. The findings may be used to identify pregnant women not likely to exercise, to target activities that may fit their needs, and, for research purposes, to identify adjustment variables or guide sensitivity analyses when data on confounders are lacking. PMID:20500556

  20. Parental celiac disease and risk of asthma in offspring: a Danish nationwide cohort study

    PubMed Central

    Andersen, Ane Birgitte Telén; Erichsen, Rune; Kappelman, Michael David; Frøslev, Trine; Ehrenstein, Vera

    2015-01-01

    Objective The incidences of celiac disease (CD) and asthma are increasing and the two conditions are associated in individuals. Risk of asthma may be passed on to the next generation through shared risk factors. We examined whether parental CD is associated with risk of asthma in offspring. Methods We conducted a population-based Danish nationwide cohort study, using medical databases, covering the period 1 January 1979 to 31 December 2009. For each child with a parental history of CD, we randomly sampled 100 children without this history from the children born in the same calendar year. We used Cox proportional-hazards regression to estimate incidence rate ratios for asthma, adjusting for measured covariates. Results We identified 1,107 children with a parental history of CD and 110,700 children without this parental history. During up to 32 years of follow-up, 6,125 children received a hospital diagnosis of asthma. The adjusted incidence rate ratio for asthma associated with a parental history of CD was 1.09 (95% confidence interval: 0.86–1.39) and was similar for maternal and paternal CD. Inclusion of asthma-medication in the definition of asthma did not substantially change the results. Conclusion There was no convincing evidence of an increased risk of asthma among offspring of parents with CD. PMID:25565892

  1. Placental Weight and Male Genital Anomalies: A Nationwide Danish Cohort Study.

    PubMed

    Arendt, Linn Håkonsen; Ramlau-Hansen, Cecilia Høst; Wilcox, Allen J; Henriksen, Tine Brink; Olsen, Jørn; Lindhard, Morten Søndergaard

    2016-06-15

    The most consistently reported risk indicators for the male genital anomalies cryptorchidism and hypospadias are prematurity and low birth weight. Placental dysfunction has been hypothesized as a possible underlying cause, and an association between placental weight at birth and hypospadias has been indicated. In a population-based cohort of 388,422 Danish singleton boys born alive (1997-2008), we studied the association between placental weight and cryptorchidism and hypospadias. Missing data were handled with multiple imputation, and we estimated hazard ratios by means of Cox regression models. During follow-up, 1,713 boys were diagnosed with hypospadias and 6,878 with cryptorchidism (3,624 underwent corrective surgery). We observed an association between low placental weight and risk of both genital anomalies. Boys with a placental weight in the lowest decile (<10%) had higher risks of both cryptorchidism (hazard ratio = 1.52, 95% confidence interval: 1.31, 1.76) and hypospadias (hazard ratio = 1.97, 95% confidence interval: 1.59, 2.45) than boys in the reference decile (50.0-59.9%). In conclusion, we found higher risks of both genital malformations in boys born with a low placental weight. The relationship seemed stronger for hypospadias than for cryptorchidism. Taken together, our data support a role for placental dysfunction in the etiology of these anomalies. PMID:27257113

  2. Pre-gravid oral contraceptive use and time to pregnancy: a Danish prospective cohort study

    PubMed Central

    Mikkelsen, Ellen M.; Riis, Anders H.; Wise, Lauren A.; Hatch, Elizabeth E.; Rothman, Kenneth J.; Toft Sørensen, Henrik

    2013-01-01

    STUDY QUESTION Is there an association between oral contraceptive (OC) use (age at the start of use, duration of use, ethinylestradiol dose and generation) and time to pregnancy (TTP)? SUMMARY ANSWER Although OC use was associated with a transient delay in the return of fertility, we found no evidence that long-term OC use deleteriously affects fecundability. WHAT IS KNOWN ALREADY Studies using retrospective data on TTP have reported a short-term delay in the return of fertility after OC use. However, little is known about the long-term OC use and TTP. STUDY DESIGN, SIZE, DURATION Data were derived from ‘Snart Gravid.dk’, a prospective cohort study that enrolled participants from 1 June 2007 to 31 May 2010. The final study population consisted of 3727 women. PARTICIPANTS, SETTING, METHODS Eligible women were Danish pregnancy planners, aged 18–40 years, who completed a baseline questionnaire and bimonthly follow-up questionnaires until conception or for 12 months, whichever came first. Cohort retention was 80%. We used proportional probability regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), with adjustment for potential confounders. MAIN RESULTS AND ROLE OF CHANCE Compared with barrier methods, the use of OCs as the last contraception method before attempting to conceive was associated with a short-term delay in return of fertility (FR = 0.87, 95% CI: 0.79–0.96). Longer term OC use was associated with higher fecundability: compared with OC use for less than 2 years; FRs were 0.98 (95% CI: 0.83–1.15) for 2–3 years, 1.16 (95% CI: 0.98–1.37) for 4–5 years, 1.10 (95% CI: 0.93–1.29) for 6–7 years, 1.17 (95% CI: 0.99–1.38) for 8–9 years, 1.23 (95% CI: 1.04–1.46) for 10–11 years and 1.28 (95% CI: 1.07–1.53) for ≥12 years of OC use. LIMITATIONS, REASONS FOR CAUTION Because this was a non-experimental study, where study volunteers provided information about their history of contraceptive use at

  3. Traffic air pollution and mortality from cardiovascular disease and all causes: a Danish cohort study

    PubMed Central

    2012-01-01

    Background Traffic air pollution has been linked to cardiovascular mortality, which might be due to co-exposure to road traffic noise. Further, personal and lifestyle characteristics might modify any association. Methods We followed up 52 061 participants in a Danish cohort for mortality in the nationwide Register of Causes of Death, from enrollment in 1993–1997 through 2009, and traced their residential addresses from 1971 onwards in the Central Population Registry. We used dispersion-modelled concentration of nitrogen dioxide (NO2) since 1971 as indicator of traffic air pollution and used Cox regression models to estimate mortality rate ratios (MRRs) with adjustment for potential confounders. Results Mean levels of NO2 at the residence since 1971 were significantly associated with mortality from cardiovascular disease (MRR, 1.26; 95% confidence interval [CI], 1.06–1.51, per doubling of NO2 concentration) and all causes (MRR, 1.13; 95% CI, 1.04–1.23, per doubling of NO2 concentration) after adjustment for potential confounders. For participants who ate < 200 g of fruit and vegetables per day, the MRR was 1.45 (95% CI, 1.13–1.87) for mortality from cardiovascular disease and 1.25 (95% CI, 1.11–1.42) for mortality from all causes. Conclusions Traffic air pollution is associated with mortality from cardiovascular diseases and all causes, after adjustment for traffic noise. The association was strongest for people with a low fruit and vegetable intake. PMID:22950554

  4. Early child care and obesity at 12 months of age in the Danish National Birth Cohort

    PubMed Central

    Neelon, Sara E Benjamin; Andersen, Camilla Schou; Morgen, Camilla Schmidt; Kamper-Jørgensen, Mads; Oken, Emily; Gillman, Matthew W; Sørensen, Thorkild IA

    2014-01-01

    Background/Objectives Evidence suggests that the child care environment may be more obesogenic than the family home, and previous studies have found that child care use may be associated with obesity in children. Few studies, however, have focused on child care during infancy, which may be an especially vulnerable period. This study examined child care use in infancy and weight status at 12 months of age in a country where paid maternity leave is common and early child care is not as prevalent as in other developed countries. Subjects/Methods We studied 27821 children born to mothers participating in the Danish National Birth Cohort (DNBC), a longitudinal study of pregnant women enrolled between 1997 and 2002, who were also included in the Childcare Database, a national record of child care use in Denmark. The exposure was days in child care from birth to 12 months. The outcomes were sex-specific body mass index (BMI) z-score and overweight/obesity (BMI ≥85th percentile based on the World Health Organization classification) at 12 months. We conducted multivariable linear and logistic regression analyses examining child care use and weight outcomes. Results A total of 17721 (63.7%) children attended child care during their first year of life. After adjustment for potential confounders, a 30-day increment of child care was associated with a modestly higher BMI z-score at 12 months (0.03 units; 95% CI: 0.01, 0.05; p=0.003). Similarly, child care use was associated with increased odds of being overweight/obese at 12 months of age (OR 1.05; 95% CI: 1.01, 1.10; p=0.047). Conclusions Child care in the first year of life was associated with slightly higher weight at 12 months, suggesting that child care settings may be important targets for obesity prevention in infancy. PMID:25233894

  5. Risk of Multiple Sclerosis in Patients with Psoriasis: A Danish Nationwide Cohort Study.

    PubMed

    Egeberg, Alexander; Mallbris, Lotus; Gislason, Gunnar Hilmar; Skov, Lone; Hansen, Peter Riis

    2016-01-01

    Psoriasis and multiple sclerosis (MS) are inflammatory disorders with similarities in genetic risk variants and inflammatory pathways. Limited evidence is available on the relationship between the two diseases. We therefore investigated the risk of incident (new-onset) MS in patients with mild and severe psoriasis, respectively. All Danish citizens aged ≥ 18 years from 1 January 1997 to 31 December 2011 were identified by linkage of nationwide registries at the individual level. We estimated incidence rate ratios (IRRs) adjusted for age, gender, socioeconomic status, smoking, medication, comorbidity, and UV phototherapy by Poisson regression. There were 58,628 and 9,952 cases of mild and severe psoriasis, respectively, and 9,713 cases of MS. Incidence rates of MS per 10,000 person-years for the reference population, mild psoriasis, and severe psoriasis were 1.78, 3.22, and 4.55, respectively. Adjusted IRRs of MS were 1.84 (95% confidence interval [CI], 1.46-2.30) and 2.61 (95% CI, 1.44-4.74) in mild and severe psoriasis, respectively. Similar results were observed when adjustment for family history of MS was included in the analyses. Psoriasis may confer a disease severity-dependent risk of MS. Further studies are warranted to establish the mechanisms underlying this relationship and its potential clinical consequences. PMID:26763428

  6. Prematurity and Prescription Asthma Medication from Childhood to Young Adulthood: A Danish National Cohort Study

    PubMed Central

    Damgaard, Anne Louise; Hansen, Bo Mølholm; Mathiasen, René; Buchvald, Frederik; Lange, Theis; Greisen, Gorm

    2015-01-01

    Introduction Preterm birth is associated with increased risk of asthma-like symptoms and purchase of prescription asthma medication in childhood. We investigated whether this association persists into adulthood and whether it is affected by accounting for neonatal respiratory morbidity (acute respiratory disease and bronchopulmonary dysplasia). Methods A national cohort of all infants born in Denmark in the period 1980–2009 was included in this register study. Data on purchase of asthma medication (combination of inhaled β-2 agonists and other drugs for obstructive airway disease) in 2010–2011 were obtained from the Danish National Prescription Registry. Associations between gestational age (GA), neonatal respiratory morbidity and a cross-sectional evaluation of asthma medication purchase were explored by multivariate logistic regressions. Results A full dataset was obtained on 1,790,241 individuals, 84.6% of all infants born in the period. Odds-ratios (95% CI) for the association between GA and purchase of asthma medication during infancy were: 3.86 (2.46–6.04) in GA 23–27 weeks, 2.37 (1.84–3.04) in GA 28–31 weeks and 1.59 (1.43–1.77) in GA 32–36 weeks compared to term infants with GA 37–42 weeks. Associations weakened in older age groups and became insignificant in young adults born extremely and very preterm with odds-ratios: 1.41 (0.63–3.19) and 1.15 (0.83–1.60) in GA 23–27 and 28–31 respectively. When adjusting for neonatal respiratory morbidity, the associations weakened but persisted both in childhood and adolescence. Conclusion There was a strong dose-response association between gestational age and the purchase of prescription asthma medication in infancy and childhood. This association weakened during adolescence and was mostly non-significant in young adulthood. The increased risk of prescription asthma medication purchase in ex-preterm children could only partly be explained by neonatal respiratory morbidity. PMID:25651521

  7. Broad-Spectrum Antibiotic Treatment and Subsequent Childhood Type 1 Diabetes: A Nationwide Danish Cohort Study

    PubMed Central

    Bergholt, Thomas; Bouaziz, Olivier; Arpi, Magnus; Eriksson, Frank; Rasmussen, Steen; Keiding, Niels; Løkkegaard, Ellen C.

    2016-01-01

    Background Studies link antibiotic treatment and delivery by cesarean section with increased risk of chronic diseases through changes of the gut-microbiota. We aimed to evaluate the association of broad-spectrum antibiotic treatment during the first two years of life with subsequent onset of childhood type 1 diabetes and the potential effect-modification by mode of delivery. Materials and Methods A Danish nationwide cohort study including all singletons born during 1997–2010. End of follow-up by December 2012. Four national registers provided information on antibiotic redemptions, outcome and confounders. Redemptions of antibiotic prescriptions during the first two years of life was classified into narrow-spectrum or broad-spectrum antibiotics. Children were followed from age two to fourteen, both inclusive. The risk of type 1 diabetes with onset before the age of 15 years was assessed by Cox regression. A total of 858,201 singletons contributed 5,906,069 person-years, during which 1,503 children developed type 1 diabetes. Results Redemption of broad-spectrum antibiotics during the first two years of life was associated with an increased rate of type 1 diabetes during the following 13 years of life (HR 1.13; 95% CI 1.02 to 1.25), however, the rate was modified by mode of delivery. Broad-spectrum antibiotics were associated with an increased rate of type 1 diabetes in children delivered by either intrapartum cesarean section (HR 1.70; 95% CI 1.15 to 2.51) or prelabor cesarean section (HR 1.63; 95% CI 1.11 to 2.39), but not in vaginally delivered children. Number needed to harm was 433 and 562, respectively. The association with broad-spectrum antibiotics was not modified by parity, genetic predisposition or maternal redemption of antibiotics during pregnancy or lactation. Conclusions Redemption of broad-spectrum antibiotics during infancy is associated with an increased risk of childhood type 1 diabetes in children delivered by cesarean section. PMID:27560963

  8. Maternal Use of Antibiotics and the Risk of Childhood Febrile Seizures: A Danish Population-Based Cohort

    PubMed Central

    Miller, Jessica E.; Pedersen, Lars Henning; Vestergaard, Mogens; Olsen, Jørn

    2013-01-01

    Objective In a large population-based cohort in Denmark to examine if maternal use of antibiotics during pregnancy, as a marker of infection, increases the risk of febrile seizures in childhood in a large population-based cohort in Denmark. Methods All live-born singletons born in Denmark between January 1, 1996 and September 25, 2004 and who were alive on the 90th day of life were identified from the Danish National Birth Registry. Diagnoses of febrile seizures were obtained from the Danish National Hospital Register and maternal use of antibiotics was obtained from the National Register of Medicinal Product Statistics. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox proportional hazard regression models. Results We followed 551,518 singletons for up to 5 years and identified a total of 21,779 children with a diagnosis of febrile seizures. Slightly increased hazard ratios were observed among most exposure groups when compared to the unexposed group, ex. HR 1.08 95% CI: 1.05–1.11 for use of any systemic antibiotic during pregnancy. Conclusion We found weak associations between the use of pharmacologically different antibiotics during pregnancy and febrile seizures in early childhood which may indicate that some infections, or causes or effects of infections, during pregnancy could affect the fetal brain and induce susceptibility to febrile seizures. PMID:23613800

  9. The 16-year incidence, progression and regression of diabetic retinopathy in a young population-based Danish cohort with type 1 diabetes mellitus: The Danish cohort of pediatric diabetes 1987 (DCPD1987).

    PubMed

    Broe, Rebecca; Rasmussen, Malin Lundberg; Frydkjaer-Olsen, Ulrik; Olsen, Birthe Susanne; Mortensen, Henrik Bindesboel; Peto, Tunde; Grauslund, Jakob

    2014-01-01

    The aim was to investigate the long-term incidence of proliferative diabetic retinopathy (PDR), and progression and regression of diabetic retinopathy (DR) and associated risk factors in young Danish patients with Type 1 diabetes mellitus. In 1987-89, a pediatric cohort involving approximately 75 % of all children with Type 1 diabetes in Denmark <19 years of age was identified (n = 720). In 1995, 339 (47.1 %) were re-studied with retinopathy graded and all relevant diabetic parameters assessed. Of those, 185 (54.6 %) were evaluated again in 2011 for the same clinical parameters. All retinal images were graded using modified early treatment of DR study for 1995 and 2011. In 1995, mean age was 21.0 years and mean diabetes duration 13.5 years. The 16-year incidence of proliferative retinopathy, 2-step progression and 2-step regression of DR was 31.0, 64.4 and 0.0 %, respectively, while the incidence of DR was 95.1 %. In a multivariate logistic regression model, progression to PDR was significantly associated with 1995 HbA1c (OR 2.61 per 1 % increase, 95 % CI 1.85-3.68) and 1995 diastolic blood pressure (OR 1.79 per 10 mmHg increase, 95 % CI 1.04-3.07). Two-step progression of DR was associated with male gender (OR 2.37 vs. female, 95 % CI 1.07-5.27), 1995 HbA1c (OR 3.02 per 1 % increase, 95 % CI 2.04-4.48) and 1995 vibration perception threshold (OR 1.19 per 1 Volt increase, 95 % CI 1.02-1.40). In conclusion, one in three progressed to PDR and two in three had 2-step progression despite young age and increased awareness of the importance of metabolic control. After 30 years duration of diabetes, the presence of DR is almost universal. PMID:24193810

  10. A Danish Twin Study of Schizophrenia Liability: Investigation from Interviewed Twins for Genetic Links to Affective Psychoses and for Cross-Cohort Comparisons.

    PubMed

    Kläning, Ulla; Trumbetta, Susan L; Gottesman, Irving I; Skytthe, Axel; Kyvik, Kirsten O; Bertelsen, Aksel

    2016-03-01

    We studied schizophrenia liability in a Danish population-based sample of 44 twin pairs (13 MZ, 31 DZ, SS plus OS) in order to replicate previous twin study findings using contemporary diagnostic criteria, to examine genetic liability shared between schizophrenia and other disorders, and to explore whether variance in schizophrenia liability attributable to environmental factors may have decreased with successive cohorts exposed to improvements in public health. ICD-10 diagnoses were determined by clinical interview. Although the best-fitting, most parsimonious biometric model of schizophrenia liability specified variance attributable to additive genetic and non-shared environmental factors, this model did not differ significantly from a model that also included non-additive genetic factors, consistent with recent interview-based twin studies. Schizophrenia showed strong genetic links to other psychotic disorders but much less so for the broader category of psychiatric disorders in general. We also observed a marginally significant decline in schizophrenia variance attributable to environmental factors over successive Western European cohorts, consistent perhaps with improvements in diagnosis and in prenatal and perinatal care and with a secular decline in the prevalence of schizophrenia in that region. PMID:26538243

  11. Maternal dietary patterns during pregnancy in relation to offspring forearm fractures: prospective study from the Danish National Birth Cohort.

    PubMed

    Petersen, Sesilje B; Rasmussen, Morten A; Olsen, Sjurdur F; Vestergaard, Peter; Mølgaard, Christian; Halldorsson, Thorhallur I; Strøm, Marin

    2015-04-01

    Limited evidence exists for an association between maternal diet during pregnancy and offspring bone health. In a prospective study, we examined the association between dietary patterns in mid-pregnancy and offspring forearm fractures. In total, 101,042 pregnancies were recruited to the Danish National Birth Cohort (DNBC) during 1996-2002. Maternal diet was collected by a food frequency questionnaire. Associations were analyzed between seven dietary patterns extracted by principal component analysis and offspring first occurrence of any forearm fracture diagnosis, extracted from the Danish National Patient Register, between time of birth and end of follow-up (< 16 year) (n = 53,922). In multivariable Cox regression models, offspring of mothers in the fourth vs. first quintile of the Western pattern had a significant increased risk (Hazard ratio, 95% confidence interval: 1.11, 1.01-1.23) of fractures, and there was a borderline significant positive trend (p = 0.06). The other dietary patterns showed no associations and neither did supplementary analyses of macro- and micronutrients or single food groups, except for the intake of artificially sweetened soft drinks, which was positively associated with offspring forearm fractures (p = 0.02). In the large prospective DNBC high mid-pregnancy consumption of Western diet and artificially sweetened soft drinks, respectively, indicated positive associations with offspring forearm fractures, which provides interesting hypotheses for future research. PMID:25849947

  12. Maternal Dietary Patterns during Pregnancy in Relation to Offspring Forearm Fractures: Prospective Study from the Danish National Birth Cohort

    PubMed Central

    Petersen, Sesilje B.; Rasmussen, Morten A.; Olsen, Sjurdur F.; Vestergaard, Peter; Mølgaard, Christian; Halldorsson, Thorhallur I.; Strøm, Marin

    2015-01-01

    Limited evidence exists for an association between maternal diet during pregnancy and offspring bone health. In a prospective study, we examined the association between dietary patterns in mid-pregnancy and offspring forearm fractures. In total, 101,042 pregnancies were recruited to the Danish National Birth Cohort (DNBC) during 1996–2002. Maternal diet was collected by a food frequency questionnaire. Associations were analyzed between seven dietary patterns extracted by principal component analysis and offspring first occurrence of any forearm fracture diagnosis, extracted from the Danish National Patient Register, between time of birth and end of follow-up (<16 year) (n = 53,922). In multivariable Cox regression models, offspring of mothers in the fourth vs. first quintile of the Western pattern had a significant increased risk (Hazard ratio, 95% confidence interval: 1.11, 1.01–1.23) of fractures, and there was a borderline significant positive trend (p = 0.06). The other dietary patterns showed no associations and neither did supplementary analyses of macro- and micronutrients or single food groups, except for the intake of artificially sweetened soft drinks, which was positively associated with offspring forearm fractures (p = 0.02). In the large prospective DNBC high mid-pregnancy consumption of Western diet and artificially sweetened soft drinks, respectively, indicated positive associations with offspring forearm fractures, which provides interesting hypotheses for future research. PMID:25849947

  13. Prenatal Exposure to Phthalates and Anogenital Distance in Male Infants from a Low-Exposed Danish Cohort (2010–2012)

    PubMed Central

    Jensen, Tina Kold; Frederiksen, Hanne; Kyhl, Henriette Boye; Lassen, Tina Harmer; Swan, Shanna H.; Bornehag, Carl-Gustaf; Skakkebaek, Niels E.; Main, Katharina M.; Lind, Dorte Vesterholm; Husby, Steffen; Andersson, Anna-Maria

    2015-01-01

    Background: Phthalates comprise a large class of chemicals used in a variety of consumer products. Several have anti-androgenic properties, and in rodents prenatal exposure has been associated with reduced anogenital distance (AGD)—the distance from the anus to the genitals in male offspring. Few human studies have been conducted, but associations between the anti-androgenic phthalates and male AGD have been reported. Objective: We aimed to study the association between phthalate exposure in late pregnancy in Danish women pregnant in 2010–2012 and AGD in their male infants at 3 months of age (n = 273). Methods: In the Odense child cohort study, urinary concentrations of 12 phthalate metabolites of diethyl, di-n-butyl, diisobutyl, di(2-ethylhexyl), butylbenzyl, and diisononyl phthalate (DEP, DnBP, DiBP, DEHP, BBzP, and DiNP, respectively) were measured among 245 mothers of boys at approximately gestational week 28 (range, 20.4–30.4) and adjusted for osmolality. AGD, penile width, and weight were measured 3 months after the expected date of birth. Associations between prenatal phthalate and AGD and penile width were estimated using multivariable linear regression adjusting for age and weight-for-age standard deviation score. Results: Phthalate levels were lower in this population than in a recent Swedish study in which phthalates were measured in the first trimester. No consistent associations were seen between any prenatal phthalate and AGD or penile width. Most associations were negative for exposures above the first quartile, and for ln-transformed exposures modeled as continuous variables, but there were no consistent dose–response patterns, and associations were not statistically significant (p > 0.05). Conclusion: We found no significant trends towards shorter AGD in boys with higher phthalates exposures in this low exposed Danish population. Citation: Jensen TK, Frederiksen H, Kyhl HB, Lassen TH, Swan SH, Bornehag CG, Skakkebaek NE, Main KM, Lind DV

  14. SpineData – a Danish clinical registry of people with chronic back pain

    PubMed Central

    Kent, Peter; Kongsted, Alice; Jensen, Tue Secher; Albert, Hanne B; Schiøttz-Christensen, Berit; Manniche, Claus

    2015-01-01

    Background Large-scale clinical registries are increasingly recognized as important resources for quality assurance and research to inform clinical decision-making and health policy. We established a clinical registry (SpineData) in a conservative care setting where more than 10,000 new cases of spinal pain are assessed each year. This paper describes the SpineData registry, summarizes the characteristics of its clinical population and data, and signals the availability of these data as a resource for collaborative research projects. Methods The SpineData registry is an Internet-based system that captures patient data electronically at the point of clinical contact. The setting is the government-funded Medical Department of the Spine Centre of Southern Denmark, Hospital Lillebaelt, where patients receive a multidisciplinary assessment of their chronic spinal pain. Results Started in 2011, the database by early 2015 contained information on more than 36,300 baseline episodes of patient care, plus the available 6-month and 12-month follow-up data for these episodes. The baseline questionnaire completion rate has been 93%; 79% of people were presenting with low back pain as their main complaint, 6% with mid-back pain, and 15% with neck pain. Collectively, across the body regions and measurement time points, there are approximately 1,980 patient-related variables in the database across a broad range of biopsychosocial factors. To date, 36 research projects have used data from the SpineData registry, including collaborations with researchers from Denmark, Australia, the United Kingdom, and Brazil. Conclusion We described the aims, development, structure, and content of the SpineData registry, and what is known about any attrition bias and cluster effects in the data. For epidemiology research, these data can be linked, at an individual patient level, to the Danish population-based registries and the national spinal surgery registry. SpineData also has potential for the

  15. Plasma enterolactone and incidence of endometrial cancer in a case-cohort study of Danish women.

    PubMed

    Aarestrup, Julie; Kyrø, Cecilie; Knudsen, Knud E B; Weiderpass, Elisabete; Christensen, Jane; Kristensen, Mette; Würtz, Anne M L; Johnsen, Nina F; Overvad, Kim; Tjønneland, Anne; Olsen, Anja

    2013-06-28

    The phyto-oestrogen enterolactone has been hypothesised to protect against hormone-dependent cancers, probably through its antioestrogenic potential. We investigated whether a higher level of plasma enterolactone was associated with a lower incidence of endometrial cancer in a case-cohort study in the ‘Diet, Cancer and Health’ cohort. The cohort study included 29 875 women aged 50–64 years enrolled between 1993 and 1997. Information on diet and lifestyle was provided by self-administrated questionnaires and blood was drawn from each participant. Time-resolved fluoroimmunoassay was used for biochemical determination of plasma enterolactone. A total of 173 cases and 149 randomly selected cohort members were included. We estimated incidence rate ratio (IRR) and 95% CI by a Cox proportional hazards model. A 20 nmol/l higher plasma concentration of enterolactone was associated with a non-significant lower risk of endometrial cancer (IRR 0.93, 95% CI 0.84, 1.04). When excluding women with low enterolactone concentrations (quartile 1) due to potential recent antibiotic use, the association became slightly stronger, but remained non-significant (IRR 0.90, 95% CI 0.79, 1.02). Menopausal status, hormone replacement therapy or BMI did not modify the association. In conclusion, we found some support for a possible inverse association between plasma enterolactone concentration and endometrial cancer incidence. PMID:23114205

  16. Hospital Contacts With Infection and Risk of Schizophrenia: A Population-Based Cohort Study With Linkage of Danish National Registers

    PubMed Central

    Nielsen, Philip R.; Benros, Michael. E.; Mortensen, Preben B.

    2014-01-01

    Infections and immune responses have been suggested to play an important role in the etiology of schizophrenia. Several studies have reported associations between maternal infections during pregnancy and the child’s risk of schizophrenia; however, infection during childhood and adolescence unrelated to maternal infection during pregnancy has not been studied to nearly the same extent and the results are far from conclusive. Data were drawn from 2 population-based registers, the Danish Psychiatric Central Register and the Danish National Hospital Register. We used a historical population-based cohort design and selected all individuals born in Denmark between 1981 and 1996 (n = 843 390). We identified all individuals with a first-time hospital contact with schizophrenia from 1991 through 2010. Out of the 3409 individuals diagnosed with schizophrenia, a total of 1549 individuals had had a hospital contact with infection before their schizophrenia diagnosis (45%). Our results indicate that individuals who have had a hospital contact with infection are more likely to develop schizophrenia (relative risk [RR] = 1.41; 95% CI: 1.32–1.51) than individuals who had not had such a hospital contact. Bacterial infection was the type of infection that was associated with the highest risk of schizophrenia (RR = 1.63; 95% CI: 1.47–1.82). Our study does not exclude that a certain type of infection may have a specific effect; yet, it does suggest that schizophrenia is associated with a wide range of infections. This association may be due to inflammatory responses affecting the brain or genetic and environmental risk factors aggregating in families. PMID:24379444

  17. Time trend in hospitalised chronic lower respiratory diseases among Danish building and construction workers, 1981–2009: a cohort study

    PubMed Central

    Tüchsen, Finn; Hannerz, Harald; Mølgaard, Ellen Fisher; Brauer, Charlotte; Kirkeskov, Lilli

    2012-01-01

    Objectives To show trends in age-standardised hospital admission ratios (SHR) for chronic lower respiratory diseases, estimated for Danish construction workers over three time periods (1981–1990, 1991–2000, 2001–2009). Design Within consecutive cohorts of all male building and construction workers in Denmark, selected occupations: bricklayers, carpenters, electricians, painters, plumbers and ‘other construction workers’ were followed up for hospitalisation due to chronic lower respiratory diseases. SHR was calculated for each occupation and time period. Time trend was calculated for construction workers at large using Poisson regression. Setting Denmark. Participants All gainfully employed male building and construction workers aged 20 or more. Primary and secondary outcome measures Age-standardised and gender-standardised hospitalisation ratios (SHR). Results The number of hospitalised construction workers at large was reduced from 1134 in the first 10-year period to 699 in the last 9-year period. Among all Danish males, it was, however, even more reduced as reflected in the expected number that was down from 1172 to 617. Hence, SHR increased from 97 during 1981–1990, 100 during 1991–2000 to 113 during 2001–2009. It means that SHR increased with an average rate of 0.76% per year (95% CI 0.28 to 1.24) during the study period. A low SHR=72 (95% CI 60 to 87) was found among carpenters in 1981–1990. From 2001 to 2009, high SHRs were found among painters (SHR=147; 95% CI 111 to 192) and plumbers (SHR=132; 95% CI 101 to 171). In general, the selected groups of construction workers had, however, a low or average SHR due to chronic lower respiratory diseases. Conclusions The number of hospitalised workers, suffering from chronic lower respiratory diseases, was reduced over time for construction workers, but for all economically active men, it was reduced even more. Therefore, SHR due to chronic lower respiratory diseases increased over time in the

  18. Initiation and persistence with dual antiplatelet therapy after acute myocardial infarction: a Danish nationwide population-based cohort study

    PubMed Central

    Green, Anders; Pottegård, Anton; Broe, Anne; Diness, Thomas Goldin; Emneus, Martha; Hasvold, Pål; Gislason, Gunnar H

    2016-01-01

    Objectives The study investigated dual antiplatelet therapy (DAPT) patterns over time and patient characteristics associated with the various treatments in a myocardial infarction (MI) population. Design A registry-based observational cohort study was performed using antecedent data. Setting This study linked morbidity, mortality and medication data from Danish national registries. Participants All 28 449 patients admitted to a Danish hospital with a first-time MI and alive at discharge from 2009 through 2012 were included. Primary and secondary outcome measures Primary outcome was initiation of DAPT and secondary outcomes comprised persistence in DAPT treatment and switches between DAPT treatments. Results The overall proportion of patients prescribed DAPT increased from 68% (CL 95% 67–69%) to 73% (CL 95% 72–74%) from 2009 to 2012. For treatment of patients with and without percutaneous coronary intervention (PCI), the corresponding numbers were from 87% (CL 95% 86–88%) to 91% (CL 95% 90–92%) and from 49% (CL 95% 47–50%) to 52% (CL 95% 51–54%), respectively. Non-PCI patients had a higher cardiovascular risk compared with PCI patients. Among PCI patients, age>75 years, atrial fibrillation, diabetes and peripheral arterial disease were associated with a higher risk of treatment breaks for DAPT. Among patients without PCI, ticagrelor treatment was associated with an increased risk of treatment breaks during the first 12 months compared with clopidogrel treatment. Conclusions From 2009 to 2012, there was an increase in the proportion of patients with MI receiving DAPT, and a longer duration of DAPT. Still, a large proportion of patients without PCI are discharged either without DAPT or with a short DAPT duration. These findings may indicate the need for more careful attention to DAPT for patients with MI not undergoing PCI in Denmark. PMID:27173812

  19. Academic performance of opposite-sex and same-sex twins in adolescence: A Danish national cohort study

    PubMed Central

    Petersen, Inge; Johnson, Wendy; Christensen, Kaare

    2015-01-01

    Testosterone is an important hormone in the sexual differentiation of the brain, contributing to differences in cognitive abilities between males and females. For instance, studies in clinical populations such as females with congenital adrenal hyperplasia (CAH) who are exposed to high levels of androgens in utero support arguments for prenatal testosterone effects on characteristics such as visuospatial cognition and behaviour. The comparison of opposite-sex (OS) and same-sex (SS) twin pairs can be used to help establish the role of prenatal testosterone. However, although some twin studies confirm a masculinizing effect of a male co-twin regarding for instance perception and cognition it remains unclear whether intra-uterine hormone transfer exists in humans. Our aim was to test the potential influences of testosterone on academic performance in OS twins. We compared ninth-grade test scores and teacher ratings of OS (n = 1812) and SS (n = 4054) twins as well as of twins and singletons (n = 13,900) in mathematics, physics/chemistry, Danish, and English. We found that males had significantly higher test scores in mathematics than females (.06–.15 SD), whereas females performed better in Danish (.33–.49 SD), English (.20 SD), and neatness (.45–.64 SD). However, we did not find that OS females performed better in mathematics than SS and singleton females, nor did they perform worse either in Danish or English. Scores for OS and SS males were similar in all topics. In conclusion, this study did not provide evidence for a masculinization of female twins with male co-twins with regard to academic performance in adolescence. PMID:25655669

  20. Academic performance of opposite-sex and same-sex twins in adolescence: A Danish national cohort study.

    PubMed

    Ahrenfeldt, Linda; Petersen, Inge; Johnson, Wendy; Christensen, Kaare

    2015-03-01

    Testosterone is an important hormone in the sexual differentiation of the brain, contributing to differences in cognitive abilities between males and females. For instance, studies in clinical populations such as females with congenital adrenal hyperplasia (CAH) who are exposed to high levels of androgens in utero support arguments for prenatal testosterone effects on characteristics such as visuospatial cognition and behaviour. The comparison of opposite-sex (OS) and same-sex (SS) twin pairs can be used to help establish the role of prenatal testosterone. However, although some twin studies confirm a masculinizing effect of a male co-twin regarding for instance perception and cognition it remains unclear whether intra-uterine hormone transfer exists in humans. Our aim was to test the potential influences of testosterone on academic performance in OS twins. We compared ninth-grade test scores and teacher ratings of OS (n=1812) and SS (n=4054) twins as well as of twins and singletons (n=13,900) in mathematics, physics/chemistry, Danish, and English. We found that males had significantly higher test scores in mathematics than females (.06-.15 SD), whereas females performed better in Danish (.33-.49 SD), English (.20 SD), and neatness (.45-.64 SD). However, we did not find that OS females performed better in mathematics than SS and singleton females, nor did they perform worse either in Danish or English. Scores for OS and SS males were similar in all topics. In conclusion, this study did not provide evidence for a masculinization of female twins with male co-twins with regard to academic performance in adolescence. PMID:25655669

  1. Whole grain, dietary fiber, and incidence of endometrial cancer in a Danish cohort study.

    PubMed

    Aarestrup, Julie; Kyrø, Cecilie; Christensen, Jane; Kristensen, Mette; Würtz, Anne Mette Lund; Johnsen, Nina Føns; Overvad, Kim; Tjønneland, Anne; Olsen, Anja

    2012-01-01

    Whole grains and dietary fiber might be inversely associated with endometrial cancer risk through their effects on sex hormone metabolism and body fat. We investigated whether a higher intake of whole grains and dietary fiber was associated with a lower incidence of endometrial cancer in the Diet, Cancer and Health cohort of 29,875 women aged 50-64 years at enrollment in 1993-1997. Information on diet and lifestyle was derived from self-administered questionnaires. The incidence rate ratios and 95% confidence intervals were estimated based on a Cox proportional hazards model. Of the 24,418 women included as cohort members, 217 had a diagnosis of endometrial cancer. No clear associations were found between intake of whole grains or dietary fiber and the incidence of endometrial cancer. PMID:23163844

  2. Occupational Lifting, Fetal Death and Preterm Birth: Findings from the Danish National Birth Cohort Using a Job Exposure Matrix

    PubMed Central

    Mocevic, Emina; Svendsen, Susanne Wulff; Jørgensen, Kristian Tore; Frost, Poul; Bonde, Jens Peter

    2014-01-01

    Objective We examined the association between occupational lifting during pregnancy and risk of fetal death and preterm birth using a job exposure matrix (JEM). Methods For 68,086 occupationally active women in the Danish National Birth Cohort, interview information on occupational lifting was collected around gestational week 16. We established a JEM based on information from women, who were still pregnant when interviewed. The JEM provided mean total loads lifted per day within homogeneous exposure groups as informed by job and industry codes. All women were assigned an exposure estimate from the JEM. We used Cox regression models with gestational age as underlying time variable and adjustment for covariates. Results We observed 2,717 fetal deaths and 3,128 preterm births within the study cohort. No exposure-response relation was observed for fetal death, but for women with a prior fetal death, we found a hazard ratio (HR) of 2.87 (95% CI 1.37, 6.01) for stillbirth (fetal death ≥22 completed gestational weeks) among those who lifted >200 kg/day. For preterm birth, we found an exposure-response relation for primigravid women, reaching a HR of 1.43 (95% CI 1.13, 1.80) for total loads >200 kg per day. These findings correspond to an excess fraction of 11% for stillbirth and 10% for preterm birth. Conclusion We found an increased risk of stillbirth among women with a prior fetal death, who lifted >200 kg/day, and an exposure-response relationship between occupational lifting and preterm birth among primigravid women. The study adds to a large body of prospective studies on occupational lifting and adverse pregnancy outcomes by refined exposure assessment. PMID:24614129

  3. Relation of Periodontitis to Risk of Cardiovascular and All-Cause Mortality (from a Danish Nationwide Cohort Study).

    PubMed

    Hansen, Gorm Mørk; Egeberg, Alexander; Holmstrup, Palle; Hansen, Peter Riis

    2016-08-15

    Periodontitis and atherosclerosis are highly prevalent chronic inflammatory diseases, and it has been suggested that periodontitis is an independent risk factor of cardiovascular disease (CVD) and that a causal link may exist between the 2 diseases. Using Danish national registers, we identified a nationwide cohort of 17,691 patients who received a hospital diagnosis of periodontitis within a 15-year period and matched them with 83,003 controls from the general population. We performed Poisson regression analysis to determine crude and adjusted incidence rate ratios of myocardial infarction, ischemic stroke, cardiovascular death, major adverse cardiovascular events, and all-cause mortality. The results showed that patients with periodontitis were at higher risk of all examined end points. The findings remained significant after adjustment for increased baseline co-morbidity in periodontitis patients compared with controls, for example, with adjusted incidence rate ratio 2.02 (95% CI 1.87 to 2.18) for cardiovascular death and 2.70 (95% CI 2.60 to 2.81) for all-cause mortality. Patients with a hospital diagnosis of periodontitis have a high burden of co-morbidity and an increased risk of CVD and all-cause mortality. In conclusion, our results support that periodontitis may be an independent risk factor for CVD. PMID:27372888

  4. Establishment of Intestinal Microbiota during Early Life: a Longitudinal, Explorative Study of a Large Cohort of Danish Infants

    PubMed Central

    Bergström, Anders; Skov, Thomas Hjort; Bahl, Martin Iain; Roager, Henrik Munch; Christensen, Line Brinch; Ejlerskov, Katrine Tschentscher; Mølgaard, Christian; Michaelsen, Kim F.

    2014-01-01

    Fecal samples were obtained from a cohort of 330 healthy Danish infants at 9, 18, and 36 months after birth, enabling characterization of interbacterial relationships by use of quantitative PCR targeting 31 selected bacterial 16S rRNA gene targets representing different phylogenetic levels. Nutritional parameters and measures of growth and body composition were determined and investigated in relation to the observed development in microbiota composition. We found that significant changes in the gut microbiota occurred, particularly from age 9 to 18 months, when cessation of breastfeeding and introduction of a complementary feeding induce replacement of a microbiota characterized by lactobacilli, bifidobacteria, and Enterobacteriaceae with a microbiota dominated by Clostridium spp. and Bacteroides spp. Classification of samples by a proxy enterotype based on the relative levels of Bacteroides spp. and Prevotella spp. showed that enterotype establishment occurs between 9 and 36 months. Thirty percent of the individuals shifted enterotype between 18 and 36 months. The composition of the microbiota was most pronouncedly influenced by the time of cessation of breastfeeding. From 9 to 18 months, a positive correlation was observed between the increase in body mass index and the increase of the short-chain-fatty-acid-producing clostridia, the Clostridum leptum group, and Eubacterium hallii. Considering previously established positive associations between rapid infant weight gain, early breastfeeding discontinuation, and later-life obesity, the corresponding microbial findings seen here warrant attention. PMID:24584251

  5. International travel and the risk of hospitalization with non-typhoidal Salmonella bacteremia. A Danish population-based cohort study, 1999-2008

    PubMed Central

    2011-01-01

    Background Information is sparse regarding the association between international travel and hospitalization with non-typhoidal Salmonella bacteremia. The aim of this study was to determine the proportion, risk factors and outcomes of travel-related non-typhoidal Salmonella bacteremia. Methods We conducted a 10-year population-based cohort study of all patients hospitalized with non-typhoidal Salmonella bacteremia in three Danish counties (population 1.6 million). We used denominator data on Danish travellers to assess the risk per 100,000 travellers according to age and travel destination. We used patients contemporaneously diagnosed with travel-related Salmonella gastroenteritis as reference patients to estimate the relative risk of presenting with travel-related bacteremia as compared with gastroenteritis. To evaluate clinical outcomes, we compared patients with travel-related bacteremia and patients with domestically acquired bacteremia in terms of length of hospital stay, number of extraintestinal focal infections and mortality after 30 and 90 days. Results We identified 311 patients hospitalized with non-typhoidal Salmonella bacteremia of whom 76 (24.4%) had a history of international travel. The risk of travel-related bacteremia per traveller was highest in the age groups 15-24 years (0.8/100,000 travellers) and 65 years and above (1.2/100,000 travellers). The sex- and age-adjusted relative risk of presenting with bacteremia was associated with travel to Sub-Saharan Africa (odds ratio 18.4; 95% confidence interval [6.9-49.5]), the Middle East (10.6; [2.1-53.2]) and South East Asia (4.0; [2.2-7.5]). We found high-risk countries in the same three regions when estimating the risk per traveller according to travel destination. Patients hospitalized with travel-related bacteremia had better clinical outcomes than patients with domestically acquired bacteremia, they had a shorter length of hospital stay (8 vs. 11 days), less extraintestinal focal infections (5 vs

  6. Life Expectancy in Patients Treated for Osteoporosis: Observational Cohort Study Using National Danish Prescription Data.

    PubMed

    Abrahamsen, Bo; Osmond, Clive; Cooper, Cyrus

    2015-09-01

    Osteoporosis is a chronic disease, carrying an elevated risk of fractures, morbidity, and death. Long-term treatment may be required, but the long-term risks with osteoporosis drugs remain incompletely understood. The competing risk of death may be a barrier to treating the oldest, yet this may not be rational if the risk of death is reduced by treatment. It is difficult to devise goal-directed long-term strategies for managing osteoporosis without firm information about residual life expectancy in treated patients. We conducted an observational study in Danish national registries tracking prescriptions for osteoporosis drugs, comorbid conditions, and deaths. We included 58,637 patients and 225,084 age- and sex-matched control subjects. Information on deaths until the end of 2013 was retrieved, providing a follow-up period of 10 to 17 years. In men younger than 80 years and women younger than 60 years, the relative risk of dying declined from being strongly increased in the first year to a stable but elevated level in subsequent years. In women older than 65 to 70 years, there was only a small elevation in risk in the first year of treatment followed by lower than background population mortality. The residual life expectancy of a 50-year-old man beginning osteoporosis treatment was estimated to be 18.2 years and that of a 75-year-old man was 7.5 years. Estimates in women were 26.4 years and 13.5 years, respectively. This study shows an excess mortality in men and in women younger than 70 years who are treated for osteoporosis compared with the background population. This excess risk is more pronounced in the first few years on treatment. The average life expectancy of osteoporosis patients is in excess of 15 years in women younger than 75 years and in men younger than 60 years, highlighting the importance of developing tools for long-term management. PMID:25663501

  7. Hospital work and pregnancy outcomes: a study in the Danish National Birth Cohort.

    PubMed

    Suárez-Varela, María M Morales; Kaerlev, Linda; Zhu, Jin Liang; Bonde, Jens Peter; Nøhr, Ellen-Aagaard; Llopis-González, Agustín; Olsen, Jørn

    2009-01-01

    In hospitals, women of reproductive age do a range of work tasks, some of which are known to carry potential risks. Tasks such as working with radiation, chemicals, and infectious agents, as well as performing heavy lifting or tasks requiring erratic sleep patterns have been reported to increase the risk of reproductive failures. Our aim was to study pregnancy outcomes in female hospital workers in Denmark. We performed a cohort study of 5976 female hospital workers and used as a reference group 60,890 women employed outside of hospitals. The reproductive health of hospital workers working during pregnancy is comparable to those of non-hospital workers for the majority of reproductive failures studied. However, an increased prevalence of congenital abnormalities was noted in some subgroups of hospital workers, which may indicate that some hospital work still entails fetotoxic hazards. PMID:19886351

  8. Psychiatric Diagnoses in Individuals with Non-Syndromic Oral Clefts: A Danish Population-Based Cohort Study

    PubMed Central

    Pedersen, Dorthe Almind; Wehby, George L.; Murray, Jeffrey C.; Christensen, Kaare

    2016-01-01

    Background The aim of this study was to investigate the risk of psychiatric diagnoses in individuals with non-syndromic oral clefts (OC) compared with individuals without OC, including ages from 1 to 76 years. Methods Linking four Danish nationwide registers, we investigated the risk of psychiatric diagnoses at Danish psychiatric hospitals during the period 1969–2012 for individuals born with non-syndromic OC in Denmark 1936–2009 compared with a cohort of 10 individuals without OC per individual with OC, matched by sex and birth year. The sample included 8,568 individuals with OC, observed for 247,821 person-years, and 85,653 individuals without OC followed for 2,501,129 person-years. Results A total of 953 (11.1%) of the individuals with OC (9.6% for cleft lip (CL), 10.8% for cleft lip and palate (CLP) and 13.1% for cleft palate (CP)) and 8,117 (9.5%) in the comparison group had at least one psychiatric diagnosis. Cox proportional hazard regression model revealed that individuals with OC had significantly higher risk of a psychiatric diagnosis (hazard ratio (HR) = 1.19, 95% CI: 1.12–1.28). When examining cleft type, no difference was found for CL (HR = 1.03, 95% CI: 0.90–1.17), but CLP was associated with a small increased risk (HR = 1.13, 95% CI: 1.01–1.26), whereas individuals with CP had the largest increased risk (HR = 1.45, 95% CI: 1.30–1.62). The largest differences were found in schizophrenia-like disorders, mental retardation and pervasive developmental disorders, but we found no increased risk of mood disorders and anxiety-related disorders. Conclusion Individuals with non-syndromic OC had significantly higher risk of psychiatric diagnoses compared with individuals without OC. However, the elevated risk was observed for individuals with CLP and CP but not for individuals with CL and the absolute risk increase was modest. PMID:27223812

  9. Validation of the Novaco Anger Scale-Provocation Inventory (Danish) With Nonclinical, Clinical, and Offender Samples.

    PubMed

    Moeller, Stine Bjerrum; Novaco, Raymond W; Heinola-Nielsen, Vivian; Hougaard, Helle

    2016-10-01

    Anger has high prevalence in clinical and forensic settings, and it is associated with aggressive behavior and ward atmosphere on psychiatric units. Dysregulated anger is a clinical problem in Danish mental health care systems, but no anger assessment instruments have been validated in Danish. Because the Novaco Anger Scale and Provocation Inventory (NAS-PI) has been extensively validated with different clinical populations and lends itself to clinical case formulation, it was selected for translation and evaluation in the present multistudy project. Psychometric properties of the NAS-PI were investigated with samples of 477 nonclinical, 250 clinical, 167 male prisoner, and 64 male forensic participants. Anger prevalence and its relationship with other anger measures, anxiety/depression, and aggression were examined. NAS-PI was found to have high reliability, concurrent validity, and discriminant validity, and its scores discriminated the samples. High scores in the offender group demonstrated the feasibility of obtaining self-report assessments of anger with this population. Retrospective and prospective validity of the NAS were tested with the forensic patient sample regarding physically aggressive behavior in hospital. Regression analyses showed that higher scores on NAS increase the risk of having acted aggressively in the past and of acting aggressively in the future. PMID:25934160

  10. Lung cancer, smoking, and environment: a cohort study of the Danish population.

    PubMed Central

    Engholm, G.; Palmgren, F.; Lynge, E.

    1996-01-01

    OBJECTIVE--The almost twofold difference in lung cancer incidence between people living in Copenhagen and in rural area of Denmark in the 1980s led to public concern; this study was undertaken to assess the effects of air pollution and occupation on lung cancer in Denmark, with control for smoking habits. DESIGN--Cohort study of national population. SUBJECTS--People aged 30-64 and economically active in 1970 (927,470 men and 486,130 women). MAIN OUTCOME MEASURES--Relative risks for lung cancer estimated with multiplicative Poisson modelling of incidence rates. RESULTS--Differences in smoking habit explained about 60% of the excess lung cancer risk in Copenhagen for men and 90% for women. After control for smoking, workers had double the lung cancer risk of teachers and academics. There was only a small independent effect of region. CONCLUSION--Smoking is the main factor behind the regional differences in lung cancer incidence in Denmark, and occupational risk factors also seem to have an important role. The outdoor air in Copenhagen around 1970 contained on average 50-80 micrograms/m3 of sulphur dioxide, 80-100 micrograms/m3 total suspended particulate matter, and up to 10 ng/m3 benzo(a)pyrene and had peak values of daily smoke of 120 micrograms/m3. Region had only a small effect on incidence of lung cancer int eh present study, which suggests that an influence of outdoor air pollution on lung cancer is identifiable only above this pollution level. PMID:8634614

  11. Danish singles have a twofold risk of acute coronary syndrome: data from a cohort of 138 290 persons

    PubMed Central

    Nielsen, K M; Faergeman, O; Larsen, M L; Foldspang, A

    2006-01-01

    Study objective Atherosclerosis of the coronary and other arteries is an important health problem in virtually all countries of the world, and thus there is a persisting need for the development of preventive programmes including population risk group identification. The aim of the study was to identify sociodemographic population risk indicators of an initial episode of acute coronary syndrome (ACS), including unstable angina pectoris (UAP), myocardial infarction (MI), and sudden cardiac death (SCD). Design Cohort study of 138 290 residents of the municipality of Aarhus, Denmark, aged 30–69 years. Information on population members' individual age, sex, social background, and eventual death was obtained from Danish Population Registers. Setting University hospital. Patients The study prospectively identified 646 victims of ACS from 1 April 2000 to 31 March 2002. Main results Based on multiple logistic regression, age and single living were found to be positively associated with incident ACS in both sexes. Women >60 years living alone and men >50 years living alone were at especially high risk. They constituted only 5.4% and 7.7% of the source population, respectively, but they accounted for 34.3% and 62.4% of ACS patients dying within 30 days. Conclusions Single living is associated with an increased risk of ACS. Thus, risk groups identified by use of information on their age and family structure may be targets for future more focused and cost effective preventive strategies. In Western populations, such high risk groups will constitute comparatively limited parts of the population, and in Denmark they are easily identifiable in routine population registers. PMID:16840763

  12. Cesarean Section and Rate of Subsequent Stillbirth, Miscarriage, and Ectopic Pregnancy: A Danish Register-Based Cohort Study

    PubMed Central

    O'Neill, Sinéad M.; Agerbo, Esben; Kenny, Louise C.; Henriksen, Tine B.; Kearney, Patricia M.; Greene, Richard A.; Mortensen, Preben Bo; Khashan, Ali S.

    2014-01-01

    Background With cesarean section rates increasing worldwide, clarity regarding negative effects is essential. This study aimed to investigate the rate of subsequent stillbirth, miscarriage, and ectopic pregnancy following primary cesarean section, controlling for confounding by indication. Methods and Findings We performed a population-based cohort study using Danish national registry data linking various registers. The cohort included primiparous women with a live birth between January 1, 1982, and December 31, 2010 (n = 832,996), with follow-up until the next event (stillbirth, miscarriage, or ectopic pregnancy) or censoring by live birth, death, emigration, or study end. Cox regression models for all types of cesarean sections, sub-group analyses by type of cesarean, and competing risks analyses for the causes of stillbirth were performed. An increased rate of stillbirth (hazard ratio [HR] 1.14, 95% CI 1.01, 1.28) was found in women with primary cesarean section compared to spontaneous vaginal delivery, giving a theoretical absolute risk increase (ARI) of 0.03% for stillbirth, and a number needed to harm (NNH) of 3,333 women. Analyses by type of cesarean section showed similarly increased rates for emergency (HR 1.15, 95% CI 1.01, 1.31) and elective cesarean (HR 1.11, 95% CI 0.91, 1.35), although not statistically significant in the latter case. An increased rate of ectopic pregnancy was found among women with primary cesarean overall (HR 1.09, 95% CI 1.04, 1.15) and by type (emergency cesarean, HR 1.09, 95% CI 1.03, 1.15, and elective cesarean, HR 1.12, 95% CI 1.03, 1.21), yielding an ARI of 0.1% and a NNH of 1,000 women for ectopic pregnancy. No increased rate of miscarriage was found among women with primary cesarean, with maternally requested cesarean section associated with a decreased rate of miscarriage (HR 0.72, 95% CI 0.60, 0.85). Limitations include incomplete data on maternal body mass index, maternal smoking, fertility treatment, causes of

  13. Attention Deficit/Hyperactivity Disorder and Childhood Autism in Association with Prenatal Exposure to Perfluoroalkyl Substances: A Nested Case–Control Study in the Danish National Birth Cohort

    PubMed Central

    Liew, Zeyan; Ritz, Beate; von Ehrenstein, Ondine S.; Bech, Bodil Hammer; Nohr, Ellen Aagaard; Fei, Chunyuan; Bossi, Rossana; Henriksen, Tine Brink; Bonefeld-Jørgensen, Eva Cecilie

    2014-01-01

    Background: Perfluoroalkyl substances (PFASs) are persistent pollutants found to be endocrine disruptive and neurotoxic in animals. Positive correlations between PFASs and neurobehavioral problems in children were reported in cross-sectional data, but findings from prospective studies are limited. Objectives: We investigated whether prenatal exposure to PFASs is associated with attention deficit/hyperactivity disorder (ADHD) or childhood autism in children. Methods: Among 83,389 mother–child pairs enrolled in the Danish National Birth Cohort during 1996–2002, we identified 890 ADHD cases and 301 childhood autism cases from the Danish National Hospital Registry and the Danish Psychiatric Central Registry. From this cohort, we randomly selected 220 cases each of ADHD and autism, and we also randomly selected 550 controls frequency matched by child’s sex. Sixteen PFASs were measured in maternal plasma collected in early or mid-pregnancy. We calculated risk ratios (RRs) using generalized linear models, taking into account sampling weights. Results: Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were detected in all samples; four other PFASs were quantified in ≥ 90% of the samples. We did not find consistent evidence of associations between mother’s PFAS plasma levels and ADHD [per natural log nanograms per milliliter increase: PFOS RR = 0.87 (95% CI: 0.74, 1.02); PFOA RR = 0.98 (95% CI: 0.82, 1.16)] or autism [per natural log nanograms per milliliter increase: PFOS RR = 0.92 (95% CI: 0.69, 1.22); PFOA RR = 0.98 (95% CI: 0.73, 1.31)]. We found positive as well as negative associations between higher PFAS quartiles and ADHD in models that simultaneously adjusted for all PFASs, but these estimates were imprecise. Conclusions: In this study we found no consistent evidence to suggest that prenatal PFAS exposure increases the risk of ADHD or childhood autism in children. Citation: Liew Z, Ritz B, von Ehrenstein OS, Bech BH, Nohr EA, Fei CY

  14. Existing data sources for clinical epidemiology: The Danish National Database of Reimbursed Prescriptions

    PubMed Central

    Johannesdottir, Sigrun Alba; Horváth-Puhó, Erzsébet; Ehrenstein, Vera; Schmidt, Morten; Pedersen, Lars; Sørensen, Henrik Toft

    2012-01-01

    The Danish health care system provides partial reimbursement of most prescription medications in Denmark. The dispensation of prescription medications is registered in administrative databases. Each time a prescription is redeemed at a pharmacy, an electronic record is generated with information related to the user, prescriber, the pharmacy, and the dispensed drug. The National Health Service gathers this information for administration of the drug reimbursement plan. Recently, this information became the basis for the establishment of a new research database, the Danish National Database of Reimbursed Prescriptions (DNDRP). In this paper, we review the content, coverage, quality, linkage, access, and research possibilities of this new database. The database encompasses the reimbursement records of all reimbursed drugs sold in community pharmacies and hospital-based outpatient pharmacies in Denmark since 2004. On average, approximately 3.5 million users are recorded in the database each year. During the coverage period, the number of annual prescription redemptions increased by 15%. Most dispensed prescriptions are in the categories “alimentary tract and metabolism”, “cardiovascular system”, “nervous system”, and “respiratory system”. Individuals are identified by the unique central personal registration (CPR) number assigned to all persons born in or immigrating to Denmark. The new database fully complies with Denmark’s Act on Processing of Personal Data, while avoiding additional restrictions imposed on data use at the Danish National Prescription Registry, administered by Statistics Denmark. Most importantly, CPR numbers are reversibly encrypted, which allows re-identification of drug users; furthermore, the data access is possible outside the servers of Statistics Denmark. These features open additional opportunities for international collaboration, validation studies, studies on adverse drug effects requiring review of medical records, studies

  15. Physical and emotional well-being of survivors of childhood and young adult allo-SCT - A Danish national cohort study.

    PubMed

    Jensen, Josef Nathan; Gøtzsche, Frederik; Heilmann, Carsten; Sengeløv, Henrik; Adamsen, Lis; Christensen, Karl Bang; Larsen, Hanne Baekgaard

    2016-08-01

    The aim of this investigation was to examine, within a population-based study of a national cohort comprising Danish survivors of allo-SCT (n = 148), the long-term effects of allo-SCT in children and young adults. Physical and emotional well-being was assessed using the Short Form 36 (SF-36) and the HADS. Allo-SCT-related data were obtained from the participants' medical records. The study includes 148 patients, with an 89% response rate (n = 132). For comparison purposes, norm data from Danish (1994, n = 6000), Swedish (2006, n = 285), and British (2001, n = 1792) population samples were used. Factors negatively influencing the SF-36 subscales included female gender; TBI; stem cells derived from PB; older age at time of questioning; and living alone. Factors significantly (p < 0.05) influencing HADS were transplantation with stem cells derived from PB and being underweight at time of questioning (median values were within normal range). Overall scores of allo-SCT patients were similar to norm data. In conclusion, this national cohort study shows that patients treated with SCT in early life (<25) and whose survival period extended beyond 10 yr (mean) from SCT, showed similar levels of anxiety, depression, and physical and emotional well-being to those of the normal population. PMID:27231147

  16. Is the clinical course of HIV-1 changing? Cohort study.

    PubMed Central

    Sinicco, A.; Fora, R.; Raiteri, R.; Sciandra, M.; Bechis, G.; Calvo, M. M.; Gioannini, P.

    1997-01-01

    OBJECTIVE: To assess whether the clinical course of HIV infection has changed from 1985 to 1995. DESIGN: Cohort Study. SETTING: Infectious disease clinic. SUBJECTS: 285 patients recruited from September 1985 to January 1995 with < or = 12 months between the dates of their last seronegative and first seropositive test result and with first follow up visit in the six months after seroconversion and at least 12 months' follow up. Patients were grouped according to the date of seroconversion. MAIN OUTCOME MEASURES: Time to CD4 cell count of < 500, 400, and 200 x 10(6) cells/l, and clinical outcome defining AIDS; variation in cell count per day between consecutive visits, and ratio between this variation and time from estimated date of seroconversion at each visit. RESULTS: The groups were similar in age, number with acute primary HIV infection, CD4 cell count at intake, and cell count at the beginning of antiretroviral treatment; they differed in sex ratio, risk factors for HIV, probability of CD4 cell decline to < 500, 400, and 200 x 10(6) cells/l. and risk of developing AIDS. Acute infection, seroconversion after December 1989, and serum beta 2 microglobulin > 296 nmol/l were independent predictors of poor clinical course. The speed of CD4 cell decline, expressed as cell variation divided by the number of days between consecutive visits, increased with more recent seroconversion (P = 0.02). Ratio between the speed of CD4 cell decline and time from estimated date of seroconversion at each visit was also higher in the patients who seroconverted after December 1989. CONCLUSIONS: The faster disease progression and the higher speed of CD4 cell decline at early stages in the patients with recently acquired HIV infection suggest changes in the clinical course of HIV infection. PMID:9154026

  17. Validity of Childhood Autism in the Danish Psychiatric Central Register: Findings from a Cohort Sample Born 1990-1999

    ERIC Educational Resources Information Center

    Lauritsen, Marlene B.; Jorgensen, Meta; Madsen, Kreesten M.; Lemcke, Sanne; Toft, Susanne; Grove, Jakob; Schendel, Diana E.; Thorsen, Poul

    2010-01-01

    The purpose of this study was to assess the validity of the diagnosis of childhood autism in the Danish Psychiatric Central Register (DPCR) by reviewing medical records from 499 of 504 total children with childhood autism born 1990-1999. Based on review of abstracted behaviors recorded in case records from child psychiatric hospitals, case status…

  18. Epilepsy in Individuals with a History of Asperger's Syndrome: A Danish Nationwide Register-Based Cohort Study

    ERIC Educational Resources Information Center

    Mouridsen, Svend Erik; Rich, Bente; Isager, Torben

    2013-01-01

    We performed a nationwide, register-based retrospective follow-up study of epilepsy in all people who were born between January 1, 1980 and June 29, 2006 and registered in the Danish Psychiatric Central Register with Asperger's syndrome on February 7, 2011. All 4,180 identified cases with AS (3,431 males and 749 females) were screened through the…

  19. Epilepsy in individuals with a history of Asperger's syndrome: a Danish nationwide register-based cohort study.

    PubMed

    Mouridsen, Svend Erik; Rich, Bente; Isager, Torben

    2013-06-01

    We performed a nationwide, register-based retrospective follow-up study of epilepsy in all people who were born between January 1, 1980 and June 29, 2006 and registered in the Danish Psychiatric Central Register with Asperger's syndrome on February 7, 2011. All 4,180 identified cases with AS (3,431 males and 749 females) were screened through the nationwide Danish National Hospital Register (DNHR) with respect to epilepsy. Mean age at follow-up was 18.1 years (range 4-31 years). Of the 4,180 individuals with AS, 164 (3.9%) were registered with at least one epilepsy diagnosis in the DNHR, which is significantly increased (p < 0.0001) relative to the same age group in the general population, where an estimate is about 2.0%. PMID:23054204

  20. Predicted vitamin D status during pregnancy in relation to offspring forearm fractures in childhood: a study from the Danish National Birth Cohort.

    PubMed

    Petersen, Sesilje B; Strøm, Marin; Maslova, Ekaterina; Granström, Charlotta; Vestergaard, Peter; Mølgaard, Christian; Olsen, Sjurdur F

    2015-12-14

    In a prospective cohort study, the association between maternal vitamin D status during pregnancy and offspring forearm fractures during childhood and adolescence was analysed in 30 132 mother and child pairs recruited to the Danish National Birth Cohort between 1996 and 2002. Data on characteristics, dietary factors and lifestyle factors were collected on several occasions during pregnancy. We analysed the association between predicted vitamin D status, based on a subsample with 25-hydroxyvitamin D (25(OH)D) biomarker measurements (n 1497) from gestation week 25, and first-time forearm fractures among offspring between birth and end of follow-up. Diagnoses were extracted from the Danish National Patient Register. Multivariable Cox regression models using age as the underlying time scale indicated no overall association between predicted vitamin D status (based on smoking, season, dietary and supplementary vitamin D intake, tanning bed use and outdoor physical activity) in pregnancy and offspring forearm fractures. Likewise, measured 25(OH)D, tanning bed use and dietary vitamin D intake were not associated with offspring forearm fractures. In mid-pregnancy, 91 % of the women reported intake of vitamin D from dietary supplements. Offspring of women who took >10 µg/d in mid-pregnancy had a significantly increased risk for fractures compared with the reference level of zero intake (hazard ratios (HR) 1·31; 95% CI 1·06, 1·62), but this was solely among girls (HR 1·48; 95% CI 1·10, 2·00). Supplement use in the peri-conceptional period exhibited similar pattern, although not statistically significant. In conclusion, our data indicated no protective effect of maternal vitamin D status with respect to offspring forearm fractures. PMID:26431383

  1. Use of β-Blockers, Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Risk of Breast Cancer Recurrence: A Danish Nationwide Prospective Cohort Study

    PubMed Central

    Sørensen, Gitte Vrelits; Ganz, Patricia A.; Cole, Steven W.; Pedersen, Lars A.; Toft Sørensen, Henrik; Cronin-Fenton, Deirdre P.; Peter Garne, Jens; Christiansen, Peer M.; Lash, Timothy L.; Ahern, Thomas P.

    2013-01-01

    Purpose To estimate associations between use of β-blockers, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers (ARBs) and breast cancer recurrence in a large Danish cohort. Patients and Methods We enrolled 18,733 women diagnosed with nonmetastatic breast cancer between 1996 and 2003. Patient, treatment, and 10-year recurrence data were ascertained from the Danish Breast Cancer Cooperative Group registry. Prescription and medical histories were ascertained by linkage to the National Prescription Registry and Registry of Patients, respectively. β-Blocker exposure was defined in aggregate and according to solubility, receptor selectivity, and individual drugs. ACE inhibitor and ARB exposures were defined in aggregate. Recurrence associations were estimated with multivariable Cox regression models in which time-varying drug exposures were lagged by 1 year. Results Compared with never users, users of any β-blocker had a lower recurrence hazard in unadjusted models (unadjusted hazard ratio [HR] = 0.91; 95% CI, 0.81 to 1.0) and a slightly higher recurrence hazard in adjusted models (adjusted HR = 1.3; 95% CI, 1.1 to 1.5). Associations were similar for exposures defined by receptor selectivity and solubility. Although most individual β-blockers showed no association with recurrence, metoprolol and sotalol were associated with increased recurrence rates (adjusted metoprolol HR = 1.5, 95% CI, 1.2 to 1.8; adjusted sotalol HR = 2.0, 95% CI, 0.99 to 4.0). ACE inhibitors were associated with a slightly increased recurrence hazard, whereas ARBs were not associated with recurrence (adjusted ACE inhibitor HR = 1.2, 95% CI, 0.97 to 1.4; adjusted ARBs HR = 1.1, 95% CI, 0.85 to 1.3). Conclusion Our data do not support the hypothesis that β-blockers attenuate breast cancer recurrence risk. PMID:23650417

  2. The UK clinical aptitude test and clinical course performance at Nottingham: a prospective cohort study

    PubMed Central

    2013-01-01

    Background The UK Clinical Aptitude Test (UKCAT) was introduced in 2006 as an additional tool for the selection of medical students. It tests mental ability in four distinct domains (Verbal Reasoning, Quantitative Reasoning, Abstract Reasoning, and Decision Analysis), and the results are available to students and admission panels in advance of the selection process. Our first study showed little evidence of any predictive validity for performance in the first two years of the Nottingham undergraduate course. The study objective was to determine whether the UKCAT scores had any predictive value for the later parts of the course, largely delivered via clinical placements. Methods Students entering the course in 2007 and who had taken the UKCAT were asked for permission to use their anonymised data in research. The UKCAT scores were incorporated into a database with routine pre-admission socio-demographics and subsequent course performance data. Correlation analysis was followed by hierarchical multivariate linear regression. Results The original study group comprised 204/254 (80%) of the full entry cohort. With attrition over the five years of the course this fell to 185 (73%) by Year 5. The Verbal Reasoning score and the UKCAT Total score both demonstrated some univariate correlations with clinical knowledge marks, and slightly less with clinical skills. No parts of the UKCAT proved to be an independent predictor of clinical course marks, whereas prior attainment was a highly significant predictor (p <0.001). Conclusions This study of one cohort of Nottingham medical students showed that UKCAT scores at admission did not independently predict subsequent performance on the course. Whilst the test adds another dimension to the selection process, its fairness and validity in selecting promising students remains unproven, and requires wider investigation and debate by other schools. PMID:23442227

  3. A Study of the Combined Effects of Physical Activity and Air Pollution on Mortality in Elderly Urban Residents: The Danish Diet, Cancer, and Health Cohort

    PubMed Central

    de Nazelle, Audrey; Mendez, Michelle Ann; Garcia-Aymerich, Judith; Hertel, Ole; Tjønneland, Anne; Overvad, Kim; Raaschou-Nielsen, Ole; Nieuwenhuijsen, Mark J.

    2015-01-01

    Background Physical activity reduces, whereas exposure to air pollution increases, the risk of premature mortality. Physical activity amplifies respiratory uptake and deposition of air pollutants in the lung, which may augment acute harmful effects of air pollution during exercise. Objectives We aimed to examine whether benefits of physical activity on mortality are moderated by long-term exposure to high air pollution levels in an urban setting. Methods A total of 52,061 subjects (50–65 years of age) from the Danish Diet, Cancer, and Health cohort, living in Aarhus and Copenhagen, reported data on physical activity in 1993–1997 and were followed until 2010. High exposure to air pollution was defined as the upper 25th percentile of modeled nitrogen dioxide (NO2) levels at residential addresses. We associated participation in sports, cycling, gardening, and walking with total and cause-specific mortality by Cox regression, and introduced NO2 as an interaction term. Results In total, 5,534 subjects died: 2,864 from cancer, 1,285 from cardiovascular disease, 354 from respiratory disease, and 122 from diabetes. Significant inverse associations of participation in sports, cycling, and gardening with total, cardiovascular, and diabetes mortality were not modified by NO2. Reductions in respiratory mortality associated with cycling and gardening were more pronounced among participants with moderate/low NO2 [hazard ratio (HR) = 0.55; 95% CI: 0.42, 0.72 and 0.55; 95% CI: 0.41, 0.73, respectively] than with high NO2 exposure (HR = 0.77; 95% CI: 0.54, 1.11 and HR = 0.81; 95% CI: 0.55, 1.18, p-interaction = 0.09 and 0.02, respectively). Conclusions In general, exposure to high levels of traffic-related air pollution did not modify associations, indicating beneficial effects of physical activity on mortality. These novel findings require replication in other study populations. Citation Andersen ZJ, de Nazelle A, Mendez MA, Garcia-Aymerich J, Hertel O, Tjønneland A, Overvad

  4. A retrospective study of clinical and mutational findings in 45 Danish families with ectodermal dysplasia.

    PubMed

    Tiedemann Svendsen, Mathias; Henningsen, Emil; Hertz, Jens Michael; Vestergaard Grejsen, Dorthe; Bygum, Anette

    2014-09-01

    Ectodermal dysplasias form a complex, nosologic group of diseases with defects in at least 2 ectodermal structures. A retrospective study of patients with ectodermal dysplasia seen at our department over a period of 19 years (1994-2013) was performed. The study population consisted of 67 patients covering 17 different diagnoses. Forty-five families were identified of which 26 were sporadic cases with no affected family members. In 27 tested families a disease-causing mutation was identified in 23 families. Eleven mutations were novel mutations. To our knowledge, we present the first large ectodermal dysplasia cohort focusing on clinical manifestations in combination with mutational analysis. We recommend a nationwide study to estimate the prevalence of the ectodermal dysplasia and to ensure relevant molecular genetic testing which may form the basis of a national ectodermal dysplasia database. PMID:24514865

  5. Frailty phenotypes in the elderly based on cluster analysis: a longitudinal study of two Danish cohorts. Evidence for a genetic influence on frailty.

    PubMed

    Dato, Serena; Montesanto, Alberto; Lagani, Vincenzo; Jeune, Bernard; Christensen, Kaare; Passarino, Giuseppe

    2012-06-01

    Frailty is a physiological state characterized by the deregulation of multiple physiologic systems of an aging organism determining the loss of homeostatic capacity, which exposes the elderly to disability, diseases, and finally death. An operative definition of frailty, useful for the classification of the individual quality of aging, is needed. On the other hand, the documented heterogeneity in the quality of aging among different geographic areas suggests the necessity for a frailty classification approach providing population-specific results. Moreover, the contribution of the individual genetic background on the frailty status is still questioned. We investigated the applicability of a cluster analysis approach based on specific geriatric parameters, previously set up and validated in a southern Italian population, to two large longitudinal Danish samples. In both cohorts, we identified groups of subjects homogeneous for their frailty status and characterized by different survival patterns. A subsequent survival analysis availing of Accelerated Failure Time models allowed us to formulate an operative index able to correlate classification variables with survival probability. From these models, we quantified the differential effect of various parameters on survival, and we estimated the heritability of the frailty phenotype by exploiting the twin pairs in our sample. These data suggest the presence of a genetic influence on the frailty variability and indicate that cluster analysis can define specific frailty phenotypes in each population. PMID:21567248

  6. Surveillance of Hospital Contacts among Danish Seafarers and Fishermen with Focus on Skin and Infectious Diseases—A Population-Based Cohort Study

    PubMed Central

    Kaerlev, Linda; Jensen, Anker; Hannerz, Harald

    2014-01-01

    Objectives: A systematic overview of time trends in hospital contacts among Danish seafarers and fishermen by job title and analyses on skin and infectious diseases. Methods: Occupational cohorts with hospital contacts 1994–1998 and 1999–2003. Standardized hospital contact ratios (SHCR) were estimated using national rates and ranked by SHCR size. Results: For non-officers in 1994–1998, infectious diseases had the highest SHCR, followed by neoplastic and endocrinal diseases; in 1999–2003 skin diseases were followed by endocrinal and gastrointestinal diseases. For fishermen in 1994–1998, nervous system, gastrointestinal, and skin diseases had the highest SHCRs; in 1999–2003 it was nervous system, skin, and lymphohematopoietic diseases. As for skin diseases, male fishermen and non-officer seamen generally had increased SHCRs, but engine room personnel specifically had a low SHCR for eczema (eight cases). Fishermen had high SHCRs for tuberculosis in both time periods (six and nine cases, respectively). Non-officer seamen on cargo ships had increased SHCRs for HIV in both time periods and for hepatitis in 1994–1999. Extending the follow-up until 2000 or 2005 showed similar results. Conclusions: Surveillance of seamen’s health gives useful information. The elevated SHCR for HIV infection among non-officers has not declined despite preventive information campaigns. Tuberculosis among fishermen may be due to infection on shore. Skin diseases had very high SHCRs, not due to cutaneous oil exposure. PMID:25411726

  7. General practitioners’ home visit tendency and readmission-free survival after COPD hospitalisation: a Danish nationwide cohort study

    PubMed Central

    Lykkegaard, Jesper; Larsen, Pia V; Paulsen, Maja S; Søndergaard, Jens

    2014-01-01

    Background: The tendency of general practitioners (GPs) to conduct home visits is considered an important aspect of practices’ accessibility and quality of care. Aims: To investigate whether GPs’ tendency to conduct home visits affects 30-day readmission or death after hospitalisation with chronic obstructive pulmonary disease. Methods: All Danish patients first-time hospitalised with COPD during the years 2006–2008 were identified. The association between the GP’s tendency to conduct home visits and the time from hospital discharge until death or all-cause readmission was analysed by means of Cox regression adjusted for multiple patient and practice characteristics. Results: The study included 14,425 patients listed with 1,389 general practices. Approximately 31% of the patients received a home visit during the year preceding their first COPD hospitalisation, and within 30 days after discharge 19% had been readmitted and 1.6% had died without readmission. A U-shaped dose–response relationship was found between GP home visit tendency and readmission-free survival. The lowest adjusted risk of readmission or death was recorded among patients who were listed with a general practice in which >20–30% of other listed first-time COPD-hospitalised patients had received a home visit. The risk was higher if either 0% (hazard rate ratio 1.18 (1.01–1.37)) or >60% (hazard rate ratio 1.23 (1.04–1.44)) of the patients had been visited. Conclusion: A moderate GP tendency to conduct home visits is associated with the lowest 30-day risk of COPD readmission or death. A GP’s tendency to conduct home visits should not be used as a unidirectional indicator of the ability to prevent COPD hospital readmissions. PMID:25429436

  8. Short communication: feasibility and acceptability of developing a multisite clinical cohort of transgender people with HIV infection.

    PubMed

    Poteat, Tonia C; Hanna, David B; Althoff, Keri N

    2015-09-01

    Transgender women bear a disproportionate burden of HIV, yet data among this population are not routinely collected in HIV clinical cohorts. Brief surveys and follow-up qualitative interviews were conducted with principal investigators or designated representatives of 17 HIV clinical cohorts to determine the acceptability and feasibility of pooling transgender-specific data from existing HIV clinical cohort studies. Twelve of 17 sites reported that they already collect gender identity data but not consistently. Others were receptive to collecting this information. Many also expressed interest in a study of clinical outcomes among HIV-infected transgender women using pooled data across cohorts. The collection of longitudinal data on transgender people living with HIV is acceptable and feasible for most North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) cohorts. HIV clinical cohort studies should make efforts to include transgender individuals and develop the tools to collect quality data on this high-need population. PMID:26126154

  9. Sex-specific associations between birth weight and adult primary liver cancer in a large cohort of Danish children.

    PubMed

    Zimmermann, Esther; Berentzen, Tina L; Gamborg, Michael; Sørensen, Thorkild I A; Baker, Jennifer L

    2016-03-15

    Whether the prenatal period is critical for the development of adult primary liver cancer (PLC) is sparsely investigated. Recently, attention has been drawn to potential sex-differences in the early origins of adult disease. The association between birth weight and adult PLC, separately in men and women was investigated, using a large cohort of 217,227 children (51% boys), born from 1936 to 1980, from the Copenhagen School Health Records Register, and followed them until 2010 in national registers. Hazard ratios (95% confidence intervals) of PLC (30 years or older) were estimated by Cox regression models stratified by birth cohort. During 5.1 million person-years of follow-up, 185 men and 65 women developed PLC. Sex modified the association between birth weight and adult PLC (p values for interaction = 0.0005). Compared with a sex-specific reference group of birth weights between 3.25 and 3.75 kg, men with birth weights between 2.00 and 3.25 kg and 3.75-5.50 kg, had HRs of 1.48 (1.06-2.05) and 0.85 (0.56-1.28), respectively. Among women the corresponding HRs were 1.71 (0.90-3.29) and 3.43 (1.73-6.82). Associations were similar for hepatocellular carcinoma only, across year of birth, and after accounting for diagnoses of alcohol-related disorders, viral hepatitis and biliary cirrhosis. Prenatal exposures influenced the risk of adult PLC, and the effects at the high birth weight levels appeared to be sex-specific. These findings underscore the importance of considering sex-specific mechanisms in the early origins of adult PLC. PMID:26506514

  10. [Change of Regulatory Requirement on Cohort Grouping and Endpoint Seting for Intervertebral Fusion Device Clinical Trial].

    PubMed

    Guo Xiaolei

    2015-07-01

    Combining technical requirement from main international administration and status quo of China administration, current regulatory requirement on clinical trail of conventional intervertebral fusion devices has been simplified. Cervical, thoracic and lumbar cases can be grouped into the same cohort, and primary endpoints are mainly based on imageology rather than clinical score. This is an attempt to rationally lessen industrial burdensome. PMID:26665950

  11. Associations between Recreational and Commuter Cycling, Changes in Cycling, and Type 2 Diabetes Risk: A Cohort Study of Danish Men and Women

    PubMed Central

    Rasmussen, Martin G.; Grøntved, Anders; Blond, Kim; Overvad, Kim; Tjønneland, Anne; Jensen, Majken K.; Østergaard, Lars

    2016-01-01

    Background Cycling is a recreational activity and mode of commuting with substantial potential to improve public health in many countries around the world. The aim of this study was to examine prospective associations between recreational and commuter cycling, changes in cycling habits, and risk of type 2 diabetes (T2D) in Danish adults from the Diet, Cancer and Health cohort study. Methods and Findings At baseline from 1993 to 1997, 24,623 men and 27,890 women from Denmark, 50–65 y of age and free of T2D and other chronic diseases, underwent a number of assessments, including completing a lifestyle questionnaire also addressing cycling habits. Approximately 5 y later, at a second examination, participants completed a new, updated lifestyle questionnaire. Cox regression was used to estimate hazard ratios (HRs) of incident T2D registered in the Danish National Diabetes Registry, according to recreational and commuter cycling and changes in cycling habits, with adjustment for a priori known T2D risk factors. During 743,245.4 person-years of follow-up (mean follow-up 14.2 y), 6,779 incident cases of T2D were documented. Multivariable adjusted HRs (95% confidence interval [CI]) were 1, 0.87 (0.82, 0.93), 0.83 (0.77, 0.89), 0.80 (0.74, 0.86) and 0.80 (0.74, 0.87) (p for trend = <0.001) for 0, 1–60, 61–150, 151–300, and >300 min/wk of total cycling (recreational and commuter cycling), respectively. In analysis of seasonal cycling, multivariable adjusted HRs (95% CI) were 1, 0.88 (0.83, 0.94), and 0.80 (0.76, 0.85) for non-cyclists, seasonal cyclists (those cycling only in summer or winter), and those cycling during both summer and winter, respectively. How changes in total cycling from baseline to the second examination affected risk was also investigated, and multivariable adjusted HRs (95% CI) were 1, 0.88 (0.78, 1.01), 0.80 (0.69, 0.91), and 0.71 (0.65, 0.77) for non-cyclists and for those who ceased, initiated, or continued cycling between baseline and the

  12. Adherence to a Healthy Nordic Food Index Is Associated with a Lower Risk of Type-2 Diabetes—The Danish Diet, Cancer and Health Cohort Study

    PubMed Central

    Lacoppidan, Sandra Amalie; Kyrø, Cecilie; Loft, Steffen; Helnæs, Anne; Christensen, Jane; Hansen, Camilla Plambeck; Dahm, Christina Catherine; Overvad, Kim; Tjønneland, Anne; Olsen, Anja

    2015-01-01

    Background: Type-2 diabetes (T2D) prevalence is rapidly increasing worldwide. Lifestyle factors, in particular obesity, diet, and physical activity play a significant role in the etiology of the disease. Of dietary patterns, particularly the Mediterranean diet has been studied, and generally a protective association has been identified. However, other regional diets are less explored. Objective: The aim of the present study was to investigate the association between adherence to a healthy Nordic food index and the risk of T2D. The index consists of six food items: fish, cabbage, rye bread, oatmeal, apples and pears, and root vegetables. Methods: Data was obtained from a prospective cohort study of 57,053 Danish men and women aged 50–64 years, at baseline, of whom 7366 developed T2D (median follow-up: 15.3 years). The Cox proportional hazards model was used to assess the association between the healthy Nordic food index and risk of T2D, adjusted for potential confounders. Results: Greater adherence to the healthy Nordic food index was significantly associated with lower risk of T2D after adjusting for potential confounders. An index score of 5−6 points (high adherence) was associated with a statistically significantly 25% lower T2D risk in women (HR: 0.75, 95%CI: 0.61–0.92) and 38% in men (HR: 0.62; 95%CI: 0.53–0.71) compared to those with an index score of 0 points (poor adherence). Conclusion: Adherence to a healthy Nordic food index was found to be inversely associated with risk of T2D, suggesting that regional diets other than the Mediterranean may also be recommended for prevention of T2D. PMID:26506373

  13. Association of fish consumption and dietary intake of marine n-3 PUFA with myocardial infarction in a prospective Danish cohort study.

    PubMed

    Gammelmark, Anders; Nielsen, Michael S; Bork, Christian S; Lundbye-Christensen, Søren; Tjønneland, Anne; Overvad, Kim; Schmidt, Erik B

    2016-07-01

    Several studies have investigated the potential benefits of marine n-3 PUFA in CVD, generally suggesting a lower risk of CHD. However, recent trials have questioned these results. This study investigated the association of fish consumption with dietary intake of marine n-3 PUFA with incident myocardial infarction (MI). In a Danish cohort study, 57 053 subjects between 50 and 64 years of age were enrolled from 1993 to 1997. From national registries, we identified all cases of incident MI. Dietary fish consumption was assessed using a semi-quantitative food questionnaire, including twenty-six questions regarding fish intake. In addition, we calculated the intake of total and individual marine n-3 PUFA. During a median follow-up of 17·0 years, we identified 3089 cases of incident MI. For both men and women, a high intake of fatty fish was inversely related to incident MI. Thus, when comparing the highest and the lowest quintile of fatty fish intake, we found a 12 % lower relative risk of MI in men (hazard ratio (HR) 0·88; 95 % CI 0·77, 1·00) and a 22 % lower relative risk in women (HR 0·78; 95 % CI 0·63, 0·96) after adjustments. For women, similar associations were observed for individual and total marine n-3 PUFA. In contrast, intake of lean fish was not associated with MI. In conclusion, incident MI was inversely related to a high intake of fatty fish, but not lean fish. However, test for trends across quintiles was not statistically significant. In general, this study supports the view that consumption of fatty fish may protect against MI. PMID:27189437

  14. Existing data sources for clinical epidemiology: the Danish Patient Compensation Association database

    PubMed Central

    Tilma, Jens; Nørgaard, Mette; Mikkelsen, Kim Lyngby; Johnsen, Søren Paaske

    2015-01-01

    Any patient in the Danish health care system who experiences a treatment injury can make a compensation claim to the Danish Patient Compensation Association (DPCA) free of charge. The aim of this paper is to describe the DPCA database as a source of data for epidemiological research. Data to DPCA are collected prospectively on all claims and include information on patient factors and health records, system factors, and administrative data. Approval of claims is based on injury due to the principle of treatment below experienced specialist standard or intolerable, unexpected extensiveness of injury. Average processing time of a compensation claim is 6–8 months. Data collection is nationwide and started in 1992. The patient’s central registration system number, a unique personal identifier, allows for data linkage to other registries such as the Danish National Patient Registry. The DPCA data are accessible for research following data usage permission and make it possible to analyze all claims or specific subgroups to identify predictors, outcomes, etc. DPCA data have until now been used only in few studies but could be a useful data source in future studies of health care-related injuries. PMID:26229505

  15. Disease Activity in Inflammatory Bowel Disease Is Associated with Increased Risk of Myocardial Infarction, Stroke and Cardiovascular Death – A Danish Nationwide Cohort Study

    PubMed Central

    Kristensen, Søren Lund; Ahlehoff, Ole; Lindhardsen, Jesper; Erichsen, Rune; Jensen, Gunnar Vagn; Torp-Pedersen, Christian; Nielsen, Ole Haagen; Gislason, Gunnar Hilmar; Hansen, Peter Riis

    2013-01-01

    Purpose Chronic inflammatory diseases have been linked to increased risk of atherothrombotic events, but the risk associated with inflammatory bowel disease (IBD) is unclear. We therefore examined the risk of myocardial infarction (MI), stroke, and cardiovascular death in patients with IBD. Methods In a nationwide Danish population-based setting, a cohort of patients with incident IBD between 1996 and 2009 were identified in national registers. Hospitalizations with IBD as primary diagnosis, initiation of biological treatment and dispensed prescriptions of corticosteroids were all used as surrogate markers for disease activity, with flares classified as the first 120 days after diagnosis of IBD, and 120 days after a new corticosteroid prescription, biological treatment or IBD hospitalization, respectively. Continued corticosteroid prescriptions or IBD hospitalizations were defined as persistent activity, and periods free of such events were defined as remissions. Poisson regression was used to examine risk of MI, stroke, and cardiovascular death using a matched population-based comparison cohort as reference Results We identified 20,795 IBD patients with a mean age of 40.3 years that were matched according to age and sex with 199,978 controls. During the study period, there were 365 patients with MI, 454 with stroke, and 778 with cardiovascular death. Patients with IBD had an overall increased risk of MI (rate ratio [RR] 1.17 [95% confidence interval 1.05–1.31]), stroke (RR 1.15 [1.04–1.27], and cardiovascular death (RR 1.35 [1.25–1.45]). During flares and persistent IBD activity the RRs of MI increased to 1.49 (1.16–1.93) and 2.05 (1.58–2.65), the RRs of stroke to 1.53 (1.22–1.92) and 1.55 (1.18–2.04) and for cardiovascular death 2.32 (2.01–2.68) and 2.50 (2.14–2.92). In remission periods, the risk of MI, stroke and cardiovascular death was similar to controls. Conclusion Inflammatory bowel disease is associated with increased risk of MI, stroke

  16. Using large clinical data sets to infer pathogenicity for rare copy number variants in autism cohorts

    PubMed Central

    Moreno-De-Luca, D; Sanders, S J; Willsey, A J; Mulle, J G; Lowe, J K; Geschwind, D H; State, M W; Martin, C L; Ledbetter, D H

    2013-01-01

    Copy number variants (CNVs) have a major role in the etiology of autism spectrum disorders (ASD), and several of these have reached statistical significance in case–control analyses. Nevertheless, current ASD cohorts are not large enough to detect very rare CNVs that may be causative or contributory (that is, risk alleles). Here, we use a tiered approach, in which clinically significant CNVs are first identified in large clinical cohorts of neurodevelopmental disorders (including but not specific to ASD), after which these CNVs are then systematically identified within well-characterized ASD cohorts. We focused our initial analysis on 48 recurrent CNVs (segmental duplication-mediated ‘hotspots') from 24 loci in 31 516 published clinical cases with neurodevelopmental disorders and 13 696 published controls, which yielded a total of 19 deletion CNVs and 11 duplication CNVs that reached statistical significance. We then investigated the overlap of these 30 CNVs in a combined sample of 3955 well-characterized ASD cases from three published studies. We identified 73 deleterious recurrent CNVs, including 36 deletions from 11 loci and 37 duplications from seven loci, for a frequency of 1 in 54; had we considered the ASD cohorts alone, only 58 CNVs from eight loci (24 deletions from three loci and 34 duplications from five loci) would have reached statistical significance. In conclusion, until there are sufficiently large ASD research cohorts with enough power to detect very rare causative or contributory CNVs, data from larger clinical cohorts can be used to infer the likely clinical significance of CNVs in ASD. PMID:23044707

  17. Cliques and Cohesion in a Clinical Psychology Graduate Cohort: A Longitudinal Social Network Analysis

    ERIC Educational Resources Information Center

    Kunze, Kimberley Annette

    2013-01-01

    To date, no published research has utilized social network analysis (SNA) to analyze graduate cohorts in clinical psychology. The purpose of this research is to determine how issues of likability among students correlate with other measures, such as disclosure, health, spiritual maturity, help in projects, familiarity, and ease of providing…

  18. Chronic lymphocytic leukemia: a clinical review including Korean cohorts

    PubMed Central

    Jeon, Young-Woo; Cho, Seok-Goo

    2016-01-01

    Only 5th decade ago, chronic lymphocytic leukemia (CLL) was only recognized as disease group of presenting features like peripheral lymphocytosis, organomegaly including of splenomegaly. As understanding of disease biology and molecular diagnostic tools are getting improved gradually, characterization of variation in CLL’s clinical courses was facilitated, resulting in better risk stratification and targeted treatments. Consequently multiple new targeted agents have been used in treatment of CLL, it makes improved clinical outcome. Rituximab containing chemoimmunotherapy (combination of rituximab, fludarabine, and cyclophosphamide) have shown better overall response rate and progression-free survival on fit patients’ group in front-line setting, result in standard first-line therapeutic option for CLL. Furthermore, after introducing that the B-cell receptor is crucial for the evolution and progression of CLL, emerging treatments targeting highly activated surface antigens and oncogenic signaling pathways have been associated with several successes in recent decades. These include new anti-CD 20 monoclonal antibody (obinutuzumab), the bruton tyrosine kinase inhibitor (ibrutinib), the phosphatidylinositol 3-kinase inhibitor (idelalisib), and B-cell CLL/lymphoma 2 inhibitor (ABT-199 and ABT-263). So, we discuss not only general pathophysiology of CLL, but also rapidly advancing treatment strategies that are being studied or approved for treatment of CLL. PMID:27044858

  19. Chronic lymphocytic leukemia: a clinical review including Korean cohorts.

    PubMed

    Jeon, Young-Woo; Cho, Seok-Goo

    2016-05-01

    Only 5th decade ago, chronic lymphocytic leukemia (CLL) was only recognized as disease group of presenting features like peripheral lymphocytosis, organomegaly including of splenomegaly. As understanding of disease biology and molecular diagnostic tools are getting improved gradually, characterization of variation in CLL's clinical courses was facilitated, resulting in better risk stratification and targeted treatments. Consequently multiple new targeted agents have been used in treatment of CLL, it makes improved clinical outcome. Rituximab containing chemoimmunotherapy (combination of rituximab, fludarabine, and cyclophosphamide) have shown better overall response rate and progression-free survival on fit patients' group in front-line setting, result in standard first-line therapeutic option for CLL. Furthermore, after introducing that the B-cell receptor is crucial for the evolution and progression of CLL, emerging treatments targeting highly activated surface antigens and oncogenic signaling pathways have been associated with several successes in recent decades. These include new anti-CD 20 monoclonal antibody (obinutuzumab), the bruton tyrosine kinase inhibitor (ibrutinib), the phosphatidylinositol 3-kinase inhibitor (idelalisib), and B-cell CLL/lymphoma 2 inhibitor (ABT-199 and ABT-263). So, we discuss not only general pathophysiology of CLL, but also rapidly advancing treatment strategies that are being studied or approved for treatment of CLL. PMID:27044858

  20. Psychosis and Hallucinations in FTD with C9ORF72 mutation: A detailed clinical cohort

    PubMed Central

    Kertesz, Andrew; Ang, Lee Cyn; Jesso, Sarah; MacKinley, Julia; Baker, Matt; Brown, Patricia; Shoesmith, Christen; Rademakers, Rosa; Finger, Elizabeth C.

    2014-01-01

    OBJECTIVE To describe in detail the presenting symptoms and clinical course of a cohort of patients with Frontotemporal dementia and the recently described C9ORF72 repeat expansion. BACKGROUND Recent discovery of the C9ORF72 repeat expansion linked to familial frontotemporal dementia and ALS has permitted retrospective evaluation of potential defining clinical characteristics that may distinguish C9ORF72 mutation carriers from other patients with FTD. Prior reports have identified a subset of patients with an increased incidence of psychosis, specifically delusions, though the detailed nature of these symptoms is not yet well described. METHODS We conducted a retrospective chart review of to report the detailed case histories of 7 patients with C9ORF72 mutations from a cohort of 61 patients with FTD. Results Detailed histories available from these patients reveal an increased incidence of psychosis, including visual and auditory hallucinations and delusions compared to sporadic FTD patients in our cohort. CONCLUSIONS This cohort confirms and adds symptom-related details to prior reports of increased incidence of psychotic phenomenon in FTD and ALS patients with C9ORF72 mutations, to enhance future clinical identification and diagnosis of patients presenting with these symptoms. PMID:24077574

  1. Road Traffic and Railway Noise Exposures and Adiposity in Adults: A Cross-Sectional Analysis of the Danish Diet, Cancer, and Health Cohort

    PubMed Central

    Christensen, Jeppe Schultz; Raaschou-Nielsen, Ole; Tjønneland, Anne; Overvad, Kim; Nordsborg, Rikke B.; Ketzel, Matthias; Sørensen, Thorkild IA; Sørensen, Mette

    2015-01-01

    Background Traffic noise has been associated with cardiovascular and metabolic disorders. Potential modes of action are through stress and sleep disturbance, which may lead to endocrine dysregulation and overweight. Objectives We aimed to investigate the relationship between residential traffic and railway noise and adiposity. Methods In this cross-sectional study of 57,053 middle-aged people, height, weight, waist circumference, and bioelectrical impedance were measured at enrollment (1993–1997). Body mass index (BMI), body fat mass index (BFMI), and lean body mass index (LBMI) were calculated. Residential exposure to road and railway traffic noise exposure was calculated using the Nordic prediction method. Associations between traffic noise and anthropometric measures at enrollment were analyzed using general linear models and logistic regression adjusted for demographic and lifestyle factors. Results Linear regression models adjusted for age, sex, and socioeconomic factors showed that 5-year mean road traffic noise exposure preceding enrollment was associated with a 0.35-cm wider waist circumference (95% CI: 0.21, 0.50) and a 0.18-point higher BMI (95% CI: 0.12, 0.23) per 10 dB. Small, significant increases were also found for BFMI and LBMI. All associations followed linear exposure–response relationships. Exposure to railway noise was not linearly associated with adiposity measures. However, exposure > 60 dB was associated with a 0.71-cm wider waist circumference (95% CI: 0.23, 1.19) and a 0.19-point higher BMI (95% CI: 0.0072, 0.37) compared with unexposed participants (0–20 dB). Conclusions The present study finds positive associations between residential exposure to road traffic and railway noise and adiposity. Citation Christensen JS, Raaschou-Nielsen O, Tjønneland A, Overvad K, Nordsborg RB, Ketzel M, Sørensen TI, Sørensen M. 2016. Road traffic and railway noise exposures and adiposity in adults: a cross-sectional analysis of the Danish Diet

  2. The Danish National Lymphoma Registry: Coverage and Data Quality

    PubMed Central

    Arboe, Bente; El-Galaly, Tarec Christoffer; Clausen, Michael Roost; Munksgaard, Peter Svenssen; Stoltenberg, Danny; Nygaard, Mette Kathrine; Klausen, Tobias Wirenfeldt; Christensen, Jacob Haaber; Gørløv, Jette Sønderskov; Brown, Peter de Nully

    2016-01-01

    Background The Danish National Lymphoma Register (LYFO) prospectively includes information on all lymphoma patients newly diagnosed at hematology departments in Denmark. The validity of the clinical information in the LYFO has never been systematically assessed. Aim To test the coverage and data quality of the LYFO. Methods The coverage was tested by merging data of the LYFO with the Danish Cancer Register and the Danish National Patient Register, respectively. The validity of the LYFO was assessed by crosschecking with information from medical records in subgroups of patients. A random sample of 3% (N = 364) was made from all patients in the LYFO. In addition, four subtypes of lymphomas were validated: CNS lymphomas, diffuse large B-cell lymphomas, peripheral T-cell lymphomas, and Hodgkin lymphomas. A total of 1,706 patients from the period 2000–2012 were included. The positive predictive values (PPVs) and completeness of selected variables were calculated for each subgroup and for the entire cohort of patients. Results The comparison of data from the LYFO with the Danish Cancer Register and the Danish National Patient Register revealed a high coverage. In addition, the data quality was good with high PPVs (87% to 100%), and high completeness (92% to 100%). Conclusion The LYFO is a unique, nationwide clinical database characterized by high validity, good coverage and prospective data entry. It represents a valuable resource for future lymphoma research. PMID:27336800

  3. Clinical associations of anti-Smith antibodies in PROFILE: a multi-ethnic lupus cohort.

    PubMed

    Arroyo-Ávila, Mariangelí; Santiago-Casas, Yesenia; McGwin, Gerald; Cantor, Ryan S; Petri, Michelle; Ramsey-Goldman, Rosalind; Reveille, John D; Kimberly, Robert P; Alarcón, Graciela S; Vilá, Luis M; Brown, Elizabeth E

    2015-07-01

    The aim of this study was to determine the association of anti-Sm antibodies with clinical manifestations, comorbidities, and disease damage in a large multi-ethnic SLE cohort. SLE patients (per American College of Rheumatology criteria), age ≥16 years, disease duration ≤10 years at enrollment, and defined ethnicity (African American, Hispanic or Caucasian), from a longitudinal US cohort were studied. Socioeconomic-demographic features, cumulative clinical manifestations, comorbidities, and disease damage (as per the Systemic Lupus International Collaborating Clinics Damage Index [SDI]) were determined. The association of anti-Sm antibodies with clinical features was examined using multivariable logistic regression analyses adjusting for age, gender, ethnicity, disease duration, level of education, health insurance, and smoking. A total of 2322 SLE patients were studied. The mean (standard deviation, SD) age at diagnosis was 34.4 (12.8) years and the mean (SD) disease duration was 9.0 (7.9) years; 2127 (91.6%) were women. Anti-Sm antibodies were present in 579 (24.9%) patients. In the multivariable analysis, anti-Sm antibodies were significantly associated with serositis, renal involvement, psychosis, vasculitis, Raynaud's phenomenon, hemolytic anemia, leukopenia, lymphopenia, and arterial hypertension. No significant association was found for damage accrual. In this cohort of SLE patients, anti-Sm antibodies were associated with several clinical features including serious manifestations such as renal, neurologic, and hematologic disorders as well as vasculitis. PMID:25896533

  4. Using Large Clinical Corpora for Query Expansion in Text-based Cohort Identification

    PubMed Central

    Zhu, Dongqing; Wu, Stephen; Carterette, Ben; Liu, Hongfang

    2014-01-01

    In light of the heightened problems of polysemy, synonymy, and hyponymy in clinical text, we hypothesize that patient cohort identification can be improved by using a large, in-domain clinical corpus for query expansion. We evaluate the utility of four auxiliary collections for the Text REtrieval Conference task of IR-based cohort retrieval, considering the effects of collection size, the inherent difficulty of a query, and the interaction between the collections. Each collection was applied to aid in cohort retrieval from the Pittsburgh NLP Repository by using a mixture of relevance models. Measured by mean average precision, performance using any auxiliary resource (MAP=0.386 and above) is shown to improve over the baseline query likelihood model (MAP=0.373). Considering subsets of the Mayo Clinic collection, we found that after including 2.5 billion term instances, retrieval is not improved by adding more instances. However, adding the Mayo Clinic collection did improve performance significantly over any existing setup, with a system using all four auxiliary collections obtaining the best results (MAP=0.4223). Because optimal results in the mixture of relevance models would require selective sampling of the collections, the common sense approach of “use all available data” is inappropriate. However, we found that it was still beneficial to add the Mayo corpus to any mixture of relevance models. On the task of IR-based cohort identification, query expansion with the Mayo Clinic corpus resulted in consistent and significant improvements. As such, any IR query expansion with access to a large clinical corpus could benefit from the additional resource. Additionally, we have shown that more data is not necessarily better, implying that there is value in collection curation. PMID:24680983

  5. Polymorphisms in the Toll-Like Receptor and the IL-23/IL-17 Pathways Were Associated with Susceptibility to Inflammatory Bowel Disease in a Danish Cohort

    PubMed Central

    Bank, Steffen; Andersen, Paal Skytt; Burisch, Johan; Pedersen, Natalia; Roug, Stine; Galsgaard, Julied; Ydegaard Turino, Stine; Broder Brodersen, Jacob; Rashid, Shaista; Kaiser Rasmussen, Britt; Avlund, Sara; Bastholm Olesen, Thomas; Hoffmann, Hans Jürgen; Andersen Nexø, Bjørn; Sode, Jacob; Vogel, Ulla; Andersen, Vibeke

    2015-01-01

    Background The inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), result from the combined effects of susceptibility genes and environmental factors. Previous studies have shown that polymorphisms in the Toll-like receptor (TLR), the apoptosis, the IL-23/IL-17 and the interferon gamma (IFNG) pathways are associated with risk of both CD and UC. Methods Using a candidate gene approach, 21 functional single nucleotide polymorphisms (SNPs) in 15 genes were assessed in a clinical homogeneous group of severely diseased ethnic Danish patients consisting of 624 patients with CD, 411 patients with UC and 795 controls. The results were analysed using logistic regression. Results The polymorphisms TLR5 (rs5744174) and IL12B (rs6887695) were associated with risk of CD, and TLR1 (rs4833095) and IL18 (rs187238) were associated with risk of both CD and UC (p<0.05). After Bonferroni correction for multiple testing, the homozygous variant genotype of TLR1 743 T>C (rs4833095) was associated with increased risk CD (OR: 3.15, 95% CI: 1.59–6.26, p = 0.02) and CD and UC combined (OR: 2.96, 95% CI: 1.64–5.32, p = 0.005). Conclusion Our results suggest that genetically determined high activity of TLR1 and TLR5 was associated with increased risk of both CD and UC and CD, respectively. This supports that the host microbial composition or environmental factors in the gut are involved in risk of IBD. Furthermore, genetically determined high activity of the IL-23/IL-17 pathway was associated with increased risk of CD and UC. Overall, our results support that genetically determined high inflammatory response was associated with increased risk of both CD and UC. PMID:26698117

  6. Association between tumour necrosis factor-α inhibitors and risk of serious infections in people with inflammatory bowel disease: nationwide Danish cohort study

    PubMed Central

    Pasternak, Björn; Friis-Møller, Nina; Andersson, Mikael; Jess, Tine

    2015-01-01

    Objective To investigate whether people with inflammatory bowel disease treated with tumour necrosis factor-α (TNF-α) inhibitors are at increased risk of serious infections. Design Nationwide register based propensity score matched cohort study. Setting Denmark, 2002-12. Participants The background cohort eligible for matching comprised 52 392 people with inflammatory bowel disease, aged 15 to 75 years, of whom 4300 were treated with TNF-α inhibitors. To limit confounding, a two stage matching method was applied; firstly matching on age, sex, disease duration, and inflammatory bowel disease subtype, and secondly matching on propensity scores (1:1 ratio); this yielded 1543 people treated with TNF-α inhibitors and 1543 untreated to be included in the analyses. Main outcome measures The main outcome was any serious infection, defined as a diagnosis of infection associated with hospital admission. Cox regression was used to estimate hazard ratios for two risk periods (90 and 365 days after the start of TNF-α inhibitor treatment). Hazard ratios of site specific serious infections were obtained solely for the 365 days risk period. Results Within the 90 days risk period, 51 cases of infection were observed in users of TNF-α inhibitors (incidence rate 14/100 person years), compared with 33 cases in non-users (9/100 person years), yielding a hazard ratio of 1.63 (95% confidence interval 1.01 to 2.63). Within the risk period of 365 days, the hazard ratio was 1.27 (0.92 to 1.75). In analyses of site specific infections, the hazard ratio was above 2 for several of the subgroups but only reached statistical significance for skin and soft tissue infections (2.51, 1.23 to 5.12). Conclusions This nationwide propensity score matched cohort study suggests an increased risk of serious infections associated with use of TNF-α inhibitors within the first 90 days of starting treatment and a subsequent decline in risk. This calls for increased clinical awareness of potential

  7. World Health Organization-defined classification of myeloproliferative neoplasms: morphological reproducibility and clinical correlations--the Danish experience.

    PubMed

    Madelung, Ann Brinch; Bondo, Henrik; Stamp, Inger; Loevgreen, Preben; Nielsen, Signe Ledou; Falensteen, Anne; Knudsen, Helle; Ehinger, Mats; Dahl-Sørensen, Rasmus; Mortensen, Nana Brochmann; Svendsen, Kira Dynnes; Lange, Theis; Ralfkiaer, Elisabeth; Nielsen, Karsten; Hasselbalch, Hans Carl; Thiele, Jürgen

    2013-12-01

    We examined inter- and intraobserver reproducibility and concordance between histological diagnosis and independently collected clinical findings in a large series of patients with the major subtypes of myeloproliferative neoplasms (MPNs) and controls. Seven hematopathologists reviewed 272 bone marrow biopsies including 43 controls. Diagnoses were determined according to the 2008 criteria of the World Health Organization (WHO). The participants were blinded to all clinical data except patient age. After initial evaluation all hematopathologists participated in a 3-day meeting with a leading clinician chaired by an expert hematopathologists. In cases with lack of consensus on fiber grading (n = 57), a new evaluation was performed. In cases with discordance on morphological diagnosis (n = 129), an additional nonblinded evaluation taking clinical data into consideration was carried out. For remaining cases with a lack of concordance between morphological diagnosis and clinical diagnosis (n = 33), a similar nonblinded evaluation was performed. Consensus on final histological diagnosis and concordance with clinical diagnosis were determined. Blinded histological evaluation resulted in a 53% consensus rate. After re-evaluation of fiber content, consensus was reached in 60% of cases. Adding clinical data increased the histological consensus to 83%. For cases with a histological consensus, we found a concordance of 71% with the clinician's diagnoses. This is the first study to present a larger cohort of MPN patients mimicking the diagnostic challenges that hematopathologists face in their daily practice. The results support the postulates of the WHO that both morphological and clinical findings are essential for a valid diagnosis PMID:23897670

  8. DEDUCE Clinical Text: An Ontology-based Module to Support Self-Service Clinical Notes Exploration and Cohort Development.

    PubMed

    Roth, Christopher; Rusincovitch, Shelley A; Horvath, Monica M; Brinson, Stephanie; Evans, Steve; Shang, Howard C; Ferranti, Jeffrey M

    2013-01-01

    Large amounts of information, as well as opportunities for informing research, education, and operations, are contained within clinical text such as radiology reports and pathology reports. However, this content is less accessible and harder to leverage than structured, discrete data. We report on an extension to the Duke Enterprise Data Unified Content Explorer (DEDUCE), a self-service query tool developed to provide clinicians and researchers with access to data within the Duke Medicine Enterprise Data Warehouse (EDW). The DEDUCE Clinical Text module supports ontology-based text searching, enhanced filtering capabilities based on document attributes, and integration of clinical text with structured data and cohort development. The module is implemented with open-source tools extensible to other institutions, including a Java-based search engine (Apache Solr) with complementary full-text indexing library (Lucene) employed with a negation engine (NegEx) modified by clinical users to include to local domain-specific negation phrases. PMID:24303270

  9. Biopsychosocial influence on shoulder pain: risk subgroups translated across preclinical and clinical prospective cohorts.

    PubMed

    George, Steven Z; Wallace, Margaret R; Wu, Samuel S; Moser, Michael W; Wright, Thomas W; Farmer, Kevin W; Borsa, Paul A; Parr, Jeffrey J; Greenfield, Warren H; Dai, Yunfeng; Li, Hua; Fillingim, Roger B

    2015-01-01

    Tailored treatment based on individual risk factors is an area with promise to improve options for pain relief. Musculoskeletal pain has a biopsychosocial nature, and multiple factors should be considered when determining risk for chronic pain. This study investigated whether subgroups comprised genetic and psychological factors predicted outcomes in preclinical and clinical models of shoulder pain. Classification and regression tree analysis was performed for an exercise-induced shoulder injury cohort (n = 190) to identify high-risk subgroups, and a surgical pain cohort (n = 150) was used for risk validation. Questionnaires for fear of pain and pain catastrophizing were administered before injury and preoperatively. DNA collected from saliva was genotyped for a priori selected genes involved with pain modulation (COMT and AVPR1A) and inflammation (IL1B and TNF/LTA). Recovery was operationalized as a brief pain inventory rating of 0/10 for current pain intensity and <2/10 for worst pain intensity. Follow-up for the preclinical cohort was in daily increments, whereas follow-up for the clinical cohort was at 3, 6, and 12 months postoperatively. Risk subgroups comprised the COMT high pain sensitivity variant and either pain catastrophizing or fear of pain were predictive of heightened shoulder pain responses in the preclinical model. Further analysis in the clinical model identified the COMT high pain sensitivity variant and pain catastrophizing subgroup as the better predictor. Future studies will determine whether these findings can be replicated in other anatomical regions and whether personalized medicine strategies can be developed for this risk subgroup. PMID:25599310

  10. Identifying Prognostic SNPs in Clinical Cohorts: Complementing Univariate Analyses by Resampling and Multivariable Modeling

    PubMed Central

    Hieke, Stefanie; Benner, Axel; Schlenk, Richard F.; Schumacher, Martin; Bullinger, Lars; Binder, Harald

    2016-01-01

    Clinical cohorts with time-to-event endpoints are increasingly characterized by measurements of a number of single nucleotide polymorphisms that is by a magnitude larger than the number of measurements typically considered at the gene level. At the same time, the size of clinical cohorts often is still limited, calling for novel analysis strategies for identifying potentially prognostic SNPs that can help to better characterize disease processes. We propose such a strategy, drawing on univariate testing ideas from epidemiological case-controls studies on the one hand, and multivariable regression techniques as developed for gene expression data on the other hand. In particular, we focus on stable selection of a small set of SNPs and corresponding genes for subsequent validation. For univariate analysis, a permutation-based approach is proposed to test at the gene level. We use regularized multivariable regression models for considering all SNPs simultaneously and selecting a small set of potentially important prognostic SNPs. Stability is judged according to resampling inclusion frequencies for both the univariate and the multivariable approach. The overall strategy is illustrated with data from a cohort of acute myeloid leukemia patients and explored in a simulation study. The multivariable approach is seen to automatically focus on a smaller set of SNPs compared to the univariate approach, roughly in line with blocks of correlated SNPs. This more targeted extraction of SNPs results in more stable selection at the SNP as well as at the gene level. Thus, the multivariable regression approach with resampling provides a perspective in the proposed analysis strategy for SNP data in clinical cohorts highlighting what can be added by regularized regression techniques compared to univariate analyses. PMID:27159447

  11. Using Semantic Web Technologies for Cohort Identification from Electronic Health Records for Clinical Research

    PubMed Central

    Pathak, Jyotishman; Kiefer, Richard C.; Chute, Christopher G.

    2012-01-01

    The ability to conduct genome-wide association studies (GWAS) has enabled new exploration of how genetic variations contribute to health and disease etiology. One of the key requirements to perform GWAS is the identification of subject cohorts with accurate classification of disease phenotypes. In this work, we study how emerging Semantic Web technologies can be applied in conjunction with clinical data stored in electronic health records (EHRs) to accurately identify subjects with specific diseases for inclusion in cohort studies. In particular, we demonstrate the role of using Resource Description Framework (RDF) for representing EHR data and enabling federated querying and inferencing via standardized Web protocols for identifying subjects with Diabetes Mellitus. Our study highlights the potential of using Web-scale data federation approaches to execute complex queries. PMID:22779040

  12. Using semantic web technologies for cohort identification from electronic health records for clinical research.

    PubMed

    Pathak, Jyotishman; Kiefer, Richard C; Chute, Christopher G

    2012-01-01

    The ability to conduct genome-wide association studies (GWAS) has enabled new exploration of how genetic variations contribute to health and disease etiology. One of the key requirements to perform GWAS is the identification of subject cohorts with accurate classification of disease phenotypes. In this work, we study how emerging Semantic Web technologies can be applied in conjunction with clinical data stored in electronic health records (EHRs) to accurately identify subjects with specific diseases for inclusion in cohort studies. In particular, we demonstrate the role of using Resource Description Framework (RDF) for representing EHR data and enabling federated querying and inferencing via standardized Web protocols for identifying subjects with Diabetes Mellitus. Our study highlights the potential of using Web-scale data federation approaches to execute complex queries. PMID:22779040

  13. Contrasting clinical outcomes in two cohorts of cats naturally infected with feline immunodeficiency virus (FIV)

    PubMed Central

    Bęczkowski, Paweł M.; Litster, Annette; Lin, Tsang Long; Mellor, Dominic J.; Willett, Brian J.; Hosie, Margaret J.

    2015-01-01

    Despite over 25 years of feline immunodeficiency virus (FIV) research, relatively little is known about the longitudinal course of FIV infection following natural infection. In contrast to published reports of experimental infections using lethal strains of the virus, clinical signs of naturally acquired FIV infection can be mild or inapparent, rather than life-threatening. In this prospective, longitudinal controlled study, based in Chicago, IL (n = 17) and Memphis, TN (n = 27), we investigated two cohorts of privately owned, naturally infected cats kept under different housing conditions. Cats in the Chicago cohort (Group 1) were kept in households of ≤2 cats, while the Memphis cohort (Group 2) comprised part of a large multi-cat household of over 60 cats kept indoors only, with unrestricted access to one another. The majority of cats from Group 1 did not display clinical signs consistent with immunodeficiency during the 22-month observation period. In contrast, the outcome of infection in Group 2 was dramatically different; 17/27 (63%) of cats lost a median of 51.3% of their bodyweight (P < 0.0005) and died during the study period, with lymphoma being the most common cause of mortality. Although the decrease in CD4+ T cell count between enrolment and terminal disease was significant (P = 0.0017), the CD4:CD8 ratio at the time of enrolment did not reliably distinguish FIV-positive cats classified as ‘healthy’ and ‘not healthy’ at either cohort. FIV load at enrolment was significantly lower in Group 1 than in Group 2 (P < 0.0001), but there were no significant differences at enrolment between healthy and not healthy cats at either group. In conclusion, the results of this study suggest that management and housing conditions impact on disease progression and survival times of FIV-positive cats. PMID:25595267

  14. Associations of Age, Gender, and Subtypes With ADHD Symptoms and Related Comorbidity in a Danish Sample of Clinically Referred Adults.

    PubMed

    Soendergaard, Helle Moeller; Thomsen, Per Hove; Pedersen, Erik; Pedersen, Pernille; Poulsen, Agnethe Elkjaer; Winther, Lars; Nielsen, Jette Moeskjaer; Henriksen, Anne; Rungoe, Berit; Soegaard, Hans Joergen

    2014-01-10

    Objective: The aim was to examine associations of age and gender with ADHD subtypes and subsequently to examine associations of age, gender, and subtypes with comorbid psychiatric disorders. Method: Odds ratios were calculated and logistic regression performed using information from a clinical sample of 155 ADHD adults referred to a Danish specialized ADHD unit from 2010 to 2011. Results: A majority of men (65%) was found in the sample. Most patients were subtyped ADHD combined (78%), followed by ADHD inattentive (18%), and ADHD hyperactive-impulsive (4%). No significant differences were found in gender and age across subtypes. Current comorbid disorders were found in 57% of the ADHD patients. Significantly more comorbidity was found in the ADHD combined type and in patients ≥25 years. Significantly more men had substance use disorders and significantly more women had personality disorders. Conclusion: When assessing adult ADHD patients' age, gender, subtype, and related comorbid symptom profiles should be taken into account. (J. of Att. Dis. XXXX; XX(X) XX-XX). PMID:24412968

  15. Latent Topic Discovery of Clinical Concepts from Hospital Discharge Summaries of a Heterogeneous Patient Cohort

    PubMed Central

    Lehman, Li-wei; Long, William; Saeed, Mohammed; Mark, Roger

    2016-01-01

    Patients in critical care often exhibit complex disease patterns. A fundamental challenge in clinical research is to identify clinical features that may be characteristic of adverse patient outcomes. In this work, we propose a data-driven approach for phenotype discovery of patients in critical care. We used Hierarchical Dirichlet Process (HDP) as a non-parametric topic modeling technique to automatically discover the latent “topic” structure of diseases, symptoms, and findings documented in hospital discharge summaries. We show that the latent topic structure can be used to reveal phenotypic patterns of diseases and symptoms shared across subgroups of a patient cohort, and may contain prognostic value in stratifying patients’ post hospital discharge mortality risks. Using discharge summaries of a large patient cohort from the MIMIC II database, we evaluate the clinical utility of the discovered topic structure in identifying patients who are at high risk of mortality within one year post hospital discharge. We demonstrate that the learned topic structure has statistically significant associations with mortality post hospital discharge, and may provide valuable insights in defining new feature sets for predicting patient outcomes. PMID:25570320

  16. Latent topic discovery of clinical concepts from hospital discharge summaries of a heterogeneous patient cohort.

    PubMed

    Lehman, Li-Wei; Long, William; Saeed, Mohammed; Mark, Roger

    2014-01-01

    Patients in critical care often exhibit complex disease patterns. A fundamental challenge in clinical research is to identify clinical features that may be characteristic of adverse patient outcomes. In this work, we propose a data-driven approach for phenotype discovery of patients in critical care. We used Hierarchical Dirichlet Process (HDP) as a non-parametric topic modeling technique to automatically discover the latent "topic" structure of diseases, symptoms, and findings documented in hospital discharge summaries. We show that the latent topic structure can be used to reveal phenotypic patterns of diseases and symptoms shared across subgroups of a patient cohort, and may contain prognostic value in stratifying patients' post hospital discharge mortality risks. Using discharge summaries of a large patient cohort from the MIMIC II database, we evaluate the clinical utility of the discovered topic structure in identifying patients who are at high risk of mortality within one year post hospital discharge. We demonstrate that the learned topic structure has statistically significant associations with mortality post hospital discharge, and may provide valuable insights in defining new feature sets for predicting patient outcomes. PMID:25570320

  17. Identifying clinical/translational research cohorts: ascertainment via querying an integrated multi-source database

    PubMed Central

    Hurdle, John F; Haroldsen, Stephen C; Hammer, Andrew; Spigle, Cindy; Fraser, Alison M; Mineau, Geraldine P; Courdy, Samir J

    2013-01-01

    Background Ascertainment of potential subjects has been a longstanding problem in clinical research. Various methods have been proposed, including using data in electronic health records. However, these methods typically suffer from scaling effects—some methods work well for large cohorts; others work for small cohorts only. Objective We propose a method that provides a simple identification of pre-research cohorts and relies on data available in most states in the USA: merged public health data sources. Materials and methods The Utah Population Database Limited query tool allows users to build complex queries that may span several types of health records, such as cancer registries, inpatient hospital discharges, and death certificates; in addition, these can be combined with family history information. The architectural approach incorporates several coding systems for medical information. It provides a front-end graphical user interface and enables researchers to build and run queries and view aggregate results. Multiple strategies have been incorporated to maintain confidentiality. Results This tool was rapidly adopted; since its release, 241 users representing a wide range of disciplines from 17 institutions have signed the user agreement and used the query tool. Three examples are discussed: pregnancy complications co-occurring with cardiovascular disease; spondyloarthritis; and breast cancer. Discussion and conclusions This query tool was designed to provide results as pre-research so that institutional review board approval would not be required. This architecture uses well-described technologies that should be within the reach of most institutions. PMID:23059733

  18. Clinical Characteristics and Outcome of Primary Sjogren’s Syndrome: A Large Asian Indian Cohort

    PubMed Central

    Sandhya, Pulukool; Jeyaseelan, Lakshmanan; Scofield, Robert Hal; Danda, Debashish

    2015-01-01

    Objective : To characterise the clinical features, immunological profile and outcome in a cohort of Asian Indian patients with primary Sjögren's syndrome (SS). Methods : Electronic medical records from a tertiary care teaching hospital in south India were screened for SS between 2004 and 2011. Patients fulfilling American European Consensus group (AECG) 2002 or American College of Rheumatology (ACR) 2012 classification criteria were included. Agglomerative hierarchical cluster analysis to identify patterns of associations between clinical and immunological features was done. Multivariate logistic regression to identify predictors of major systemic involvement was performed. Data on treatment and outcome were retrieved from electronic records. Results : Of 423 patients suspected to have SS, 332 fulfilled inclusion criteria. Only 8.3% of patients complained of sicca symptoms on their own at initial presentation. Younger age of onset, higher female to male ratio, paucity of cryoglobulinemia, Raynaud’s phenomenon and hyperglobulinemia were unique to this cohort. Cluster analysis revealed two subsets: The first cluster comprised of patients having a major systemic illness with high antibody titers and the second comprised of seronegative patients with mild disease. Over a third of SS cases had severe systemic manifestations necessitating treatment with immunosuppressants. In multivariate logistic regression analysis, anti-Ro and anti-La antibody positivity was associated with higher odds for systemic disease features (OR=2.67, P=0.03 and OR=3.25, P=0.003, respectively) whereas chronic pain was associated with lower odds (OR=0.4, p=0.032). Clinical improvement including symptomatic benefit in sicca and musculoskeletal features was noted with immunomodulators in the majority. Conclusion : Our cohort of patients with SS has characteristic clinical features; some of them are in contrast with previous observations reported in European patients. This cohort consisted of

  19. Clinical Significance of Asthma Clusters by Longitudinal Analysis in Korean Asthma Cohort

    PubMed Central

    Kim, Sujeong; Yoon, Sun-young; Kwon, Hyouk-Soo; Chang, Yoon-Seok; Cho, You Sook; Jang, An-Soo; Park, Jung Won; Nahm, Dong-Ho; Yoon, Ho-Joo; Cho, Sang-Heon; Cho, Young-Joo; Choi, ByoungWhui; Moon, Hee-Bom; Kim, Tae-Bum

    2013-01-01

    Background We have previously identified four distinct groups of asthma patients in Korean cohorts using cluster analysis: (A) smoking asthma, (B) severe obstructive asthma, (C) early-onset atopic asthma, and (D) late-onset mild asthma. Methods and Results A longitudinal analysis of each cluster in a Korean adult asthma cohort was performed to investigate the clinical significance of asthma clusters over 12 months. Cluster A showed relatively high asthma control test (ACT) scores but relatively low FEV1 scores, despite a high percentage of systemic corticosteroid use. Cluster B had the lowest mean FEV1, ACT, and the quality of life questionnaire for adult Korean asthmatics (QLQAKA) scores throughout the year, even though the percentage of systemic corticosteroid use was the highest among the four clusters. Cluster C was ranked second in terms of FEV1, with the second lowest percentage of systemic corticosteroid use, and showed a marked improvement in subjective symptoms over time. Cluster D consistently showed the highest FEV1, the lowest systemic corticosteroid use, and had high ACT and QLQAKA scores. Conclusion Our asthma clusters had clinical significance with consistency among clusters over 12 months. These distinctive phenotypes may be useful in classifying asthma in real practice. PMID:24391784

  20. Targeted methylation testing of a patient cohort broadens the epigenetic and clinical description of imprinting disorders.

    PubMed

    Poole, Rebecca L; Docherty, Louise E; Al Sayegh, Abeer; Caliebe, Almuth; Turner, Claire; Baple, Emma; Wakeling, Emma; Harrison, Lucy; Lehmann, Anna; Temple, I Karen; Mackay, Deborah J G

    2013-09-01

    Imprinting disorders are associated with mutations and epimutations affecting imprinted genes, that is those whose expression is restricted by parent of origin. Their diagnosis is challenging for two reasons: firstly, their clinical features, particularly prenatal and postnatal growth disturbance, are heterogeneous and partially overlapping; secondly, their underlying molecular defects include mutation, epimutation, copy number variation, and chromosomal errors, and can be further complicated by somatic mosaicism and multi-locus methylation defects. It is currently unclear to what extent the observed phenotypic heterogeneity reflects the underlying molecular pathophysiology; in particular, the molecular and clinical diversity of multilocus methylation defects remains uncertain. To address these issues we performed comprehensive methylation analysis of imprinted genes in a research cohort of 285 patients with clinical features of imprinting disorders, with or without a positive molecular diagnosis. 20 of 91 patients (22%) with diagnosed epimutations had methylation defects of additional imprinted loci, and the frequency of developmental delay and congenital anomalies was higher among these patients than those with isolated epimutations, indicating that hypomethylation of multiple imprinted loci is associated with increased diversity of clinical presentation. Among 194 patients with clinical features of an imprinting disorder but no molecular diagnosis, we found 15 (8%) with methylation anomalies, including missed and unexpected molecular diagnoses. These observations broaden the phenotypic and epigenetic definitions of imprinting disorders, and show the importance of comprehensive molecular testing for patient diagnosis and management. PMID:23913548

  1. Clinical orofacial characteristics associated with risk of first-onset TMD: the OPPERA prospective cohort study

    PubMed Central

    Ohrbach, Richard; Bair, Eric; Fillingim, Roger B.; Gonzalez, Yoly; Gordon, Sharon M.; Lim, Pei-Feng; Ribeiro-Dasilva, Margarete; Diatchenko, Luda; Dubner, Ron; Greenspan, Joel D.; Knott, Charles; Maixner, William; Smith, Shad; Slade, Gary

    2013-01-01

    Case-control studies have documented clinical manifestations of chronic temporomandibular disorders (TMD), whereas clinical predictors of TMD development are largely unknown. We evaluated 41 clinical orofacial characteristics thought to predict first-onset TMD in a prospective cohort study of U.S. adults aged 18-44 years. During the median 2.8-year follow-up period, 2,737 people completed quarterly screening questionnaires. Those reporting symptoms were examined and 260 people were identified with first-onset TMD. Univariate and multivariate Cox regression models quantified associations between baseline clinical orofacial measures and TMD incidence. Significant predictors from baseline self-report instruments included oral parafunctions, prior facial pain and its life-impact, TMJ noises and jaw locking, and non-specific orofacial symptoms. Significant predictors from the baseline clinical examination were pain on jaw opening and pain from palpation of masticatory, neck, and body muscles. Examiner assessments of TMJ noise and tooth wear facets did not predict incidence. In multivariate analysis, non-specific orofacial symptoms, pain from jaw opening and oral parafunctions predicted TMD incidence. The results indicate that only a few orofacial examination findings influenced TMD incidence, and only to a modest degree. More pronounced influences were found for self-reported symptoms, particularly those that appeared to reflect alterations to systems beyond the masticatory tissues. PMID:24275222

  2. UCP3 polymorphisms, hand grip performance and survival at old age: Association analysis in two Danish middle aged and elderly cohorts

    PubMed Central

    Dato, Serena; Soerensen, Mette; Montesanto, Alberto; Lagani, Vincenzo; Passarino, Giuseppe; Christensen, Kaare; Christiansen, Lene

    2013-01-01

    An efficient uncoupling process is generally considered to have a protective effect on the aging muscle by slowing down its age-related decay. Genetic polymorphisms in the Uncoupling Protein 3 (UCP3) gene, whose product is mainly expressed in skeletal muscle, were suggested to be associated with hand grip (HG) performances in elderly populations. Considering the population specificity of the quality of aging, we aimed to add further support to this evidence by analyzing the association between four SNPs in the UCP3 gene and relative haplotypes in two large cohorts of middle aged (N = 708) and oldest old Danes (N = 908). We found that the variability at rs1685354 and rs11235972 was associated with HG levels both at single and haplotypic level in both cohorts. Furthermore, taking advantage of large cohort and period survival data of the oldest cohort, we tested the association of each SNP with survival at 10 years from the baseline visit. Interestingly, we found that allele A at rs11235972, associated in this cohort with lowest HG scores, influences also the survival patterns, with people carrying this allele showing higher mortality rates. On the whole, our work supports the role of UCP3 gene in functional status and survival at old age. PMID:22743239

  3. The clinical outcomes of chronic hepatitis C in South Korea: A prospective, multicenter cohort study.

    PubMed

    Ok, Kyeong Sam; Jeong, Sook-Hyang; Jang, Eun Sun; Kim, Young Seok; Lee, Youn Jae; Kim, In Hee; Cho, Sung Bum; Bae, Si Hyun; Lee, Han Chu

    2016-08-01

    This prospective cohort study aimed to elucidate the clinical outcome and its related factors of chronic hepatitis C in a hepatitis B-dominant Asian region.From January 2007 to October 2012, 382 patients with chronic hepatitis C without liver cirrhosis were prospectively enrolled at 6 university hospitals, and regularly followed until Apr 2014 to identify the development of liver cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC), and overall survival.During the median follow-up of 39.0 months (range 18.0-81.0 months), liver cirrhosis, hepatic decompensation, and HCC developed in 42 patients (11.0%), 4 patients (1.0%), and 12 patients (3.1%), respectively. The cumulative probability of development of cirrhosis at 3 years and at 5 years was 9.6% and 16.7%, respectively. That of HCC at 3 and 5 years was 1.6% and 4.5%, respectively. The 3-year and 5-year overall survival rate was 99.7% and 96.0%, respectively. Pegylated interferon-based antiviral therapy was undertaken in 237 patients (62.0%) with a sustained virologic response (SVR) rate of 74.3%. The factors related to the overall clinical outcomes were age ≥55 years (HR 2.924, P = 0.016), platelet counts <150  × 10/L (HR 3.195, P = 0.007), and the achievement of SVR (HR 0.254, P = 0.002).The clinical outcomes of this Korean chronic hepatitis C cohort were modest with minimal mortality, but significant disease progression occurred in the patients with old age, low platelet, and non-SVR after interferon-based antiviral treatment or no treatment, suggesting priority for direct acting antiviral therapy. PMID:27583874

  4. Polysomnographic Findings and Clinical Correlates in Huntington Disease: A Cross-Sectional Cohort Study

    PubMed Central

    Piano, Carla; Losurdo, Anna; Della Marca, Giacomo; Solito, Marcella; Calandra-Buonaura, Giovanna; Provini, Federica; Bentivoglio, Anna Rita; Cortelli, Pietro

    2015-01-01

    Study Objectives: To evaluate the sleep pattern and the motor activity during sleep in a cohort of patients affected by Huntington disease (HD). Design: Cross-sectional cohort study. Setting: Sleep laboratory. Patients: Thirty HD patients, 16 women and 14 men (mean age 57.3 ± 12.2 y); 30 matched healthy controls (mean age 56.5 ± 11.8 y). Interventions: Subjective sleep evaluation: Epworth Sleepiness Scale (ESS); Berlin's Questionnaire, interview for restless legs syndrome (RLS), questionnaire for REM sleep behavior disorder (RBD). Clinical evaluation: disease duration, clinical severity (unified Huntington disease motor rating scale [UHDMRS]), genetic tests. Laboratory-based full-night attended video-polysomnography (V-PSG). Measurements and Results: The duration of the disease was 9.4 ± 4.4 y, UHMDRS score was 55.5 ± 23.4, CAG repeats were 44.3 ± 4.1. Body mass index was 21.9 ± 4.0 kg/m2. No patients or caregivers reported poor sleep quality. Two patients reported symptoms of RLS. Eight patients had an ESS score ≥ 9. Eight patients had high risk of obstructive sleep apnea. At the RBD questionnaire, two patients had a pathological score. HD patients, compared to controls, showed shorter sleep, reduced sleep efficiency index, and increased arousals and awakenings. Four patients presented with sleep disordered breathing (SDB). Periodic limb movements (PLMs) during wake and sleep were observed in all patients. No episode of RBD was observed in the V-PSG recordings, and no patients showed rapid eye movement (REM) sleep without atonia. The disease duration correlated with ESS score (P < 0.02). UHMDRS correlated positively with the ESS score (P < 0.005), and negatively with the percentage of REM sleep. Conclusions: Patients with Huntington disease showed a severe sleep disruption and a high prevalence of periodic limb movements, but no evidence of sleep disordered breathing or REM sleep behavior disorder. Citation: Piano C, Losurdo A, Della Marca G, Solito M

  5. No Association between HMOX1 and Risk of Colorectal Cancer and No Interaction with Diet and Lifestyle Factors in a Prospective Danish Case-Cohort Study

    PubMed Central

    Andersen, Vibeke; Kopp, Tine Iskov; Tjønneland, Anne; Vogel, Ulla

    2015-01-01

    Red meat is a risk factor for colorectal cancer (CRC). We wanted to evaluate whether a functional polymorphism in the HMOX1 gene encoding heme oxygenase modifies risk of CRC or interacts with diet or lifestyle factors because this would identify heme or heme iron as a risk factor of CRC. The HMOX1 A-413T (rs2071746) was assessed in relation to risk of colorectal cancer (CRC) and interactions with diet (red meat, fish, fiber, cereals, fruit and vegetables) and lifestyle (use of non-steroidal anti-inflammatory drug and smoking status) were assessed in a case-cohort study of 928 CRC cases and a comparison group of 1726 randomly selected participants from a prospective study of 57,053 persons. No association between HMOX1 A-413T and CRC risk was found (TT vs. AA + TA; IRR = 1.15, 95% CI: 0.98–1.36, p = 0.10 for the adjusted estimate). No interactions were found between diet or lifestyle and HMOX1 A-413T. HMOX1 A-413T was not associated with CRC risk and no interactions with diet or lifestyle were identified in this large, prospective cohort with high meat intake. The results reproduced the previous findings from the same cohort and did not support a link between heme or heme iron and colorectal cancer. These results should be sought and replicated in other well-characterized cohorts with high meat intake. PMID:25574604

  6. Clinical determinants of Lyme borreliosis, babesiosis, bartonellosis, anaplasmosis, and ehrlichiosis in an Australian cohort

    PubMed Central

    Mayne, Peter J

    2015-01-01

    Background Borrelia burgdorferi is the causative agent of Lyme borreliosis. This spirochete, along with Babesia, Bartonella, Anaplasma, Ehrlichia, and the Rickettsia spp. are recognized tick-borne pathogens. In this study, the clinical manifestation of these zoonoses in Australia is described. Methods The clinical presentation of 500 patients over the course of 5 years was examined. Evidence of multisystem disease and cranial nerve neuropathy was sought. Supportive laboratory evidence of infection was examined. Results Patients from every state of Australia presented with a wide range of symptoms of disease covering multiple systems and a large range of time intervals from onset. Among these patients, 296 (59%) were considered to have a clinical diagnosis of Lyme borreliosis and 273 (54% of the 500) tested positive for the disease, the latter not being a subset of the former. In total, 450 (90%) had either clinical evidence for or laboratory proof of borrelial infection, and the great majority of cases featured neurological symptoms involving the cranial nerves, thus mimicking features of the disease found in Europe and Asia, as distinct from North America (where extracutaneous disease is principally an oligoarticular arthritis). Only 83 patients (17%; number [n]=492) reported never leaving Australia. Of the 500 patients, 317 (63%) had clinical or laboratory-supported evidence of coinfection with Babesia or Bartonella spp. Infection with A. phagocytophilum was detected in three individuals, and Ehrlichia chaffeensis was detected in one individual who had never traveled outside Australia. In the cohort, 30 (11%; n=279) had positive rickettsial serology. Conclusion The study suggests that there is a considerable presence of borreliosis in Australia, and a highly significant burden of coinfections accompanying borreliosis transmission. The concept sometimes advanced of a “Lyme-like illness” on the continent needs to be re-examined as the clinical interplay between

  7. Rare Causes of Primary Adrenal Insufficiency: Genetic and Clinical Characterization of a Large Nationwide Cohort

    PubMed Central

    Buonocore, Federica; Saka, Nurcin; Ozbek, Mehmet Nuri; Aycan, Zehra; Bereket, Abdullah; Bas, Firdevs; Darcan, Sukran; Bideci, Aysun; Guven, Ayla; Demir, Korcan; Akinci, Aysehan; Buyukinan, Muammer; Aydin, Banu Kucukemre; Turan, Serap; Agladioglu, Sebahat Yilmaz; Atay, Zeynep; Abali, Zehra Yavas; Tarim, Omer; Catli, Gonul; Yuksel, Bilgin; Akcay, Teoman; Yildiz, Metin; Ozen, Samim; Doger, Esra; Demirbilek, Huseyin; Ucar, Ahmet; Isik, Emregul; Ozhan, Bayram; Bolu, Semih; Ozgen, Ilker Tolga; Suntharalingham, Jenifer P.; Achermann, John C.

    2016-01-01

    Context: Primary adrenal insufficiency (PAI) is a life-threatening condition that is often due to monogenic causes in children. Although congenital adrenal hyperplasia occurs commonly, several other important molecular causes have been reported, often with overlapping clinical and biochemical features. The relative prevalence of these conditions is not known, but making a specific diagnosis can have important implications for management. Objective: The objective of the study was to investigate the clinical and molecular genetic characteristics of a nationwide cohort of children with PAI of unknown etiology. Design: A structured questionnaire was used to evaluate clinical, biochemical, and imaging data. Genetic analysis was performed using Haloplex capture and next-generation sequencing. Patients with congenital adrenal hyperplasia, adrenoleukodystrophy, autoimmune adrenal insufficiency, or obvious syndromic PAI were excluded. Setting: The study was conducted in 19 tertiary pediatric endocrinology clinics. Patients: Ninety-five children (48 females, aged 0–18 y, eight familial) with PAI of unknown etiology participated in the study. Results: A genetic diagnosis was obtained in 77 patients (81%). The range of etiologies was as follows: MC2R (n = 25), NR0B1 (n = 12), STAR (n = 11), CYP11A1 (n = 9), MRAP (n = 9), NNT (n = 7), ABCD1 (n = 2), NR5A1 (n = 1), and AAAS (n = 1). Recurrent mutations occurred in several genes, such as c.560delT in MC2R, p.R451W in CYP11A1, and c.IVS3ds+1delG in MRAP. Several important clinical and molecular insights emerged. Conclusion: This is the largest nationwide study of the molecular genetics of childhood PAI undertaken. Achieving a molecular diagnosis in more than 80% of children has important translational impact for counseling families, presymptomatic diagnosis, personalized treatment (eg, mineralocorticoid replacement), predicting comorbidities (eg, neurological, puberty/fertility), and targeting clinical genetic testing in the

  8. Safety of bevacizumab in clinical practice for recurrent ovarian cancer: A retrospective cohort study

    PubMed Central

    SELLE, FRÉDÉRIC; EMILE, GEORGE; PAUTIER, PATRICIA; ASMANE, IRÈNE; SOARES, DANIELE G.; KHALIL, AHMED; ALEXANDRE, JEROME; LHOMMÉ, CATHERINE; RAY-COQUARD, ISABELLE; LOTZ, JEAN-PIERRE; GOLDWASSER, FRANÇOIS; TAZI, YOUSSEF; HEUDEL, PIERRE; PUJADE-LAURAINE, ERIC; GOUY, SÉBASTIEN; TREDAN, OLIVIER; BARBAZA, MARIE O.; ADY-VAGO, NORA; DUBOT, CORALINE

    2016-01-01

    The poor outcome of patients with recurrent ovarian cancer constitutes a continuous challenge for decision-making in clinical practice. In this setting, molecular targets have recently been identified, and novel compounds are now available. Bevacizumab has been introduced for the treatment of patients with ovarian cancer and is, to date, the most extensively investigated targeted therapy in this setting. However, potential toxicities are associated with the use of this monoclonal antibody. These toxicities have been reported in clinical trials, and can also be observed outside of trials. As limited data is currently available regarding the safety of bevacizumab treatment in daily clinical practice, the current retrospective study was designed to evaluate this. Data from 156 patients with recurrent ovarian cancer who had received bevacizumab treatment between January 2006 and June 2009 were retrospectively identified from the institutional records of five French centers. In contrast to clinical trials, the patients in the present study were not selected and had a heterogeneous profile according to their prior medical history, lines of treatment prior to bevacizumab introduction and number of relapses. The results first confirm the effect of heavy pretreatment on the occurrence of serious and fatal adverse events in clinical practice, as previously reported for clinical trials and for other retrospective cohort studies. Importantly, the data also demonstrates, for the first time, that medical history of hypertension is an independent predictive risk factor for the development of high-grade hypertension during bevacizumab treatment. These results thus suggest that treating physicians must consider all risk factors for managing bevacizumab toxicity prior to its introduction. Such risk factors include the time of bevacizumab introduction, a patient's history of hypertension and a low incidence of pre-existing obstructive disease. PMID:26998090

  9. A clinical and radiological profile of neuromyelitis optica and spectrum disorders in an Indian cohort

    PubMed Central

    Barhate, Kavita Sohan; Ganeshan, Malti; Singhal, Bhim Sen

    2014-01-01

    Background: There is insufficient data on the clinical and radiological features of neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD) from India. Objective: The objective of the following study is to examine the clinico-radiological features of NMO and NMOSD in an Indian cohort. Materials and Methods: This retrospective study included 44 consecutive patients who (1) satisfied the 2006 Wingerchuk criteria for NMO (16 seropositive and 7 seronegative); or (2) had isolated or recurrent optic neuritis (ON) with seropositivity (n = 4); or (3) had isolated or recurrent myelitis with seropositivity (n = 17). Results: The female:male ratio was 7.8:1 with median age of onset 26.5 (range 8-72). Annualized relapse rate (ARR) was comparable across all groups (F [3, 40] = 0.938 and P = 0.431). Various presentations other than ON and myelitis were noted. All 40 patients with myelitis had spinal cord lesions involving ≥3 vertebral segments during the course of the disease. Cervicomedullary involvement was seen in 32.5% (13/40) patients. Brain magnetic resonance imaging was available for 40 patients; eight of these (20%) had brain lesions in locations described in multiple sclerosis (MS), 27.5% (11/40) had lesions at sites unusual for MS and 52.5% (21/40) had normal brain imaging. Conclusion: NMO and NMOSD patients in this cohort have comparable ARR regardless of clinical presentation, supporting the emerging trend of treating all patients with immunotherapeutic agents at an early stage. Varied presentations seen in NMO and NMOSD highlight the need for a high index of suspicion for NMO in demyelinating episodes not classical for MS. PMID:24753665

  10. The High Prevalence of Diabetes in a Large Cohort of Patients Drawn From Safety Net Clinics

    PubMed Central

    McBurnie, MaryAnn; Paul, Ludmilla; Potter, Jennifer E.; McCann, Sheila; Mayer, Kenneth; Melgar, Gerardo; D’Amato, Sele; DeVoe, Jennifer E.

    2016-01-01

    Introduction Underserved populations have been overlooked or underrepresented in research based on data from diabetes registries. We estimated diabetes prevalence using a cohort developed from the electronic health records of 3 networks of safety net clinics that provide care to underserved populations. Methods ADVANCE (Accelerating Data Value Across a National Community Health Center Network) is a partnership of the OCHIN Community Health Information Network (OCHIN), the Health Choice Network (HCN), and the Fenway Health Institute (FHI), representing 97 federally qualified health centers (FQHCs) and 744 clinic sites in 22 US states. Among 952,316 adults with a body mass index (BMI) measurement and at least 2 outpatient visits in 2012 to 2014, we calculated diabetes prevalence using outpatient diagnoses, diagnostic laboratory results, or dispenses of anti-hyperglycemic agents no more than 730 days apart. We calculated prevalence by age, sex, race, Hispanic ethnicity, and BMI class. Results The crude prevalence of diabetes was 14.4%. Men had a higher prevalence than women (16.5% vs 13.2%); diabetes prevalence increased across age categories. White patients had the lowest prevalence (11.4%) and Hawaiian/Pacific Islanders, the highest prevalence (21.9%), with prevalence ranging from 15.2% to 16.5% for other race/ethnicities. The association between BMI class and diabetes prevalence was similar across all racial/ethnic groups. Conclusion The ADVANCE diabetes cohort offers an opportunity to conduct epidemiologic and comparative effectiveness research on underserved and underrepresented individuals, who have a higher prevalence of diabetes than the general US population. PMID:27309415

  11. Clinical and Epidemiological Factors Associated with Mortality in Parkinson's Disease in a Brazilian Cohort

    PubMed Central

    Fernandes, Gustavo Costa; Socal, Mariana Peixoto; Schuh, Artur Francisco Schumacher; Rieder, Carlos R. M.

    2015-01-01

    Background. Prognosis of PD is variable. Most studies show higher mortality rates in PD patients compared to the general population. Clinical and epidemiologic factors predicting mortality are poorly understood. Methods. Clinical and epidemiologic features including patient history and physical, functional, and cognitive scores were collected from a hospital-based cohort of PD patients using standardized protocols and clinical scales. Data on comorbidities and mortality were collected on follow-up. Results. During a mean follow-up of 4.71 years (range 1–10), 43 (20.9%) of the 206 patients died. Those who died had higher mean age at disease onset than those still alive at the last follow-up (67.7 years versus 56.3 years; p < 0.01). In the univariate analysis, age at baseline was associated with decreased survival. In the adjusted Cox proportional hazards model, age at disease onset and race/ethnicity were predictors of mortality. Conclusions. Late age at disease onset and advanced chronological age are associated with decreased survival. Comorbidities and PD characteristics were not associated with decreased survival in our sample. Race/ethnicity was found in our study to be associated with increased hazard of mortality. Our findings indicate the importance of studying survival among different populations of PD patients. PMID:26819798

  12. Clinical and Epidemiological Factors Associated with Mortality in Parkinson's Disease in a Brazilian Cohort.

    PubMed

    Fernandes, Gustavo Costa; Socal, Mariana Peixoto; Schuh, Artur Francisco Schumacher; Rieder, Carlos R M

    2015-01-01

    Background. Prognosis of PD is variable. Most studies show higher mortality rates in PD patients compared to the general population. Clinical and epidemiologic factors predicting mortality are poorly understood. Methods. Clinical and epidemiologic features including patient history and physical, functional, and cognitive scores were collected from a hospital-based cohort of PD patients using standardized protocols and clinical scales. Data on comorbidities and mortality were collected on follow-up. Results. During a mean follow-up of 4.71 years (range 1-10), 43 (20.9%) of the 206 patients died. Those who died had higher mean age at disease onset than those still alive at the last follow-up (67.7 years versus 56.3 years; p < 0.01). In the univariate analysis, age at baseline was associated with decreased survival. In the adjusted Cox proportional hazards model, age at disease onset and race/ethnicity were predictors of mortality. Conclusions. Late age at disease onset and advanced chronological age are associated with decreased survival. Comorbidities and PD characteristics were not associated with decreased survival in our sample. Race/ethnicity was found in our study to be associated with increased hazard of mortality. Our findings indicate the importance of studying survival among different populations of PD patients. PMID:26819798

  13. RISK OF HEMOPTYSIS IN CYSTIC FIBROSIS CLINICAL TRIALS: A RETROSPECTIVE COHORT STUDY

    PubMed Central

    Mayer-Hamblett, N.; Kloster, M.; Bilton, D.; Flume, P. A.

    2015-01-01

    Background Cystic fibrosis (CF) is characterized by airways infection and inflammation resulting in respiratory complications including hemoptysis. The objectives of this study were to characterize risk of hemoptysis attributable to the underlying disease and in the presence of standard of care therapy. Methods This retrospective cohort study estimated hemoptysis rates overall and by relevant risk factors utilizing adverse event data from longitudinal prospective CF clinical trials. Results Of the 1008 participants, 73% were ≤18 years old; of 929 with available spirometry, 27% had an FEV1 < 70% predicted. During the average 8.2 months of follow-up, 8% experienced ≥1 hemoptysis events (95% CI: 6%, 10%). Of the 125 events, 76% were mild in severity and only 9% were serious. Hemoptysis rates were greater among adults than children, those with FEV1 < 70% predicted, and participants infected with P. aeruginosa but not with S. aureus. Conclusions Hemoptysis is a common adverse event among CF clinical trial participants, and particularly in adults with more severe lung disease. These results can be used to predict event occurrence in future clinical trials. PMID:25725985

  14. Diabetes Is Associated with Worse Clinical Presentation in Tuberculosis Patients from Brazil: A Retrospective Cohort Study

    PubMed Central

    Hickson, Lucas S.; Daltro, Carla; Castro, Simone; Kornfeld, Hardy; Netto, Eduardo M.; Andrade, Bruno B.

    2016-01-01

    Background The rising prevalence of diabetes mellitus (DM) worldwide, especially in developing countries, and the persistence of tuberculosis (TB) as a major public health issue in these same regions, emphasize the importance of investigating this association. Here, we compared the clinical profile and disease outcomes of TB patients with or without coincident DM in a TB reference center in Brazil. Methods We performed a retrospective analysis of a TB patient cohort (treatment naïve) of 408 individuals recruited at a TB primary care center in Brazil between 2004 and 2010. Data on diagnosis of TB and DM were used to define the groups. The study groups were compared with regard to TB disease presentation at diagnosis as well as to clinical outcomes such as cure and mortality rates upon anti-tuberculosis therapy (ATT) initiation. A composite score utilizing clinical, radiological and microbiological parameters was used to compare TB severity between the groups. Results DM patients were older than non-diabetic TB patients. In addition, diabetic individuals more frequently presented with cough, night sweats, hemoptysis and malaise than those without DM. The overall pattern of lung lesions assessed by chest radiographic examination was similar between the groups. Compared to non-diabetic patients, those with TB-diabetes exhibited positive acid-fast bacilli in sputum samples more frequently at diagnosis and at 30 days after ATT initiation. Notably, higher values of the TB severity score were significantly associated with TB-diabetes comorbidity after adjustment for confounding factors. Moreover, during ATT, diabetic patients required more frequent transfers to TB reference hospitals for complex clinical management. Nevertheless, overall mortality and cure rates were indistinguishable between the study groups. Conclusions These findings reinforce the idea that diabetes negatively impacts pulmonary TB severity. Our study argues for the systematic screening for DM in TB

  15. Can Psychopathology at Age 7 Be Predicted from Clinical Observation at One Year? Evidence from the ALSPAC Cohort

    ERIC Educational Resources Information Center

    Allely, C. S.; Doolin, O.; Gillberg, C.; Gillberg, I. C.; Puckering, C.; Smillie, M.; McConnachie, A.; Heron, J.; Golding, J.; Wilson, P.

    2012-01-01

    One of the challenges of developmental psychopathology is to determine whether identifiable pathways to developmental disorders exist in the first months or years of life. Early identification of such disorders poses a similar challenge for clinical services. Using data from a large contemporary birth cohort, we examined whether psychopathology at…

  16. Cost and clinical consequences of smoking cessation in outpatients after cardiovascular disease: a retrospective cohort study

    PubMed Central

    Sicras-Mainar, Antoni; Díaz-Cerezo, Silvia; de Burgoa, Verónica Sanz; Navarro-Artieda, Ruth

    2013-01-01

    This cohort retrospective study explored the cost and clinical consequences of smoking cessation in outpatients after cardiovascular events (CVEs), in Spain. A total of 2,540 patients (68.1 years; 60.7% male; 8.4% smokers, 52.9% ex-smokers, and 38.7% never smokers) fulfilling the selection criteria and followed up throughout a period of 36 months after the event were considered eligible for analysis. Total costs were higher among current smokers in comparison with ex-smokers and never smokers (€7,981 versus [vs] €7,322 and €5,619, respectively) (P < 0.001). Both health care costs (€6,273 vs €5,673 and €4,823, respectively) (P < 001) and loss of productivity at work costs (€1,708 vs €1,650 and €796, respectively) (P < 001) accounted for such differences. There was also a difference in CVE recurrence rates (18.6% vs 16.5% and 9.6%, respectively) (P < 01). Smoking cessation in CVE outpatients was associated with lower cost and risk of CVE recurrence compared with smokers, and their health status was similar to that of never smokers, in routine clinical practice in Spain. PMID:23983479

  17. Clinical Attack Rate of Chikungunya in a Cohort of Nicaraguan Children.

    PubMed

    Balmaseda, Angel; Gordon, Aubree; Gresh, Lionel; Ojeda, Sergio; Saborio, Saira; Tellez, Yolanda; Sanchez, Nery; Kuan, Guillermina; Harris, Eva

    2016-02-01

    Chikungunya virus (CHIKV) was recently introduced into the Americas. In Nicaragua, the first endogenous transmission of CHIKV was recognized in September 2014. We used an ongoing dengue cohort study of children aged 2-14 years in Managua, Nicaragua, to document the attack rate of symptomatic chikungunya in a presumably naive population. From September 2014 through March 2015, the overall clinical attack rate of laboratory-confirmed CHIKV infection was 2.9% (95% confidence interval [CI]: 2.3%, 3.4%). The attack rate was greater in children ≥ 8 years of age (4.1%; 95% CI: 3.2%, 5.1%) than in those < 8 years of age (1.5%; 95% CI: 0.9%, 2.1%). The mean age of CHIKV cases presenting with typical chikungunya symptoms was 9.8 years, compared with 7.8 years for cases presenting with undifferentiated fever (P = 0.04). Our data suggest that the clinical attack rate in children may underestimate the true burden of disease as some children, especially young children, may experience more atypical symptoms (e.g., undifferentiated fever). PMID:26643531

  18. Multiple Treatments of Pediatric Constraint-Induced Movement Therapy (pCIMT): A Clinical Cohort Study.

    PubMed

    DeLuca, Stephanie C; Ramey, Sharon Landesman; Trucks, Mary Rebekah; Wallace, Dorian Ainsworth

    2015-01-01

    Pediatric constraint-induced movement therapy (pCIMT) is one of the most efficacious treatments for children with cerebral palsy (CP). Distinctive components of pCIMT include constraint of the less impaired upper extremity (UE), high-intensity therapy for the more impaired UE (≥ 3 hr/day, many days per week, for multiple weeks), use of shaping techniques combined with repetitive task practice, and bimanual transfer. A critical issue is whether multiple treatments of pCIMT produce additional benefit. In a clinical cohort (mean age = 31 mo) of 28 children with asymmetrical CP whose parents sought multiple pCIMT treatments, the children gained a mean of 13.2 (standard deviation [SD] = 4.2) new functional skills after Treatment 1; Treatment 2 produced a mean of 7.3 (SD = 4.7) new skills; and Treatment 3, 6.5 (SD = 4.2). These findings support the conclusion that multiple pCIMT treatments can produce clinically important functional gains for children with hemiparetic CP. PMID:26565094

  19. Multiple Treatments of Pediatric Constraint-Induced Movement Therapy (pCIMT): A Clinical Cohort Study

    PubMed Central

    Ramey, Sharon Landesman; Trucks, Mary Rebekah; Wallace, Dorian Ainsworth

    2015-01-01

    Pediatric constraint-induced movement therapy (pCIMT) is one of the most efficacious treatments for children with cerebral palsy (CP). Distinctive components of pCIMT include constraint of the less impaired upper extremity (UE), high-intensity therapy for the more impaired UE (≥3 hr/day, many days per week, for multiple weeks), use of shaping techniques combined with repetitive task practice, and bimanual transfer. A critical issue is whether multiple treatments of pCIMT produce additional benefit. In a clinical cohort (mean age = 31 mo) of 28 children with asymmetrical CP whose parents sought multiple pCIMT treatments, the children gained a mean of 13.2 (standard deviation [SD] = 4.2) new functional skills after Treatment 1; Treatment 2 produced a mean of 7.3 (SD = 4.7) new skills; and Treatment 3, 6.5 (SD = 4.2). These findings support the conclusion that multiple pCIMT treatments can produce clinically important functional gains for children with hemiparetic CP. PMID:26565094

  20. A Reverse Dipping Pattern Predicts Cardiovascular Mortality In a Clinical Cohort

    PubMed Central

    Kim, Bae Keun; Kim, Yu-Mi; Lee, Youngu; Lim, Young-Hyo

    2013-01-01

    An abnormal dipping pattern in ambulatory blood pressure monitoring (ABPM) is a cardiovascular (CV) risk factor. However, its impact on CV mortality has not been investigated sufficiently in clinical practice to be considered a standard parameter. We assessed the association between abnormal dipping patterns and increased CV mortality in a tertiary hospital in Korea. Our retrospective cohort study included 401 patients who underwent ABPM between 1994 and 1996 in Hanyang University Hospital, Seoul, Korea. The patients were classified as risers (<0% drop in systolic BP; n=107), and others included dippers and non-dippers (≥0% drop, n=294). The follow-up period was 120 months. The frequency of CV mortality was 14.0% in risers and 5.8% in others. A Cox regression analysis found a significant association between dipping pattern and CV mortality, after adjusting for age, gender, body mass index, hypertension, diabetes mellitus, smoking and hypercholesterolemia. Risers were at greater risk of CV death than others (RR, 3.02, P=0.022), but there was no difference in event rates between dippers and non-dippers. The reverse dipping pattern may be more frequent in clinical settings than in the population at large, and it is strongly associated with increased risk of CV mortality in Korea. PMID:24133351

  1. Psychosocial work environment and incidence of severe depressive symptoms: prospective findings from a 5-year follow-up of the Danish work environment cohort study.

    PubMed

    Rugulies, Reiner; Bültmann, Ute; Aust, Birgit; Burr, Hermann

    2006-05-15

    The authors analyzed the impact of psychosocial work characteristics on the incidence of severe depressive symptoms among 4,133 (49% women) employees from a representative sample of the Danish workforce between 1995 and 2000. Psychosocial work characteristics at baseline included quantitative demands, influence at work, possibilities for development, social support from supervisors and coworkers, and job insecurity. Severe depressive symptoms were measured with the five-item Mental Health Inventory of the 36-item Short-Form Health Survey, with a cutoff point of 52. Women with low influence at work (relative risk (RR) = 2.17, 95% confidence interval (CI): 1.23, 3.82) and low supervisor support (RR = 2.03, 95% CI: 1.20, 3.43) were at increased risk for severe depressive symptoms after exclusion of cases at baseline and adjustment for sociodemographic factors, baseline depression score, and health behaviors. Further adjustments for socioeconomic position did not change the result substantially. Additional analyses showed that a one-standard deviation increase on the influence scale resulted in a 27% decreased risk of severe depressive symptoms. Among men, job insecurity predicted severe depressive symptoms (RR = 2.04, 95% CI: 1.02, 4.07). The findings indicate that the work environment influences the risk of developing severe depressive symptoms and that different factors play a role for men and women. PMID:16571741

  2. Clinical, Electroencephalographic, and Neuroradiological Outcome Predictors in Acute Nonhypoxic Encephalopathy: A Nine-Year Cohort Study.

    PubMed

    Sutter, Raoul; Kaplan, Peter W

    2016-01-01

    Marked impairment of consciousness, brain lesion on neuroimaging, and nonreactive electroencephalographic (EEG) background activity are established outcome predictors in patients with hypoxic encephalopathy. In this observational cohort study, we aimed to assess the predictive value of clinical, neuroimaging and EEG characteristics for outcome in different types of acute nonhypoxic encephalopathic patients. All adult intensive care unit patients from a tertiary academic medical care center with clinical and EEG evidence of acute nonhypoxic encephalopathy were included from 2004 to 2012. Clinical data, neuroimaging studies, EEG characteristics, and outcome were assessed. In-hospital death was the main outcome. Median age of 262 patients was 65 years (range 18-98 years). Mortality was 12.6%. In Poisson regression analyses, older age (P=.02), intracranial hemorrhage (P=.008), coma (P=.012), and nonreactive EEG background activity (P<.0001) were independently associated with death with nonreactive EEG being the strongest predictor (relative risk 3.74; 95% confidence interval 2.02-6.91). Subgroup analysis revealed no significant effect modification for the predictive value of nonreactive EEG by the presence or absence of coma and different types of acute brain lesions. In conclusion, this study identifies and quantifies the independent predictive value of older age, intracranial hemorrhage, coma, and nonreactive EEG for death, in patients with different types of acute nonhypoxic encephalopathy. These results add further credence to the limited body of evidence that EEG provides important prognostic information in different types of acute encephalopathy not related to hypoxic brain injury. Further studies are warranted to analyze the robustness of this predictor in larger subpopulations with specific etiologies of acute nonhypoxic encephalopathies. PMID:25828484

  3. Translation of clinical prediction rules for febrile children to primary care practice: an observational cohort study

    PubMed Central

    van Ierland, Yvette; Elshout, Gijs; Berger, Marjolein Y; Vergouwe, Yvonne; de Wilde, Marcel; van der Lei, Johan; Mol, Henriëtte A; Oostenbrink, Rianne

    2015-01-01

    Background Clinical prediction rules (CPRs) to identify children with serious infections lack validation in low-prevalence populations, which hampers their implementation in primary care practice. Aim To evaluate the diagnostic value of published CPRs for febrile children in primary care. Design and setting Observational cohort study among febrile children (<16 years) who consulted five GP cooperatives (GPCs) in the Netherlands. Method Alarm signs of serious infection and clinical management were extracted from routine clinical practice data and manually recoded with a structured electronic data-entry program. Eight CPRs were selected from literature. CPR-variables were matched with alarm signs and CPRs were applied to the GPC-population. ‘Referral to emergency department (ED)’ was used as a proxy outcome measure for ‘serious infection’. CPR performance was assessed by calibration analyses, sensitivity, specificity, and area under the ROC-curve (ROC-area). Results A total of 9794 GPC-contacts were eligible, 54% male, median age 2.3 years (interquartile range 1.0–4.6 years) and 8.1% referred to ED. Frequencies of CPR-variables varied from 0.5% (cyanosis, drowsy) to 25% (temperature ≥40°C). Alarm signs frequently included in CPRs were ‘ill appearance’, ‘inconsolable’, and ‘abnormal circulatory or respiratory signs’. The height of the CPR’s predicted risks generally corresponded with being (or not being) referred to the ED in practice. However, calibration-slopes indicated that three CPRs underestimated the risk of serious infection in the GPC-population. Sensitivities ranged from 42% to 54%, specificities from 68% to 89%. ROC-areas ranged from 0.52 to 0.81, with best performance of CPRs for children aged <3 months. Conclusion Published CPRs performed moderately well in the primary out-of-hours care population. Advice is given on how to improve translation of CPRs to primary care practice. PMID:25824182

  4. Effect of polypharmacy, potentially inappropriate medications and anticholinergic burden on clinical outcomes: a retrospective cohort study

    PubMed Central

    Lu, Wan-Hsuan; Wen, Yu-Wen; Chen, Liang-Kung; Hsiao, Fei-Yuan

    2015-01-01

    Background: Polypharmacy, potentially inappropriate medications and anticholinergic burden (as assessed by the anticholinergic risk scale) are commonly used as quality indicators of pharmacotherapy in older adults. However, their role in clinical practice is undefined. We sought to investigate longitudinal changes in these indicators and their effects on clinical outcomes. Methods: We used Taiwan’s Longitudinal Health Insurance Database to retrieve quarterly information about drug use for people aged 65 years and older over a 10-year period. We analyzed the association between indicators and all-cause admission to hospital, fracture-specific admission to hospital and death using generalized estimating equations. Results: The study cohort comprised 59 042 older adults (65–74 yr: 39 358 [66.7%], 75–84 yr: 16 903 [28.6%], and ≥ 85 yr: 2781 [4.7%]). The mean changes in polypharmacy over the course of the study were greatest among patients aged 65–74 years (absolute difference +2.14, 95% confidence interval [CI] 2.10–2.19), then among those aged 75–84 yr (+1.79, 95% CI 1.70–1.88), and finally those aged 85 years and older (+0.71, 95% CI 0.36–1.05). The number of potentially inappropriate medications increased among patients aged 65–74 years (+0.16 [0.15–0.18]) and 75–84 years (+0.09 [0.06–0.08]), but decreased in those aged 85 years and older (−0.15 [−0.26 to −0.04]). Polypharmacy, potentially inappropriate medications and anticholinergic risk scale were each associated with an increased risk of admission to hospital, but not with death. In addition, both polypharmacy (5–9 drugs: odds ratio [OR] 1.18, 95% CI 1.12–1.24; ≥ 10 drugs: OR 1.54, 95% CI 1.42–1.66) and anticholinergic burden (score 1–2: 1.39, 95% CI 1.31–1.48; ≥ 3: 1.53, 95% CI 1.41–1.66) showed dose–response relations with fracture-specific admission to hospital. Interpretation: The total number of drugs taken (polypharmacy), number of potentially inappropriate

  5. Pre-clinical and clinical walking kinematics in female breeding pigs with lameness: A nested case-control cohort study.

    PubMed

    Stavrakakis, S; Guy, J H; Syranidis, I; Johnson, G R; Edwards, S A

    2015-07-01

    Gait profiles were investigated in a cohort of female pigs experiencing a lameness period prevalence of 29% over 17 months. Gait alterations before and during visually diagnosed lameness were evaluated to identify the best quantitative clinical lameness indicators and early predictors for lameness. Pre-breeding gilts (n= 84) were recruited to the study over a period of 6 months, underwent motion capture every 5 weeks and, depending on their age at entry to the study, were followed for up to three successive gestations. Animals were subject to motion capture in each parity at 8 weeks of gestation and on the day of weaning (28 days postpartum). During kinematic motion capture, the pigs walked on the same concrete walkway and an array of infra-red cameras was used to collect three dimensional coordinate data of reflective skin markers attached to the head, trunk and limb anatomical landmarks. Of 24 pigs diagnosed with lameness, 19 had preclinical gait records, whilst 18 had a motion capture while lame. Depending on availability, data from one or two preclinical motion capture 1-11 months prior to lameness and on the day of lameness were analysed. Lameness was best detected and evaluated using relative spatiotemporal gait parameters, especially vertical head displacement and asymmetric stride phase timing. Irregularity in the step-to-stride length ratio was elevated (deviation  ≥ 0.03) in young pigs which presented lameness in later life (odds ratio 7.2-10.8). PMID:25986130

  6. Ten-Year Mortality after a Breast Cancer Diagnosis in Women with Severe Mental Illness: A Danish Population-Based Cohort Study

    PubMed Central

    Ribe, Anette Riisgaard; Laurberg, Tinne; Laursen, Thomas Munk; Charles, Morten; Vedsted, Peter; Vestergaard, Mogens

    2016-01-01

    Background Breast cancer is the leading cause of cancer death in women worldwide. Nevertheless, it is unknown whether higher mortality after breast cancer contributes to the life-expectancy gap of 15 years in women with severe mental illness (SMI). Methods We estimated all-cause mortality rate ratios (MRRs) of women with SMI, women with breast cancer and women with both disorders compared to women with neither disorder using data from nationwide registers in Denmark for 1980–2012. Results The cohort included 2.7 million women, hereof 31,421 women with SMI (12,852 deaths), 104,342 with breast cancer (52,732 deaths), and 1,106 with SMI and breast cancer (656 deaths). Compared to women with neither disorder, the mortality was 118% higher for women with SMI (MRR: 2.18, 95% confidence interval (CI): 2.14–2.22), 144% higher for women with breast cancer (MRR: 2.44, 95% CI: 2.42–2.47) and 327% higher for women with SMI and breast cancer (MRR: 4.27, 95% CI: 3.98–4.57). Among women with both disorders, 15% of deaths could be attributed to interaction. In a sub-cohort of women with breast cancer, the ten-year all-cause-mortality was 59% higher after taking tumor stage into account (MRR: 1.59, 95% CI: 1.47–1.72) for women with versus without SMI. Conclusions The mortality among women with SMI and breast cancer was markedly increased. More information is needed to determine which factors might explain this excess mortality, such as differences between women with and without SMI in access to diagnostics, provision of care for breast cancer or physical comorbidity, health-seeking-behavior, and adherence to treatment. PMID:27462907

  7. Clinical Outcomes of Minimally Invasive Versus Open TLIF: A Propensity-Matched Cohort Study.

    PubMed

    Djurasovic, Mladen; Rouben, David P; Glassman, Steven D; Casnellie, Michael T; Carreon, Leah Y

    2016-01-01

    In this study, we compare intermediate-term outcomes in minimally invasive surgical transforaminal lumbar interbody fusion (MIS TLIF) to open TLIF. Sixty-four patients who underwent 1- to 2-level MIS TLIF with baseline, 1-, and 2-year outcome measures were identified. These were propensity-matched to a cohort of open TLIF patients based on age, body mass index, sex, smoking status, workers' compensation status, and preoperative outcome measures. At 1 year, both groups had similar improvements in pain and Short-Form 36 (SF-36) Physical Composite Summary (PCS), but the MIS TLIF group had a statistically significantly greater improvement in Oswestry Disability Index (ODI) compared with the open TLIF group. At 2 years, the MIS TLIF group had a statistically significantly greater improvement in pain and ODI compared with the open TLIF group, but no statistically significant difference in SF-36 PCS. Both MIS TLIF and open TLIF lead to significant improvements in clinical outcomes. At 1 year after surgery, MIS TLIF patients had greater improvements in ODI, and at 2 years after surgery, they had greater improvements in pain and ODI. This study showed that the perioperative advantages of MIS TLIF, such as less muscle dissection and faster recovery, continue to be beneficial 1 to 2 years after surgery. PMID:26991587

  8. Clinical Outcomes and Microbiological Characteristics of Severe Pneumonia in Cancer Patients: A Prospective Cohort Study

    PubMed Central

    Rabello, Ligia S. C. F.; Silva, Jose R. L.; Azevedo, Luciano C. P.; Souza, Ivens; Torres, Viviane B. L.; Rosolem, Maíra M.; Lisboa, Thiago; Soares, Marcio; Salluh, Jorge I. F.

    2015-01-01

    Introduction Pneumonia is the most frequent type of infection in cancer patients and a frequent cause of ICU admission. The primary aims of this study were to describe the clinical and microbiological characteristics and outcomes in critically ill cancer patients with severe pneumonia. Methods Prospective cohort study in 325 adult cancer patients admitted to three ICUs with severe pneumonia not acquired in the hospital setting. Demographic, clinical and microbiological data were collected. Results There were 229 (71%) patients with solid tumors and 96 (29%) patients with hematological malignancies. 75% of all patients were in septic shock and 81% needed invasive mechanical ventilation. ICU and hospital mortality rates were 45.8% and 64.9%. Microbiological confirmation was present in 169 (52%) with a predominance of Gram negative bacteria [99 (58.6%)]. The most frequent pathogens were methicillin-sensitive S. aureus [42 (24.9%)], P. aeruginosa [41(24.3%)] and S. pneumonia [21 (12.4%)]. A relatively low incidence of MR [23 (13.6%)] was observed. Adequate antibiotics were prescribed for most patients [136 (80.5%)]. In multivariate analysis, septic shock at ICU admission [OR 5.52 (1.92–15.84)], the use of invasive MV [OR 12.74 (3.60–45.07)] and poor Performance Status [OR 3.00 (1.07–8.42)] were associated with increased hospital mortality. Conclusions Severe pneumonia is associated with high mortality rates in cancer patients. A relatively low rate of MR pathogens is observed and severity of illness and organ dysfunction seems to be the best predictors of outcome in this population. PMID:25803690

  9. Incidence and clinical variables associated with streptococcal throat infections: a prospective diagnostic cohort study

    PubMed Central

    Little, Paul; Hobbs, FD Richard; Mant, David; McNulty, Cliodna AM; Mullee, Mark

    2012-01-01

    Background Management of pharyngitis is commonly based on features which are thought to be associated with Lancefield group A beta-haemolytic streptococci (GABHS) but it is debatable which features best predict GABHS. Non-group A strains share major virulence factors with group A, but it is unclear how commonly they present and whether their presentation differs. Aim To assess the incidence and clinical variables associated with streptococcal infections. Design and setting Prospective diagnostic cohort study in UK primary care. Method The presence of pathogenic streptococci from throat swabs was assessed among patients aged ≥5 years presenting with acute sore throat. Results Pathogenic streptococci were found in 204/597 patients (34%, 95% CI = 31 to 38%): 33% (68/204) were non-group A streptococci, mostly C (n = 29), G (n = 18) and B (n = 17); rarely D (n = 3) and Streptococcus pneumoniae (n = 1). Patients presented with similar features whether the streptococci were group A or non-group A. The features best predicting A, C or G beta-haemolytic streptococci were patient’s assessment of severity (odds ratio [OR] for a bad sore throat 3.31, 95% CI = 1.24 to 8.83); doctors’ assessment of severity (severely inflamed tonsils OR 2.28, 95% CI = 1.39 to 3.74); absence of a bad cough (OR 2.73, 95% CI = 1.56 to 4.76), absence of a coryza (OR 1.54, 95% CI = 0.99 to 2.41); and moderately bad or worse muscle aches (OR 2.20, 95% CI = 1.41 to 3.42). Conclusion Non-group A strains commonly cause streptococcal sore throats, and present with similar symptomatic clinical features to group A streptococci. The best features to predict streptococcal sore throat presenting in primary care deserve revisiting. PMID:23211183

  10. Predictors of suppurative complications for acute sore throat in primary care: prospective clinical cohort study

    PubMed Central

    Stuart, Beth; Hobbs, F D Richard; Butler, Chris C; Hay, Alastair D; Campbell, John; Delaney, Brendan; Broomfield, Sue; Barratt, Paula; Hood, Kerenza; Everitt, Hazel; Mullee, Mark; Williamson, Ian; Mant, David; Moore, Michael

    2013-01-01

    Objective To document whether elements of a structured history and examination predict adverse outcome of acute sore throat. Design Prospective clinical cohort. Setting Primary care. Participants 14 610 adults with acute sore throat (≤2 weeks’ duration). Main outcome measures Common suppurative complications (quinsy or peritonsillar abscess, otitis media, sinusitis, impetigo or cellulitis) and reconsultation with new or unresolving symptoms within one month. Results Complications were assessed reliably (inter-rater κ=0.95). 1.3% (177/13 445) of participants developed complications overall and 14.2% (1889/13 288) reconsulted with new or unresolving symptoms. Independent predictors of complications were severe tonsillar inflammation (documented among 13.0% (1652/12 717); odds ratio 1.92, 95% confidence interval 1.28 to 2.89) and severe earache (5% (667/13 323); 3.02, 1.91 to 4.76), but the model including both variables had modest prognostic utility (bootstrapped area under the receiver operator curve 0.61, 0.57 to 0.65), and 70% of complications (124/177) occurred when neither was present. Clinical prediction rules for bacterial infection (Centor criteria and FeverPAIN) also predicted complications, but predictive values were also poor and most complications occurred with low scores (67% (118/175) scoring ≤2 for Centor; 126/173 (73%) scoring ≤2 for FeverPAIN). Previous medical problems, sex, temperature, and muscle aches were independently but weakly associated with reconsultation with new or unresolving symptoms. Conclusion Important suppurative complications after an episode of acute sore throat in primary care are uncommon. History and examination and scores to predict bacterial infection cannot usefully identify those who will develop complications. Clinicians will need to rely on strategies such as safety netting or delayed prescription in managing the uncertainty and low risk of complications. PMID:24277339

  11. Evolution of prodromal clinical markers of Parkinson disease in a glucocerebrosidase mutation positive cohort

    PubMed Central

    Beavan, Michelle; McNeill, Alisdair; Proukakis, Christos; Hughes, Derralynn A; Mehta, Atul; Schapira, Anthony H V

    2015-01-01

    Importance Numerically, the most important genetic risk factor for the development of Parkinson disease (PD) is the presence of a glucocerebrosidase gene (GBA) mutation. Objective The purpose of this study was the longitudinal clinical evaluation of a GBA mutation positive cohort and the evolution of the prodromal features of PD. Design Individuals were participants in a study of the aetiology and prodrome of PD and have been re-evaluated in this 2 year follow-up report. Setting Clinic-based. Participants Type 1 GD patients and heterozygous GBA mutation positive carriers were recruited in 2010 from the Lysosomal Storage Disorder Unit at the Royal Free Hospital, London. Thirty previously diagnosed Type 1 GD patients, twenty-eight heterozygous GBA mutation carriers and twenty-six genetically unrelated controls were included. For both GD and carrier subjects, exclusion criteria included a diagnosis of PD or dementia and for controls, any existing neurological disease. Main Outcome(s) and Measure(s) Assessment was performed for clinical markers including hyposmia, rapid eye movement sleep behaviour disorder (RBD), depression, autonomic dysfunction, cognitive function and parkinsonian motor signs (UPDRS part III). Results Over 2 years, depression scores were significantly worse in heterozygotes (P = ·01), RBD scores were significantly worse in GD patients (P < ·001) and heterozygotes (P < ·001), and UPDRS III scores were significantly worse in GD patients (P < ·001) and heterozygotes (P < ·001). In controls, there was a small but significant deterioration in the UPDRS II score (P = ·006). At 2 years, olfactory and cognitive assessment scores were lower in GD patients and heterozygotes compared to controls, but did not differ significantly from baseline. When the results from GD patients and heterozygotes were combined, there was a significant deterioration from baseline in RBD, BDI, UPDRS II and III scores (in all, P < ·01), and at 2 years, significant

  12. Intake of alcohol may modify the risk for non-melanoma skin cancer: results of a large Danish prospective cohort study.

    PubMed

    Jensen, Allan; Birch-Johansen, Fatima; Olesen, Anne B; Christensen, Jane; Tjønneland, Anne; Kjær, Susanne K

    2012-12-01

    Alcohol has not been linked definitively to non-melanoma skin cancer. We examined whether alcohol intake affects the risks for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) using data on 54,766 persons enrolled in the prospective Diet, Cancer, and Health cohort. Statistical analyses were based on the Cox proportional hazards model. All hazard ratios (HRs) were multivariate adjusted. Adjustment for exposure to UVR was not possible, but all analyses were adjusted for factors related to susceptibility to UVR, including sun sensitivity, degree of freckling, and number of nevi. A total of 2,409 BCC cases and 198 SCC cases were diagnosed within a median follow-up of 11.4 years. Total current alcohol intake was not associated with BCC risk, but beverage-specific analyses showed an increased BCC risk associated with intake of wine (HR=1.05, 95% confidence interval (CI): 1.02-1.08, current average alcohol intake, per 10 g per day) and spirits (HR=1.11, 95% CI: 1.02-1.21) and a decreased risk with beer (HR=0.97, 95% CI: 0.93-1.00). No convincing associations were found between total alcohol intake and risk for SCC, perhaps because of the limited number of cases. Our findings indicate that alcohol intake may increase the risk for BCC, but the relations seemed to depend on beverage type. PMID:22696059

  13. An Update of the Mayo Clinic Cohort of Patients With Adult Primary Central Nervous System Vasculitis

    PubMed Central

    Salvarani, Carlo; Brown, Robert D.; Christianson, Teresa; Miller, Dylan V.; Giannini, Caterina; Huston, John; Hunder, Gene G.

    2015-01-01

    Abstract Primary central nervous system vasculitis (PCNSV) is an uncommon condition in which lesions are limited to vessels of the brain and spinal cord. Because the clinical manifestations are not specific, the diagnosis is often difficult, and permanent disability and death are frequent outcomes. This study is based on a cohort of 163 consecutive patients with PCNSV who were examined at the Mayo Clinic over a 29-year period from 1983 to 2011. The aim of the study was to define the characteristics of these patients, which represents the largest series in adults reported to date. A total of 105 patients were diagnosed by angiographic findings and 58 by biopsy results. The patients diagnosed by biopsy more frequently had at presentation cognitive dysfunction, greater cerebrospinal fluid total protein concentrations, less frequent cerebral infarcts, and more frequent leptomeningeal gadolinium-enhanced lesions on magnetic resonance imaging (MRI), along with less mortality and disability at last follow-up. The patients diagnosed by angiograms more frequently had at presentation hemiparesis or a persistent neurologic deficit or stroke, more frequent infarcts on MRI and an increased mortality. These differences were mainly related to the different size of the vessels involved in the 2 groups. Although most patients responded to therapy with glucocorticoids alone or in conjunction with cyclophosphamide and tended to improve during the follow-up period, an overall increased mortality rate was observed. Relapses occurred in one-quarter of the patients and were less frequent in patients treated with prednisone and cyclophosphamide compared with those treated with prednisone alone. The mortality rate and degree of disability at last follow-up were greater in those with increasing age, cerebral infarctions on MRI, angiographic large vessel involvement, and diagnosis made by angiography alone, but were lower in those with gadolinium-enhanced lesions on MRI and in those with

  14. Incidence of and risk factors for cognitive impairment in an early Parkinson disease clinical trial cohort

    PubMed Central

    Uc, E Y.; McDermott, M P.; Marder, K S.; Anderson, S W.; Litvan, I; Como, P G.; Auinger, P; Chou, K L.; Growdon, J C.

    2009-01-01

    Objective: To investigate the incidence of and risk factors for cognitive impairment in a large, well-defined clinical trial cohort of patients with early Parkinson disease (PD). Methods: The Mini-Mental State Examination (MMSE) was administered periodically over a median follow-up period of 6.5 years to participants in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism trial and its extension studies. Cognitive impairment was defined as scoring 2 standard deviations below age- and education-adjusted MMSE norms. Results: Cumulative incidence of cognitive impairment in the 740 participants with clinically confirmed PD (baseline age 61.0 ± 9.6 years, Hoehn-Yahr stage 1–2.5) was 2.4% (95% confidence interval: 1.2%–3.5%) at 2 years and 5.8% (3.7%–7.7%) at 5 years. Subjects who developed cognitive impairment (n = 46) showed significant progressive decline on neuropsychological tests measuring verbal learning and memory, visuospatial working memory, visuomotor speed, and attention, while the performance of the nonimpaired subjects (n = 694) stayed stable. Cognitive impairment was associated with older age, hallucinations, male gender, increased symmetry of parkinsonism, increased severity of motor impairment (except for tremor), speech and swallowing impairments, dexterity loss, and presence of gastroenterologic/urologic disorders at baseline. Conclusions: The relatively low incidence of cognitive impairment in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism study may reflect recruitment bias inherent to clinical trial volunteers (e.g., younger age) or limitations of the Mini-Mental State Examination–based criterion. Besides confirming known risk factors for cognitive impairment, we identified potentially novel predictors such as bulbar dysfunction and gastroenterologic/urologic disorders (suggestive of autonomic dysfunction) early in the course of the disease. GLOSSARY CI = confidence interval; COWA = Controlled Word Association

  15. Perinatal vitamin D levels are not associated with later risk of developing pediatric-onset inflammatory bowel disease: a Danish case-cohort study.

    PubMed

    Thorsen, Steffen U; Jakobsen, Christian; Cohen, Arieh; Lundqvist, Marika; Thygesen, Lau C; Pipper, Christian; Ascherio, Alberto; Svensson, Jannet

    2016-08-01

    Objective Basic and epidemiologic studies on inflammatory bowel disease (IBD) have suggested an association between vitamin D and IBD risk. Though, the literature on IBD - especially pediatric-onset IBD - and vitamin D is still in its cradle. We therefore wanted to examine if levels of 25(OH)D at birth were associated with increased risk of developing pediatric-onset IBD. Material and methods A case-cohort study composed of cases diagnosed with Crohn's disease, ulcerative colitis or indeterminate/unclassified colitis and healthy controls. Cases and controls were matched on date of birth and were born in the period 1981-2004. Cases were diagnosed before the age of 18 years. The concentration of 25(OH)D was assessed from neonatal dried blood spots using a highly sensitive liquid chromatography tandem mass spectrometry. Odds ratios (OR) were calculated using conditional logistic regression and two-way ANOVA were used to test for season and birth year 25(OH)D variations. A total of 384 matched pairs were included in the statistical analyses. Results No significant association were found between levels of 25(OH)D and IBD risk in the adjusted model (OR [95% CI] (per 25 nmol/L increase), 1.12 [0.88; 1.42], p = 0.35). 25(OH)D levels were found to fluctuate significantly with season (p < 0.001) and year (p < 0.001). Median/Q1-Q3 values for 25(OH)D were 27.1/16.5-39.5 nmol/L for cases and 25.7/16.1-39.4 nmol/L for controls. Conclusion Our study do not suggest that a window of vulnerability exist around time of birth in regards to 25(OH)D levels and later pediatric-onset IBD risk. PMID:26872831

  16. Tenofovir-associated renal dysfunction in clinical practice: An observational cohort from western India

    PubMed Central

    Patel, Ketan K.; Patel, Atul K.; Ranjan, Rajiv R.; Patel, Apurva R.; Patel, Jagdish K.

    2010-01-01

    Background: Tenofovir (TDF) is preferred nucleoside reverse transcriptase inhibitors (NRTI) for the treatment of human immunodeficiency virus infection because of its potency and safety. Renal toxicity with TDF use is low and comparable with other NRTI in clinical trials, but there are many case studies and small case series of renal dysfunction with TDF. Materials and Methods: This is an observational longitudinal cohort of patients started on a TDF-based regimen from January 2007 to April 2010. Patients were evaluated at baseline and with every follow-up visit for serum creatinine and calculated creatinine clearance (Cockroft-Gault formula). In addition to this, the patients were also subjected to test for serum potassium, phosphorous and urine examinations as and when indicated. Renal dysfunction was defined as rise in serum creatinine to more than the upper level of normal (>1.2 mg%). Results: Of 1,271 patients started on a TDF-containing antiretroviral treatment (ART) 83 (6.53%) developed renal dysfunction, of which 79 had impaired serum creatinine and five had Fanconi’s syndrome. Renal dysfunction was more common with boosted a protease inhibitor (PI) (9.44%)-based regimen as compared to a non- nucleoside reverse transcriptase inhibitors (NNRTI) (5.01%)-based regimen (P = 0.003). The mean decline in creatinine clearance from baseline was 22.27 ml/min. The median time to develop renal dysfunction was 154 (15–935) days. Serum creatinine returned to normal in all the patients after stopping TDF. Five patients presented with features suggestive of Fanconi’s syndrome without alteration in serum creatinine. Conclusion: TDF-based treatment is associated with mild but reversible renal dysfunction. Patients receiving PI/r are at a higher risk of renal dysfunction compared to those receiving NNRTI-based ART. Clinicians should be adviced to have intensive renal monitoring, including creatinine clearance, urine examination, K+ and phosphate levels at baseline and

  17. Clinical Characteristics of a Cohort of 244 Patients with Congenital Adrenal Hyperplasia

    PubMed Central

    Finkielstain, Gabriela P.; Kim, Mimi S.; Sinaii, Ninet; Nishitani, Miki; Van Ryzin, Carol; Hill, Suvimol C.; Reynolds, James C.; Hanna, Reem M.

    2012-01-01

    Context: Patients with congenital adrenal hyperplasia (CAH) often suffer from long-term complications secondary to chronic glucocorticoid therapy and suboptimal treatment regimens. Objective: The aim of the study was to describe clinical characteristics of a large cohort of pediatric and adult CAH patients. Design and Setting: We conducted a cross-sectional study of 244 CAH patients [183 classic, 61 nonclassic (NC)] included in a Natural History Study at the National Institutes of Health. Main Outcome Measure(s): Outcome variables of interest were height sd score, obesity, hypertensive blood pressure (BP), insulin resistance, metabolic syndrome, bone mineral density, hirsutism (females), and testicular adrenal rest (TART). Results: The majority had elevated or suppressed androgens, with varied treatment regimens. Mean adult height sd score was −1.0 ± 1.1 for classic vs. −0.4 ± 0.9 for NC patients (P = 0.015). Obesity was present in approximately one third of patients, across phenotypes. Elevated BP was more common in classic than NC patients (P ≤ 0.01); pediatric hypertensive BP was associated with suppressed plasma renin activity (P = 0.001). Insulin resistance was common in classic children (27%) and adults (38% classic, 20% NC); 18% of adults had metabolic syndrome. The majority (61%) had low vitamin D; 37% of adults had low bone mineral density. Hirsutism was common (32% classic; 59% NC women). TART was found in classic males (33% boys; 44% men). Conclusions: Poor hormonal control and adverse outcomes are common in CAH, necessitating new treatments. Routine monitoring of classic children should include measuring BP and plasma renin activity. Osteoporosis prophylaxis and TART screening should begin during childhood. A longitudinal study is under way. PMID:22990093

  18. Clinical and genetic features of cervical dystonia in a large multicenter cohort

    PubMed Central

    Vemula, Satya R.; Xiao, Jianfeng; Thompson, Misty M.; Perlmutter, Joel S.; Wright, Laura J.; Jinnah, H.A.; Rosen, Ami R.; Hedera, Peter; Comella, Cynthia L.; Weissbach, Anne; Junker, Johanna; Jankovic, Joseph; Barbano, Richard L.; Reich, Stephen G.; Rodriguez, Ramon L.; Berman, Brian D.; Chouinard, Sylvain; Severt, Lawrence; Agarwal, Pinky; Stover, Natividad P.

    2016-01-01

    Objective: To characterize the clinical and genetic features of cervical dystonia (CD). Methods: Participants enrolled in the Dystonia Coalition biorepository (NCT01373424) with initial manifestation as CD were included in this study (n = 1,000). Data intake included demographics, family history, and the Global Dystonia Rating Scale. Participants were screened for sequence variants (SVs) in GNAL, THAP1, and Exon 5 of TOR1A. Results: The majority of participants were Caucasian (95%) and female (75%). The mean age at onset and disease duration were 45.5 ± 13.6 and 14.6 ± 11.8 years, respectively. At the time of assessment, 68.5% had involvement limited to the neck, shoulder(s), and proximal arm(s), whereas 47.4% had dystonia limited to the neck. The remaining 31.5% of the individuals exhibited more extensive anatomical spread. A head tremor was noted in 62% of the patients. Head tremor and laryngeal dystonia were more common in females. Psychiatric comorbidities, mainly depression and anxiety, were reported by 32% of the participants and were more common in females. Family histories of dystonia, parkinsonian disorder, and tremor were present in 14%, 11%, and 29% of the patients, respectively. Pathogenic or likely pathogenic SVs in THAP1, TOR1A, and GNAL were identified in 8 participants (0.8%). Two individuals harbored novel missense SVs in Exon 5 of TOR1A. Synonymous and noncoding SVs in THAP1 and GNAL were identified in 4% of the cohort. Conclusions: Head tremor, laryngeal dystonia, and psychiatric comorbidities are more common in female participants with CD. Coding and noncoding variants in GNAL, THAP1, and TOR1A make small contributions to the pathogenesis of CD. PMID:27123488

  19. Early sedation and clinical outcomes of mechanically ventilated patients: a prospective multicenter cohort study

    PubMed Central

    2014-01-01

    Introduction Sedation overuse is frequent and possibly associated with poor outcomes in the intensive care unit (ICU) patients. However, the association of early oversedation with clinical outcomes has not been thoroughly evaluated. The aim of this study was to assess the association of early sedation strategies with outcomes of critically ill adult patients under mechanical ventilation (MV). Methods A secondary analysis of a multicenter prospective cohort conducted in 45 Brazilian ICUs, including adult patients requiring ventilatory support and sedation in the first 48 hours of ICU admissions, was performed. Sedation depth was evaluated after 48 hours of MV. Multivariate analysis was used to identify variables associated with hospital mortality. Results A total of 322 patients were evaluated. Overall, ICU and hospital mortality rates were 30.4% and 38.8%, respectively. Deep sedation was observed in 113 patients (35.1%). Longer duration of ventilatory support was observed (7 (4 to 10) versus 5 (3 to 9) days, P = 0.041) and more tracheostomies were performed in the deep sedation group (38.9% versus 22%, P = 0.001) despite similar PaO2/FiO2 ratios and acute respiratory distress syndrome (ARDS) severity. In a multivariate analysis, age (Odds Ratio (OR) 1.02; 95% confidence interval (CI) 1.00 to 1.03), Charlson Comorbidity Index >2 (OR 2.06; 95% CI, 1.44 to 2.94), Simplified Acute Physiology Score 3 (SAPS 3) score (OR 1.02; CI 95%, 1.00 to 1.04), severe ARDS (OR 1.44; CI 95%, 1.09 to 1.91) and deep sedation (OR 2.36; CI 95%, 1.31 to 4.25) were independently associated with increased hospital mortality. Conclusions Early deep sedation is associated with adverse outcomes and constitutes an independent predictor of hospital mortality in mechanically ventilated patients. PMID:25047960

  20. Clinical and molecular characterisation of hereditary dopamine transporter deficiency syndrome: an observational cohort and experimental study

    PubMed Central

    Kurian, Manju A; Li, Yan; Zhen, Juan; Meyer, Esther; Hai, Nebula; Christen, Hans-Jürgen; Hoffmann, Georg F; Jardine, Philip; von Moers, Arpad; Mordekar, Santosh R; O'Callaghan, Finbar; Wassmer, Evangeline; Wraige, Elizabeth; Dietrich, Christa; Lewis, Timothy; Hyland, Keith; Heales, Simon JR; Sanger, Terence; Gissen, Paul; Assmann, Birgit E; Reith, Maarten EA; Maher, Eamonn R

    2010-01-01

    Summary Background Dopamine transporter deficiency syndrome is the first identified parkinsonian disorder caused by genetic alterations of the dopamine transporter. We describe a cohort of children with mutations in the gene encoding the dopamine transporter (SLC6A3) with the aim to improve clinical and molecular characterisation, reduce diagnostic delay and misdiagnosis, and provide insights into the pathophysiological mechanisms. Methods 11 children with a biochemical profile suggestive of dopamine transporter deficiency syndrome were enrolled from seven paediatric neurology centres in the UK, Germany, and the USA from February, 2009, and studied until June, 2010. The syndrome was characterised by detailed clinical phenotyping, biochemical and neuroradiological studies, and SLC6A3 mutation analysis. Mutant constructs of human dopamine transporter were used for in-vitro functional analysis of dopamine uptake and cocaine-analogue binding. Findings Children presented in infancy (median age 2·5 months, range 0·5–7) with either hyperkinesia (n=5), parkinsonism (n=4), or a mixed hyperkinetic and hypokinetic movement disorder (n=2). Seven children had been initially misdiagnosed with cerebral palsy. During childhood, patients developed severe parkinsonism-dystonia associated with an eye movement disorder and pyramidal tract features. All children had raised ratios of homovanillic acid to 5-hydroxyindoleacetic acid in cerebrospinal fluid, of range 5·0–13·2 (normal range 1·3–4·0). Homozygous or compound heterozygous SLC6A3 mutations were detected in all cases. Loss of function in all missense variants was recorded from in-vitro functional studies, and was supported by the findings of single photon emission CT DaTSCAN imaging in one patient, which showed complete loss of dopamine transporter activity in the basal nuclei. Interpretation Dopamine transporter deficiency syndrome is a newly recognised, autosomal recessive disorder related to impaired dopamine

  1. Registry of the clinical characteristics of spondyloarthritis in a cohort of Egyptian population.

    PubMed

    Tayel, M Y; Soliman, E; El Baz, W F; El Labaan, A; Hamaad, Y; Ahmed, M H

    2012-09-01

    The aim of this study was to characterize the socioeconomic features, as well as disease activity and functional status, treatment use, and quality of life in a cohort of Egyptian population. All are measured by standard instruments. This is a descriptive multicenter; cross-sectional study included consecutive patients with spondyloarthritis (SpAs) diagnosed according to the European spondyloarthritis study group criteria. Four Egyptian centers participated (one from the Upper Egypt, one from the Delta, and two from the West Coast), all adopted the same criteria for patient assessment, and data were collected in the same data base over a 12-month duration. A total of 75 patients were included in the study. The series consisted of 34 ankylosing spondylitis (AS) patients (64%), 23 patients with psoriatic arthritis (45.3%), 15 patients with Juvenile onset AS (18.7%), 2 patients with reactive arthritis (2.7%), and one with inflammatory bowel disease-related arthritis (1.3%). There was predominance of male patients (84%). All were Caucasians; 13% from the Upper Egypt, and 87% from the Delta and West coast Egypt. Their mean age was 37.44 ± 12.8 years; mean disease duration was 11.85 ± 9.27 years. Pure axial disease was reported by 24% of the patients, and pure peripheral involvement was observed in 4%, while the mixed pattern (axial, peripheral, and entheseal) was observed in 34%. Dactylitis was detected in 9.3%, tarsitis in 8%, and enthesitis in 29.3%. The most common extra-articular manifestation was anterior uveitis, reported by 5.3% of patients. Human leukocytic antigen B27 (HLA-B27) was positive in 58.7% of the tested patients (n = 29). Mean Bath Ankylosing Spondylitis Disease activity Index (BASDAI) score was 4.16 ± 2.12, of which 22 patients had a score more than 4; mean Bath Ankylosing Spondylitis Functional Index 5.12 ± 2.40, mean BASMI 4.17 ± 2.95, mean BAS-GI 5.92 ± 2.00, and mean Health assessment questionnaire 1.10 ± 0.65. In addition, patients with

  2. Bariatric Surgery in the United Kingdom: A Cohort Study of Weight Loss and Clinical Outcomes in Routine Clinical Care

    PubMed Central

    Douglas, Ian J.; Bhaskaran, Krishnan; Batterham, Rachel L.; Smeeth, Liam

    2015-01-01

    Background Bariatric surgery is becoming a more widespread treatment for obesity. Comprehensive evidence of the long-term effects of contemporary surgery on a broad range of clinical outcomes in large populations treated in routine clinical practice is lacking. The objective of this study was to measure the association between bariatric surgery, weight, body mass index, and obesity-related co-morbidities. Methods and Findings This was an observational retrospective cohort study using data from the United Kingdom Clinical Practice Research Datalink. All 3,882 patients registered in the database and with bariatric surgery on or before 31 December 2014 were included and matched by propensity score to 3,882 obese patients without surgery. The main outcome measures were change in weight and body mass index over 4 y; incident diagnoses of type 2 diabetes mellitus (T2DM), hypertension, angina, myocardial infarction (MI), stroke, fractures, obstructive sleep apnoea, and cancer; mortality; and resolution of hypertension and T2DM. Weight measures were available for 3,847 patients between 1 and 4 mo, 2,884 patients between 5 and 12 mo, and 2,258 patients between 13 and 48 mo post-procedure. Bariatric surgery patients exhibited rapid weight loss for the first four postoperative months, at a rate of 4.98 kg/mo (95% CI 4.88–5.08). Slower weight loss was sustained to the end of 4 y. Gastric bypass (6.56 kg/mo) and sleeve gastrectomy (6.29 kg/mo) were associated with greater initial weight reduction than gastric banding (2.77 kg/mo). Protective hazard ratios (HRs) were detected for bariatric surgery for incident T2DM, 0.68 (95% CI 0.55–0.83); hypertension, 0.35 (95% CI 0.27–0.45); angina, 0.59 (95% CI 0.40–0.87);MI, 0.28 (95% CI 0.10–0.74); and obstructive sleep apnoea, 0.55 (95% CI 0.40–0.87). Strong associations were found between bariatric surgery and the resolution of T2DM, with a HR of 9.29 (95% CI 6.84–12.62), and between bariatric surgery and the resolution of

  3. Socio-demographic, clinical, and health-related factors associated with breast reconstruction - A nationwide cohort study.

    PubMed

    Bodilsen, Anne; Christensen, Søren; Christiansen, Peer; Damsgaard, Tine E; Zachariae, Robert; Jensen, Anders B

    2015-10-01

    We collected registry- and questionnaire-based data on socio-economic and health status, tumor- and treatment-related variables, and explored associations with receipt of reconstruction and information about treatment options in a nationwide cohort of Danish women, treated for primary breast cancer. A total of 594 women were available for analysis, 240 (40%) of these received reconstruction. Multivariate analyses showed that receipt of reconstruction was associated with 1) younger age at time of primary surgery (<36 years: OR = 10.04, [3.80-26.50], p < 0.001 and 36-49 years: OR = 2.48, [1.73-3.56], p < 0.001, compared to 50-60 year olds), 2) having received radiotherapy (OR = 0.57, [0.40-0.81], p = 0.002), 3) high income (Second quartile: OR = 1.74, [1.05-2.90], p = 0.033 and fourth quartile: OR = 2.18, [1.31-3.62], p = 0.003, compared with the lowest income quartile), and 4) ethnicity other than Danish (OR = 6.32, [1.58-25.36], p = 0.009). Health-related factors at the time of primary surgery (physical functioning, body mass index, smoking, use of alcohol, and comorbidity) were not associated with reconstruction. Odds of having received information about the option of reconstruction decreased by 8% per year of age in the multivariate analysis (OR = 0.92, [0.87-0.97], p = 0.003). In conclusion, younger age and not having been treated with radiotherapy was independently associated with reconstruction. In addition, higher income was also found to be associated with reconstruction despite free and equal access to reconstruction and healthcare in Denmark. Healthrelated factors were not associated with the use of reconstruction following mastectomy. Our findings underscore the need for physicians to ensure optimal level of information and accessibility to reconstruction for all women regardless of age, treatment, and socio-economic status. PMID:26139600

  4. Radiographic and Clinical Outcomes of the Treatment of Immature Permanent Teeth by Revascularization or Apexification: A Pilot Retrospective Cohort Study

    PubMed Central

    Alobaid, Adel S.; Cortes, Lina M.; Lo, Jeffery; Nguyen, Thuan T.; Albert, Jeffery; Abu-Melha, Abdulaziz S; Lin, Louis M.; Gibbs, Jennifer L.

    2014-01-01

    Introduction This retrospective cohort study compared clinical and radiographic outcomes of endodontic treatment performed in immature non-vital permanent teeth, by apexification (calcium hydroxide or apical barrier with Mineral Trioxide Aggregate (MTA)), versus revascularization. Methods A comprehensive chart review was performed to obtain a cohort of sequential previously completed cases with recalls. Clinical and radiographic data were collected for 31 treated teeth (19 revascularization and 12 apexification) with an average follow up time of 17 months and a recall rate of 63%. Tooth survival, success rate, and adverse events were analyzed. Changes in radiographic root length, width and area were quantified. Results The majority of treated teeth survived throughout the study period with 30/31 (97%) teeth surviving (18/19 (95%) revascularization, 12/12 apexification). Most cases were also clinically successful with 27/31 (87%) meeting criteria for success, (15/19 (78%) revascularization and 12/12 apexification; non-significant difference). A greater incidence of adverse events was observed in the revascularization group (8/19 (42%) versus 1/12 (11%) in apexification (Risk Ratio= 5.1, p=0.04, 95%CI (0.719, 35.48)). Although more revascularization cases than apexification cases demonstrated an increase in radiographic root area and width, the effect was not statistically significant. Conclusion In this study, revascularization was not superior to other apexification techniques in either clinical or radiographic outcomes. Studies with large subject cohorts, and long follow up periods are needed to evaluate outcomes of revascularization and apexification, while accounting for important co-variants relevant to clinical success. PMID:25069909

  5. Large D-Dimer Fluctuation in Normal Pregnancy: A Longitudinal Cohort Study of 4,117 Samples from 714 Healthy Danish Women

    PubMed Central

    Hedengran, Katrine K.; Andersen, Malene R.; Stender, Steen; Szecsi, Pal B.

    2016-01-01

    Introduction. D-dimer levels increase throughout pregnancy, hampering the usefulness of the conventional threshold for dismissing thromboembolism. This study investigates the biological fluctuation of D-dimer in normal pregnancy. Methods. A total of 801 healthy women with expected normal pregnancies were recruited. D-dimer was repeatedly measured during pregnancy, at active labor, and on the first and second postpartum days. Percentiles for each gestational week were calculated. Each individual D-dimer was normalized by transformation into percentiles for the relevant gestational age or delivery group. The range in percentage points during the pregnancy and the delivery was calculated, and reference intervals were calculated for each pregnancy trimester, during vaginal delivery and scheduled and emergency cesarean section, and for the first and second day postpartum. Results. D-dimer increased during pregnancy; the maximal fluctuation was approximately 20 percentile points in approximately half of the women. In one out of ten women, the D-dimer values fluctuated by more than 50 percentile points. Conclusions. Due to the biological variation in D-dimer within each individual woman during normal pregnancy, repeated D-dimer measurements are of no clinical use in the evaluation of thromboembolic events during pregnancy. PMID:27190521

  6. Existing data sources for clinical epidemiology: Scandinavian Cohort for osteonecrosis of the jaw – work in progress and challenges

    PubMed Central

    Schiodt, Morten; Larsson Wexell, Cecilia; Herlofson, Bente Brokstad; Giltvedt, Karen Marie; Norholt, Sven Erik; Ehrenstein, Vera

    2015-01-01

    Osteonecrosis of the jaw (ONJ) is a severe side effect associated with antiresorptive treatment. Monitoring of ONJ using routine databases in Scandinavian countries is a challenge owing to lack of valid algorithms and to heterogeneous referral practices. The aim of this paper is to describe the process of establishing a Scandinavian ONJ Cohort enrolling all ONJ cases related to antiresorptive treatment arising in Denmark, Norway, and Sweden between 2011 and 2019. The initial purpose of the cohort is to support an ongoing pharmacovigilance study of denosumab and zoledronic acid in Denmark, Norway, and Sweden. The three countries, with their 199 clinics, departments, and units of oral and maxillofacial surgery, both hospital-based and freestanding, differ somewhat in referral practices of the ONJ patients. By directly contacting all providers of care to ONJ patients in the three countries, we established a network for reporting incident cases to each country’s research database directly or through a member of the Scandinavian ONJ task force as a liaison. The task force includes a Scandinavian coordinator and three national coordinators collaborating directly with the clinics. A uniform ONJ registration form has been developed, and the relevant medical community has been informed either directly or through presentations at professional meetings. A website with study information is published in each country, and data entry is ongoing. This large-scale systematic uniform registration of ONJ cases in Denmark, Norway, and Sweden, with an underlying total population of more than 20 million people, merged into the Scandinavian ONJ Cohort, will contribute to better knowledge and understanding of this challenging group of patients, and ultimately, help improve patient care. The Scandinavian ONJ Cohort as a whole and its component national ONJ research databases may offer the potential for large-scale multinational intervention and safety studies in the future. PMID:25657594

  7. Changing relationships between smoking and psychiatric disorders across twentieth century birth cohorts: clinical and research implications.

    PubMed

    Talati, A; Keyes, K M; Hasin, D S

    2016-04-01

    As the risks of tobacco use become recognized and smoking becomes stigmatized, new smokers may be increasingly driven to smoke by biological or genetic vulnerabilities rather than social desirability. Given that genetic risk for deviant proneness is shared across other psychiatric and addictive disorders, we predicted that as rates of smoking decreased through the latter half of the twentieth century, associations between smoking and psychopathology would increase. Participants (N=25 412) from a large US study-the National Epidemiologic Survey on Alcohol and Related Conditions, NESARC-were interviewed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule - DSM-IV Version (AUDADIS-IV) and classified into one of five birth cohort decades (1940s to 1980s) and three smoking history (nonsmokers, never-dependent smokers and ever-dependent smokers) groups. We found that the prevalence of smoking decreased across the five birth cohorts, but associations of smoking with drug and AUDs, attention-deficit hyperactivity disorder, bipolar disorder and antisocial personality disorder, each increased monotonically in more recently born cohorts, even after adjusting for concurrent demographic and socioeconomic changes. For drug and AUDs, increases were observed among smokers both with and without a history of nicotine dependence; for other outcomes, increases were entirely driven by nicotine-dependent smokers. Findings suggest that smokers in more recent cohorts have disproportionately high psychiatric vulnerability, and may benefit from greater mental health screenings. Differentiating between casual and dependent smokers may further help prioritize those at greatest risk. Researchers should also be aware of potential variation in psychiatric comorbidity based on cohort of birth when defining groups of smokers, to minimize confounding. PMID:26809837

  8. The formation and design of the 'Acute Admission Database'- a database including a prospective, observational cohort of 6279 patients triaged in the emergency department in a larger Danish hospital

    PubMed Central

    2012-01-01

    Background Management and care of the acutely ill patient has improved over the last years due to introduction of systematic assessment and accelerated treatment protocols. We have, however, sparse knowledge of the association between patient status at admission to hospital and patient outcome. A likely explanation is the difficulty in retrieving all relevant information from one database. The objective of this article was 1) to describe the formation and design of the 'Acute Admission Database', and 2) to characterize the cohort included. Methods All adult patients triaged at the Emergency Department at Hillerød Hospital and admitted either to the observationary unit or to a general ward in-hospital were prospectively included during a period of 22 weeks. The triage system used was a Danish adaptation of the Swedish triage system, ADAPT. Data from 3 different data sources was merged using a unique identifier, the Central Personal Registry number; 1) Data from patient admission; time and date, vital signs, presenting complaint and triage category, 2) Blood sample results taken at admission, including a venous acid-base status, and 3) Outcome measures, e.g. length of stay, admission to Intensive Care Unit, and mortality within 7 and 28 days after admission. Results In primary triage, patients were categorized as red (4.4%), orange (25.2%), yellow (38.7%) and green (31.7%). Abnormal vital signs were present at admission in 25% of the patients, most often temperature (10.5%), saturation of peripheral oxygen (9.2%), Glasgow Coma Score (6.6%) and respiratory rate (4.8%). A venous acid-base status was obtained in 43% of all patients. The majority (78%) had a pH within the normal range (7.35-7.45), 15% had acidosis (pH < 7.35) and 7% had alkalosis (pH > 7.45). Median length of stay was 2 days (range 1-123). The proportion of patients admitted to Intensive Care Unit was 1.6% (95% CI 1.2-2.0), 1.8% (95% CI 1.5-2.2) died within 7 days, and 4.2% (95% CI 3.7-4.7) died within

  9. Anti-MDA5 autoantibodies in juvenile dermatomyositis identify a distinct clinical phenotype: a prospective cohort study

    PubMed Central

    2014-01-01

    Introduction The aim of this study was to define the frequency and associated clinical phenotype of anti-MDA5 autoantibodies in a large UK based, predominantly Caucasian, cohort of patients with juvenile dermatomyositis (JDM). Methods Serum samples and clinical data were obtained from 285 patients with JDM recruited to the UK Juvenile Dermatomyositis Cohort and Biomarker Study. The presence of anti-MDA5 antibodies was determined by immunoprecipitation and confirmed by ELISA using recombinant MDA5 protein. Results were compared with matched clinical data, muscle biopsies (scored by an experienced paediatric neuropathologist) and chest imaging (reviewed by an experienced paediatric radiologist). Results Anti-MDA5 antibodies were identified in 7.4% of JDM patients and were associated with a distinct clinical phenotype including skin ulceration (P = 0.03) oral ulceration (P = 0.01), arthritis (P <0.01) and milder muscle disease both clinically (as determined by Childhood Myositis Assessment Score (P = 0.03)) and histologically (as determined by a lower JDM muscle biopsy score (P <0.01)) than patients who did not have anti-MDA5 antibodies. A greater proportion of children with anti-MDA5 autoantibodies achieved disease inactivity at two years post-diagnosis according to PRINTO criteria (P = 0.02). A total of 4 out of 21 children with anti-MDA5 had interstitial lung disease; none had rapidly progressive interstitial lung disease. Conclusions Anti-MDA5 antibodies can be identified in a small but significant proportion of patients with JDM and identify a distinctive clinical sub-group. Screening for anti-MDA5 autoantibodies at diagnosis would be useful to guide further investigation for lung disease, inform on prognosis and potentially confirm the diagnosis, as subtle biopsy changes could otherwise be missed. PMID:24989778

  10. The value of the UK Clinical Aptitude Test in predicting pre-clinical performance: a prospective cohort study at Nottingham Medical School

    PubMed Central

    2010-01-01

    Background The UK Clinical Aptitude Test (UKCAT) was introduced in 2006 as an additional tool for the selection of medical students. It tests mental ability in four distinct domains (Quantitative Reasoning, Verbal Reasoning, Abstract Reasoning, and Decision Analysis), and the results are available to students and admissions panels in advance of the selection process. As yet the predictive validity of the test against course performance is largely unknown. The study objective was to determine whether UKCAT scores predict performance during the first two years of the 5-year undergraduate medical course at Nottingham. Methods We studied a single cohort of students, who entered Nottingham Medical School in October 2007 and had taken the UKCAT. We used linear regression analysis to identify independent predictors of marks for different parts of the 2-year preclinical course. Results Data were available for 204/260 (78%) of the entry cohort. The UKCAT total score had little predictive value. Quantitative Reasoning was a significant independent predictor of course marks in Theme A ('The Cell'), (p = 0.005), and Verbal Reasoning predicted Theme C ('The Community') (p < 0.001), but otherwise the effects were slight or non-existent. Conclusion This limited study from a single entry cohort at one medical school suggests that the predictive value of the UKCAT, particularly the total score, is low. Section scores may predict success in specific types of course assessment. The ultimate test of validity will not be available for some years, when current cohorts of students graduate. However, if this test of mental ability does not predict preclinical performance, it is arguably less likely to predict the outcome in the clinical years. Further research from medical schools with different types of curriculum and assessment is needed, with longitudinal studies throughout the course. PMID:20667093

  11. Clinical experience with BIAsp 30: Results from the Bangladesh cohort of the global A1chieve study.

    PubMed

    Latif, Z A; Pathan, M F; Mannan, M A; Siddiqui, M N I; Ashrafuzzaman, S M; Rahman, M M; Sobhan, M J

    2013-12-01

    The aim of A1chieve was to remedy the deficit of data on the efficacy and safety of insulin analogues in routine clinical care in less well-resourced developed countries. To present results from the Bangladesh cohort of the A1chieve study receiving BIAsp 30 ± oral anti diabetic drugs. A1chieve was a 6-month, observational study of 66,726 people with type 2 diabetes, started on insulin detemir, insulin aspart or biphasic insulin aspart (BIAsp 30) in 28 countries across four continents. A total of 1,093 subjects were recruited from 49 sites in Bangladesh and 580 subjects initiated on BIAsp 30 were studied. In the entire cohort, treatment with BIAsp 30 for 24 weeks significantly reduced mean HbA(1c) (2.8%, p < 0.001), fasting plasma glucose (4.0 mmol/L, p < 0.001) and post prandial plasma glucose (6.6 mmol/L, p < 0.001) levels from baseline. The rate of overall hypoglycaemic events in the entire cohort also reduced significantly at 24 weeks (1.86 to 0.02 events/person year, p < 0.0001). BIAsp 30 can be considered as a safe and effective option for initiating as well as intensifying insulin therapy for type 2 diabetes. PMID:26118154

  12. Record linkage to correct under-ascertainment of cancers in HIV cohorts: The Sinikithemba HIV clinic linkage project.

    PubMed

    Sengayi, Mazvita; Spoerri, Adrian; Egger, Matthias; Kielkowski, Danuta; Crankshaw, Tamaryn; Cloete, Christie; Giddy, Janet; Bohlius, Julia

    2016-09-15

    The surveillance of HIV-related cancers in South Africa is hampered by the lack of systematic collection of cancer diagnoses in HIV cohorts and the absence of HIV status in cancer registries. To improve cancer ascertainment and estimate cancer incidence, we linked records of adults (aged ≥ 16 years) on antiretroviral treatment (ART) enrolled at Sinikithemba HIV clinic, McCord Hospital in KwaZulu-Natal (KZN) with the cancer records of public laboratories in KZN province using probabilistic record linkage (PRL) methods. We calculated incidence rates for all cancers, Kaposi sarcoma (KS), cervix, non-Hodgkin's lymphoma and non-AIDS defining cancers (NADCs) before and after inclusion of linkage-identified cancers with 95% confidence intervals (CIs). A total of 8,721 records of HIV-positive patients were linked with 35,536 cancer records. Between 2004 and 2010, we identified 448 cancers, 82% (n = 367) were recorded in the cancer registry only, 10% (n = 43) in the HIV cohort only and 8% (n = 38) both in the HIV cohort and the cancer registry. The overall cancer incidence rate in patients starting ART increased from 134 (95% CI 91-212) to 877 (95% CI 744-1,041) per 100,000 person-years after inclusion of linkage-identified cancers. Incidence rates were highest for KS (432, 95% CI 341-555), followed by cervix (259, 95% CI 179-390) and NADCs (294, 95% CI 223-395) per 100,000 person-years. Ascertainment of cancer in HIV cohorts is incomplete, PRL is both feasible and essential for cancer ascertainment. PMID:27098265

  13. "Cancer 2015": A Prospective, Population-Based Cancer Cohort-Phase 1: Feasibility of Genomics-Guided Precision Medicine in the Clinic.

    PubMed

    Parisot, John P; Thorne, Heather; Fellowes, Andrew; Doig, Ken; Lucas, Mark; McNeil, John J; Doble, Brett; Dobrovic, Alexander; John, Thomas; James, Paul A; Lipton, Lara; Ashley, David; Hayes, Theresa; McMurrick, Paul; Richardson, Gary; Lorgelly, Paula; Fox, Stephen B; Thomas, David M

    2015-01-01

    "Cancer 2015" is a longitudinal and prospective cohort. It is a phased study whose aim was to pilot recruiting 1000 patients during phase 1 to establish the feasibility of providing a population-based genomics cohort. Newly diagnosed adult patients with solid cancers, with residual tumour material for molecular genomics testing, were recruited into the cohort for the collection of a dataset containing clinical, molecular pathology, health resource use and outcomes data. 1685 patients have been recruited over almost 3 years from five hospitals. Thirty-two percent are aged between 61-70 years old, with a median age of 63 years. Diagnostic tumour samples were obtained for 90% of these patients for multiple parallel sequencing. Patients identified with somatic mutations of potentially "actionable" variants represented almost 10% of those tumours sequenced, while 42% of the cohort had no mutations identified. These genomic data were annotated with information such as cancer site, stage, morphology, treatment and patient outcomes and health resource use and cost. This cohort has delivered its main objective of establishing an upscalable genomics cohort within a clinical setting and in phase 2 aims to develop a protocol for how genomics testing can be used in real-time clinical decision-making, providing evidence on the value of precision medicine to clinical practice. PMID:26529019

  14. Practical clinical skills assessment for a cohort of 680 2nd year human medicine students. Is it feasible?

    PubMed

    Wagner-Menghin, Michaela; Preusche, Ingrid; Schmidts, Michael

    2015-03-01

    In clinical skills training objective structured clinical examinations (OSCEs) are the method of choice to foster learning. Hence, implementing them is challenging and expensive. Thus it is investigated how an alternative procedure that keeps OSCE's essential elements, but assigns less stations to each student, works in terms of validity and justifiability.Data of n = 694 students, each taking five tasks drawn semi-randomized out of a pool of 26 tasks, strictly aligned with learning objectives, are analyzed. Despite unsurprisingly low overall reliability, a justifiable pass/fail decision is possible for 480 students (69 %). The remaining group (n = 210, 30 %) is indeed larger than with longer OSCEs, and would need ongoing assessment. The tasks' psychometric quality contributes to exams construct validity. Resource preserving short practical skills assessment is educationally valid and feasible with MedUniVienna's human medicine cohorts of n = 680. PMID:25724462

  15. Single-specificity anti-Ku antibodies in an international cohort of 2140 systemic sclerosis subjects: clinical associations

    PubMed Central

    Hoa, S.; Hudson, M.; Troyanov, Y.; Proudman, S.; Walker, J.; Stevens, W.; Nikpour, M.; Assassi, S.; Mayes, M.D.; Wang, M.; Baron, M.; Fritzler, M.J.

    2016-01-01

    Abstract Autoantibodies directed against the Ku autoantigen are present in systemic sclerosis (SSc) and have been associated with myositis overlap and interstitial lung disease (ILD). However, there is a paucity of data on the clinical correlates of anti-Ku antibodies in the absence of other SSc-specific antibodies. The aim of this study was to assess the clinical correlates of single-specificity anti-Ku in SSc. An international (Canada, Australia, USA, Mexico) cohort of 2140 SSc subjects was formed, demographic and clinical variables were harmonized, and sera were tested for anti-Ku using a line immunoassay. Associations between single-specificity anti-Ku antibodies (i.e., in isolation of other SSc-specific antibodies) and outcomes of interest, including myositis, ILD, and survival, were investigated. Twenty-four (1.1%) subjects had antibodies against Ku, and 13 (0.6%) had single-specificity anti-Ku antibodies. Subjects with single-specificity anti-Ku antibodies were more likely to have ILD (58% vs 34%), and to have increased creatine kinase levels (>3× normal) at baseline (11% vs 1%) and during follow-up (10% vs 2%). No difference in survival was noted in subjects with and without single-specificity anti-Ku antibodies. This is the largest cohort to date focusing on the prevalence and disease characteristics of single-specificity anti-Ku antibodies in subjects with SSc. These results need to be interpreted with caution in light of the small sample. International collaboration is key to understanding the clinical correlates of uncommon serological profiles in SSc. PMID:27583908

  16. Single-specificity anti-Ku antibodies in an international cohort of 2140 systemic sclerosis subjects: clinical associations.

    PubMed

    Hoa, S; Hudson, M; Troyanov, Y; Proudman, S; Walker, J; Stevens, W; Nikpour, M; Assassi, S; Mayes, M D; Wang, M; Baron, M; Fritzler, M J

    2016-08-01

    Autoantibodies directed against the Ku autoantigen are present in systemic sclerosis (SSc) and have been associated with myositis overlap and interstitial lung disease (ILD). However, there is a paucity of data on the clinical correlates of anti-Ku antibodies in the absence of other SSc-specific antibodies. The aim of this study was to assess the clinical correlates of single-specificity anti-Ku in SSc.An international (Canada, Australia, USA, Mexico) cohort of 2140 SSc subjects was formed, demographic and clinical variables were harmonized, and sera were tested for anti-Ku using a line immunoassay. Associations between single-specificity anti-Ku antibodies (i.e., in isolation of other SSc-specific antibodies) and outcomes of interest, including myositis, ILD, and survival, were investigated.Twenty-four (1.1%) subjects had antibodies against Ku, and 13 (0.6%) had single-specificity anti-Ku antibodies. Subjects with single-specificity anti-Ku antibodies were more likely to have ILD (58% vs 34%), and to have increased creatine kinase levels (>3× normal) at baseline (11% vs 1%) and during follow-up (10% vs 2%). No difference in survival was noted in subjects with and without single-specificity anti-Ku antibodies.This is the largest cohort to date focusing on the prevalence and disease characteristics of single-specificity anti-Ku antibodies in subjects with SSc. These results need to be interpreted with caution in light of the small sample. International collaboration is key to understanding the clinical correlates of uncommon serological profiles in SSc. PMID:27583908

  17. [Clinical and biological effectiveness of antiretroviral therapy in the ANRS 1215 cohort].

    PubMed

    De Beaudrap, P; Diouf, A; Bousso Niang, K

    2014-10-01

    In 1998, the cohort ANRS 1215 was launched in Senegal with one of the first African antiretroviral treatment programs. Four hundred forty four HIV-infected adults started on ART were included between 1998 and 2004, and followed up to 2010. Mortality before 6 months was 15.6/100 person-year (PY) and associated to the initial disease severity. It decreased to 3.36/100 PY thereafter. The cumulative risks of virologic failure at 60 months and of drug resistance at 48 months were 25% and 16%, respectively. PMID:24619515

  18. Frequency and Clinical Features of Dengue Infection in a Schoolchildren Cohort from Medellin, Colombia

    PubMed Central

    Restrepo, Berta Nelly; Piedrahita, Leidy Diana; Agudelo, Ivony Yireth; Parra-Henao, Gabriel; Osorio, Jorge E.

    2012-01-01

    To determine the incidence of dengue infection, we established active surveillance of febrile episodes in a cohort of schoolchildren from three schools in Medellin, Colombia. We followed a cohort of 2,379 schoolchildren in 2010 and followed 1,840 of these children the following year. During the follow-up time, 264 schoolchildren displayed 297 febrile episodes; of these, 23 episodes (7.7%) were caused by acute dengue infection. All four dengue serotypes were found, and all of the cases were mild. The most common symptoms in the dengue cases compared with those in other febrile illness were asthenia (96% versus 87%), anorexia (78% versus 57%), rhinorrhea (65.2% versus 58%), abdominal pain (56.5% versus 47.8%), arthralgia (43% versus 33%), and positive tourniquet test (13% versus 3%). This difference was not statistically significant. Pulse was elevated, and systolic arterial pressure was lower in dengue cases compared with other febrile illness (P < 0.05). Mosquito indexes were determined in 8 children's houses and in the schools. Aedes aegypti adults were found in both households and in schools, whereas Aedes aegypti larvae were found only in schools. These results showed an elevated dengue frequency in children, with symptoms similar to those of other febrile illness and transmission risk in households and schools. PMID:23304167

  19. Sorafenib treatment of radioiodine-refractory advanced thyroid cancer in daily clinical practice: a cohort study from a single center.

    PubMed

    Gallo, Marco; Michelon, Federica; Castiglione, Anna; Felicetti, Francesco; Viansone, Alessandro Adriano; Nervo, Alice; Zichi, Clizia; Ciccone, Giovannino; Piovesan, Alessandro; Arvat, Emanuela

    2015-08-01

    Treatment options for recurrent or metastatic differentiated thyroid cancer (DTC) refractory to radioactive iodine (RAI) are inadequate. Multitargeted kinase inhibitors have recently shown promising results in phase 2-3 studies. This retrospective study aimed to document our clinical experience on the effects of sorafenib in the setting of daily clinical practice. Retrospective study evaluating the efficacy and safety of sorafenib in a cohort of patients consecutively treated with sorafenib at a single center. Twenty patients with advanced RAI-refractory thyroid carcinoma were enrolled (March 2011-March 2014). Patients generally started with 400 mg of sorafenib twice daily, tapering the dose in case of side effects. Radiological response and toxicity were measured during follow-up, together with safety parameters. CT scans were performed by a single experienced radiologist every 3-4 months. Five patients stopped sorafenib within 90 days due to severe toxicities. Median progression-free survival was 248 days. Five patients had a partial response (PR), achieved in all cases within 3 months, whereas 5 had stable disease (SD) at 12 months. Durable response rate (PR plus SD) for at least 6 months was 50 %, among those who received sorafenib for at least 3 months. Commonest adverse events included skin toxicity, gastrointestinal and constitutional symptoms. In our cohort of patients with advanced RAI-refractory thyroid carcinoma, sorafenib confirmed antitumor activity leading to SD or PR in the majority of cases, at the expense of clinically relevant side effects. More effective and tolerable agents are still needed in the treatment of RAI-refractory DTC. PMID:25414068

  20. Self-reported preparedness for clinical work has increased among recent cohorts of UK-trained first-year doctors

    PubMed Central

    Lachish, Shelly; Goldacre, Michael J; Lambert, Trevor

    2016-01-01

    Introduction UK medical schools have made considerable efforts to ensure that graduates are well prepared for their first year of clinical work. We report the views of two recent cohorts of UK-trained doctors 1 year after graduation about whether their medical school prepared them well, and compare responses with earlier cohorts. Methods We surveyed doctors who qualified in 2011 and 2012 from all UK medical schools. We obtained their responses to the statement ‘My experience at medical school prepared me well for the jobs I have undertaken so far’ on a 5-point scale from ‘Strongly Agree’ to ‘Strongly Disagree’. Responses were compared with those of the UK graduates of 1999, 2000, 2002, 2005, 2008 and 2009, surveyed in the same way 1 year after graduation. Results The percentage of doctors who either ‘Agreed’ or ‘Strongly Agreed’ that they were well prepared doubled from 35% in 1999 to 70% in 2012, while the percentage who ‘Strongly Agreed’ with the statement increased fourfold. Perceptions of being well prepared have increased in graduates from almost every medical school. Variation between medical schools in self-reported preparedness of their graduates has decreased in recent cohorts. However, some large differences between medical schools remain. Significant differences in perceived preparedness remain between white and non-white doctors, but have diminished between men and women. Conclusions Our work contributes to growing evidence suggesting that changes to medical education in the UK are producing doctors who feel well prepared for the challenges of being a doctor, though further improvements could be made. PMID:26903664

  1. Staff perception of interprofessional working relationships after a work redesign intervention in a Danish orthopaedic hand unit outpatient clinic.

    PubMed

    de Beijer, Anke Elisabeth; Hansen, Torben Bæk; Stilling, Maiken; Jakobsen, Flemming

    2016-03-01

    There is evidence that clinical pathways improve quality of care; however, knowledge is limited concerning the influence on and the benefits experienced by the interprofessional teams working with these pathways. Our working methods in a hand unit in an orthopaedic outpatient clinic in Denmark were redesigned to include, among other changes, the introduction of clinical pathways. Changes included standardising treatment and communication methods, delegating tasks from medical specialists to nurses, and providing nurses with their own consultation room. Using focus group interviews before and after the implementation of the new working methods, we investigated staff-perceived experiences of the effects on working relationships and the utilisation of professional skills and attitudes, resulting from the mentioned change in working methods. The results were changes in daily communication methods among healthcare staff and improvements in the actual communication and collaborative problem solving skills concerning standard patients with simple hand pathology; however, there are still challenges for patients with more complex hand pathology. Though this new interprofessional arrangement improves the use of nurse and medical specialist professional competencies, it also requires a high degree of trust among the team members. PMID:27026187

  2. Preexisting Neutralizing Antibody Responses Distinguish Clinically Inapparent and Apparent Dengue Virus Infections in a Sri Lankan Pediatric Cohort

    PubMed Central

    Corbett, Kizzmekia S.; Katzelnick, Leah; Tissera, Hasitha; Amerasinghe, Ananda; de Silva, Aruna Dharshan; de Silva, Aravinda M.

    2015-01-01

    Dengue viruses (DENVs) are mosquito-borne flaviviruses that infect humans. The clinical presentation of DENV infection ranges from inapparent infection to dengue hemorrhagic fever and dengue shock syndrome. We analyzed samples from a pediatric dengue cohort study in Sri Lanka to explore whether antibody responses differentiated clinically apparent infections from clinically inapparent infections. In DENV-naive individuals exposed to primary DENV infections, we observed no difference in the quantity or quality of acquired antibodies between inapparent and apparent infections. Children who experienced primary infections had broad, serotype–cross-neutralizing antibody responses that narrowed in breadth to a single serotype over a 12-month period after infection. In DENV immune children who were experiencing a repeat infection, we observed a strong association between preexisting neutralizing antibodies and clinical outcome. Notably, children with preexisting monospecific neutralizing antibody responses were more likely to develop fever than children with cross-neutralizing responses. Preexisting DENV neutralizing antibodies are correlated with protection from dengue disease. PMID:25336728

  3. Clinical predictors for severe sepsis in patients with necrotizing fasciitis: an observational cohort study in northern Thailand

    PubMed Central

    Khamnuan, Patcharin; Chongruksut, Wilaiwan; Jearwattanakanok, Kijja; Patumanond, Jayanton; Tantraworasin, Apichat

    2015-01-01

    Background Necrotizing fasciitis (NF) is a life-threatening infection of skin and fascia. Its progress is extremely fast, with extensive necrosis. Delay in treatment, with subsequent huge soft tissue loss and associated severe sepsis, remains a major cause of death in the management of NF. Objective The aim of this study was to explore clinical characteristics that may be used to predict severe sepsis in patients with NF, in the context of routine clinical practice in northern Thailand. Methods A retrospective observational cohort study was conducted. The patient cohort in this study consisted of all patients who were diagnosed with NF by surgical or pathological confirmation. The follow-up period started with the admission date and ended with the discharge date. The clinical variables were collected from patients registered at three provincial hospitals in northern Thailand from 2009 to 2012. The clinical predictors for severe sepsis were analyzed using multivariable risk regression. Results A total of 1,452 patients were diagnosed with NF, either with severe sepsis (n=237 [16.3%]) or without severe sepsis (n=1,215 [83.7%]). From the multivariable analysis, female sex (relative risk [RR] =1.51; 95% confidence interval [CI] =1.04–2.20), diabetes mellitus (RR =1.40; 95% CI =1.25–1.58), chronic heart disease (RR =1.31; 95% CI =1.15–1.49), hemorrhagic bleb (RR =1.47; 95% CI =1.32–1.63), skin necrosis (RR =1.45; 95% CI =1.34–1.57), and serum protein <6 g/dL (RR =2.67; 95% CI =1.60–4.47) were all predictive factors for severe sepsis. Conclusion The clinical predictors for severe sepsis in patients with suspicion of NF included female sex, diabetes mellitus, chronic heart disease, hemorrhagic bleb, skin necrosis, and serum protein <6 d/dL. The risk ratio was much higher in patients with total protein less than 6 g/dL, which is associated with malnutrition. Therefore, provision of sufficient nutritional support and close monitoring for these clinical

  4. A Newfoundland cohort of familial and sporadic idiopathic pulmonary fibrosis patients: clinical and genetic features

    PubMed Central

    2012-01-01

    Background Idiopathic pulmonary fibrosis (IPF) is an adult-onset Idiopathic Interstitial Pneumonia (IIP) usually diagnosed between age 50 to 70 years. Individuals with Familial Pulmonary Fibrosis (FPF) have at least one affected first or second-degree relative and account for 0.5-20% of cases. Methods We ascertained and collected DNA samples from a large population-based cohort of IPF patients from Newfoundland, Canada. For each proband, a family history was documented and medical records were reviewed. Each proband was classified as familial (28 patients) or sporadic (50 patients) and all 78 probands were screened for variants in four highly penetrant, adult-onset PF genes (SFTPC, SFTPA2, TERT,TERC). Results Seventy-eight IPF probands were enrolled of whom 28 (35.9%) had a positive family history. These 28 familial patients led to the recruitment of an additional 49 affected relatives (total of 77 FPF patients). By age 60 years, 42% of the familial cohort had been diagnosed with PF compared with only 16% of the sporadic patient collection (χ2 = 8.77, p = 0.003). Mean age of diagnosis in the familial group was significantly younger than the sporadic group (61.4 years vs. 66.6 yrs, p = 0.012) with a wider age range of diagnosis (19–92 years compared with 47–82 years). Thirty-three of 77 (42.8%) FPF patients had a tissue diagnosis and all but five had usual interstitial pneumonia histology. Compared with other published case series, the familial IIP histologies were more homogeneous. Three of 28 familial probands (10.7%) and none of the 50 sporadic probands had pathogenic variants in the four genes tested. All three familial probands had mutations in TERT. Other phenotypes associated with telomerase deficiency were present in these families including cirrhosis, bone marrow hypoplasia and premature graying. Telomere length assays were performed on mutation carriers from two families and confirmed telomere-related deficiency. Conclusion The

  5. Outcome of a cohort of 300 patients with systemic lupus erythematosus attending a dedicated clinic for over two decades

    PubMed Central

    Moss, K; Ioannou, Y; Sultan, S; Haq, I; Isenberg, D

    2002-01-01

    Objective: To examine the mortality rate and causes of death in a cohort of 300 patients with systemic lupus erythematosus (SLE). Methods: A retrospective analysis was performed on all patients attending the SLE clinic between 1978 and 2000. Information was obtained on those patients lost to follow up. Cause of death was analysed and categorised as early (<5 years after diagnosis of SLE) and late (>5 years after diagnosis of SLE). Standardised mortality rates were obtained. Results: The patients were followed up for a median of 8.3 years. Seventy three (24%) patients were no longer followed up at the end of the study period, of whom 41 (14%) had died. Of the 32 patients lost to follow up, 14 were being actively followed up within the UK, 16 were followed up outside the UK, and two patients were untraceable. The most common cause of death was malignancy, which accounted for eight (20%) deaths, followed by infection and vascular disease, which accounted for seven (17%) deaths each. Conclusions: Malignancy was the most common cause of death. Cause of death varied depending on disease duration. Forty per cent of early deaths were due to SLE related renal disease, whereas 23% of late deaths were due to vascular causes. Death due to infection occurred throughout the follow up period. There was a fourfold increased risk of death in our cohort of patients with SLE compared with the general population. PMID:11959764

  6. A Clinical Algorithm to Identify HIV Patients at High Risk for Incident Active Tuberculosis: A Prospective 5-Year Cohort Study

    PubMed Central

    Lee, Susan Shin-Jung; Lin, Hsi-Hsun; Tsai, Hung-Chin; Su, Ih-Jen; Yang, Chin-Hui; Sun, Hsin-Yun; Hung, Chien-Chin; Sy, Cheng-Len; Wu, Kuan-Sheng; Chen, Jui-Kuang; Chen, Yao-Shen; Fang, Chi-Tai

    2015-01-01

    Background Predicting the risk of tuberculosis (TB) in people living with HIV (PLHIV) using a single test is currently not possible. We aimed to develop and validate a clinical algorithm, using baseline CD4 cell counts, HIV viral load (pVL), and interferon-gamma release assay (IGRA), to identify PLHIV who are at high risk for incident active TB in low-to-moderate TB burden settings where highly active antiretroviral therapy (HAART) is routinely provided. Materials and Methods A prospective, 5-year, cohort study of adult PLHIV was conducted from 2006 to 2012 in two hospitals in Taiwan. HAART was initiated based on contemporary guidelines (CD4 count < = 350/μL). Cox regression was used to identify the predictors of active TB and to construct the algorithm. The validation cohorts included 1455 HIV-infected individuals from previous published studies. Area under the receiver operating characteristic (ROC) curve was calculated. Results Seventeen of 772 participants developed active TB during a median follow-up period of 5.21 years. Baseline CD4 < 350/μL or pVL ≥ 100,000/mL was a predictor of active TB (adjusted HR 4.87, 95% CI 1.49–15.90, P = 0.009). A positive baseline IGRA predicted TB in patients with baseline CD4 ≥ 350/μL and pVL < 100,000/mL (adjusted HR 6.09, 95% CI 1.52–24.40, P = 0.01). Compared with an IGRA-alone strategy, the algorithm improved the sensitivity from 37.5% to 76.5%, the negative predictive value from 98.5% to 99.2%. Compared with an untargeted strategy, the algorithm spared 468 (60.6%) from unnecessary TB preventive treatment. Area under the ROC curve was 0.692 (95% CI: 0.587–0.798) for the study cohort and 0.792 (95% CI: 0.776–0.808) and 0.766 in the 2 validation cohorts. Conclusions A validated algorithm incorporating the baseline CD4 cell count, HIV viral load, and IGRA status can be used to guide targeted TB preventive treatment in PLHIV in low-to-moderate TB burden settings where HAART is routinely provided to all PLHIV. The

  7. Reproducibility of Vertebral Fracture Assessment Readings From Dual-energy X-ray Absorptiometry in Both a Population-based and Clinical Cohort: Cohen's and Uniform Kappa.

    PubMed

    Aubry-Rozier, Bérengère; Chapurlat, Roland; Duboeuf, François; Iglesias, Katia; Krieg, Marc-Antoine; Lamy, Olivier; Burnand, Bernard; Hans, Didier

    2015-01-01

    Vertebral fracture assessments (VFAs) using dual-energy X-ray absorptiometry increase vertebral fracture detection in clinical practice and are highly reproducible. Measures of reproducibility are dependent on the frequency and distribution of the event. The aim of this study was to compare 2 reproducibility measures, reliability and agreement, in VFA readings in both a population-based and a clinical cohort. We measured agreement and reliability by uniform kappa and Cohen's kappa for vertebral reading and fracture identification: 360 VFAs from a population-based cohort and 85 from a clinical cohort. In the population-based cohort, 12% of vertebrae were unreadable. Vertebral fracture prevalence ranged from 3% to 4%. Inter-reader and intrareader reliability with Cohen's kappa was fair to good (0.35-0.71 and 0.36-0.74, respectively), with good inter-reader and intrareader agreement by uniform kappa (0.74-0.98 and 0.76-0.99, respectively). In the clinical cohort, 15% of vertebrae were unreadable, and vertebral fracture prevalence ranged from 7.6% to 8.1%. Inter-reader reliability was moderate to good (0.43-0.71), and the agreement was good (0.68-0.91). In clinical situations, the levels of reproducibility measured by the 2 kappa statistics are concordant, so that either could be used to measure agreement and reliability. However, if events are rare, as in a population-based cohort, we recommend evaluating reproducibility using the uniform kappa, as Cohen's kappa may be less accurate. PMID:25439454

  8. Subtyping Somatic Tinnitus: A Cross-Sectional UK Cohort Study of Demographic, Clinical and Audiological Characteristics

    PubMed Central

    Ward, Jamie; Vella, Claire; Hoare, Derek J.; Hall, Deborah A.

    2015-01-01

    Somatic tinnitus is the ability to modulate the psychoacoustic features of tinnitus by somatic manoeuvres. The condition is still not fully understood and further identification of this subtype is essential, particularly for the purpose of establishing protocols for both its diagnosis and treatment. This study aimed to investigate the characteristics of somatic tinnitus within a large UK cohort using a largely unselected sample. We believe this to be relatively unique in comparison to current literature on the topic. This was investigated by using a total of 608 participant assessments from a set of recognised tinnitus and audiology measures. Results from a set of chi-square tests of association found that amongst the individuals with somatic tinnitus, a higher proportion had pulsatile tinnitus (different from heartbeat), were under the age of 40, reported variation in the loudness of their tinnitus and reported temporomandibular joint (TMJ) disorder. The same pattern of results was confirmed using a multivariate analysis of the data based on logistic regression. These findings have strong implications towards the profiling of somatic tinnitus as a distinct subtype of general tinnitus. PMID:25996779

  9. Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort.

    PubMed

    Shaw, Dominick E; Sousa, Ana R; Fowler, Stephen J; Fleming, Louise J; Roberts, Graham; Corfield, Julie; Pandis, Ioannis; Bansal, Aruna T; Bel, Elisabeth H; Auffray, Charles; Compton, Chris H; Bisgaard, Hans; Bucchioni, Enrica; Caruso, Massimo; Chanez, Pascal; Dahlén, Barbro; Dahlen, Sven-Erik; Dyson, Kerry; Frey, Urs; Geiser, Thomas; Gerhardsson de Verdier, Maria; Gibeon, David; Guo, Yi-Ke; Hashimoto, Simone; Hedlin, Gunilla; Jeyasingham, Elizabeth; Hekking, Pieter-Paul W; Higenbottam, Tim; Horváth, Ildikó; Knox, Alan J; Krug, Norbert; Erpenbeck, Veit J; Larsson, Lars X; Lazarinis, Nikos; Matthews, John G; Middelveld, Roelinde; Montuschi, Paolo; Musial, Jacek; Myles, David; Pahus, Laurie; Sandström, Thomas; Seibold, Wolfgang; Singer, Florian; Strandberg, Karin; Vestbo, Jorgen; Vissing, Nadja; von Garnier, Christophe; Adcock, Ian M; Wagers, Scott; Rowe, Anthony; Howarth, Peter; Wagener, Ariane H; Djukanovic, Ratko; Sterk, Peter J; Chung, Kian Fan

    2015-11-01

    U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p<0.001), with worse quality of life, and higher levels of anxiety and depression. They also had a higher incidence of nasal polyps and gastro-oesophageal reflux with lower lung function. Sputum eosinophil count was higher in severe asthma compared to mild/moderate asthma (median count 2.99% versus 1.05%; p=0.004) despite treatment with higher doses of inhaled and/or oral corticosteroids.Consistent with other severe asthma cohorts, U-BIOPRED is characterised by poor symptom control, increased comorbidity and airway inflammation, despite high levels of treatment. It is well suited to identify asthma phenotypes using the array of "omic" datasets that are at the core of this systems medicine approach. PMID:26357963

  10. Prevalence and incidence of liver enzyme elevations in a pooled oncology clinical trial cohort.

    PubMed

    Shantakumar, Sumitra; Landis, Sarah; Lawton, Andy; Hunt, Christine M

    2016-06-01

    Few epidemiologic studies describe longitudinal liver chemistry (LC) elevations in cancer patients. A population-based retrospective cohort was identified from 31 Phase 2-3 oncology trials (excluding targeted therapies) conducted from 1985 to 2005 to evaluate background rates of LC elevations in patients (n = 3998) with or without liver metastases. Patients with baseline liver metastases (29% of patients) presented with a 3% prevalence of alanine transaminase (ALT) ≥ 3x upper limits normal (ULN) and 0.2% prevalence of bilirubin ≥ 3xULN. During follow-up, the incidence (per 1000 person-months) of new onset ALT elevations ≥3xULN was 6.1 (95% CI: 4.5, 8.0) and 2.2 (95% CI: 0.9, 4.5) in patients without and with liver metastases, respectively. No new incident cases of ALT and bilirubin elevations suggestive of severe liver injury occurred among those with liver metastases; a single case occurred among those without metastasis. Regardless of the presence of liver metastases, LC elevations were rare in cancer patients during oncology trials, which may be due to enrollment criteria. Our study validates uniform thresholds for detection of LC elevations in oncology studies and serves as an empirical referent point for comparing liver enzyme abnormalities in oncology trials of novel targeted therapies. These data support uniform LC stopping criteria in oncology trials. PMID:27025923

  11. Next Generation Sequencing in the Clinic: a Patterns of Care Study in a Retrospective Cohort of Subjects Referred to a Genetic Medicine Clinic for Suspected Lynch Syndrome.

    PubMed

    Gallego, Carlos J; Perez, Matthew L; Burt, Amber; Amendola, Laura M; Shirts, Brian H; Pritchard, Colin C; Hisama, Fuki M; Bennett, Robin L; Veenstra, David L; Jarvik, Gail P

    2016-06-01

    Next generation sequencing (NGS) gene panels are increasingly used in medical genetics clinics for the evaluation of common inherited cancer syndromes, but the clinical efficacy of these tests, and the factors driving clinical providers to order them are unclear. We conducted a patterns-of-care study to compare patients evaluated with NGS gene panels with a reference group. We abstracted demographic, socioeconomic, and clinical information in a retrospective cohort of patients referred to a large medical genetics clinic for evaluation of inherited colorectal cancer and polyposis syndromes. Patients tested with NGS gene panels were more likely to be insured compared to the reference group (85.3 % vs. 69.2 %, p = 0.0068),less likely to have prior tumor tissue testing (29.4 % vs. 54.3 %, p = 0.0004), and less likely to have an abnormal tumor tissue test result (46.7 % vs. 74.5 %, p = 0.01). No significant differences were found between groups in age, gender, race, employment status, personal history of colorectal cancer, or proportion of patients fulfilling Lynch syndrome clinical criteria. Patients with NGS testing were less likely to have a pathogenic/likely pathogenic variant detected (13.7 % vs. 31.9 %, p = 0.002). Patients referred for NGS testing to evaluate inherited colorectal cancer/polyposis risk appear to undergo tumor tissue testing less frequently than non-NGS testing patients. Further studies are needed to assess the most effective and cost-effective approach to genomic diagnosis in this patient population. PMID:26637299

  12. Psoriasis and the Risk of Major Cardiovascular Events: Cohort Study Using the Clinical Practice Research Datalink.

    PubMed

    Parisi, Rosa; Rutter, Martin K; Lunt, Mark; Young, Helen S; Symmons, Deborah P M; Griffiths, Christopher E M; Ashcroft, Darren M

    2015-09-01

    The association between psoriasis and risk of major cardiovascular (CV) events (myocardial infarction, acute coronary syndrome, unstable angina, and stroke) is unclear. A cohort study with 48,523 patients with psoriasis and 208,187 controls was conducted. During a median follow-up of 5.2 years, 1,257 patients with psoriasis (2.59%) had a major CV event, compared with 4,784 controls (2.30%). In the multivariable analysis, inflammatory arthritis hazard ratio (HR) 1.36 (1.18-1.58), diabetes HR 1.18 (1.06-1.31), chronic kidney disease HR 1.18 (1.07-1.31), hypertension HR 1.37 (1.29-1.45), transient ischemic attack HR 2.74 (2.41-3.12), atrial fibrillation HR 1.54 (1.36-1.73), valvular heart disease HR 1.23 (1.05-1.44), thromboembolism 1.32 (1.17-1.49), congestive heart failure HR 1.57 (1.39-1.78), depression HR 1.16 (1.01-1.34), current smoker HR 2.18 (2.03-2.33), age (year) HR 1.07 (1.07-1.07), and male gender HR 1.83 (1.69-1.98) were statistically significant for the risk of major CV events. The age- and gender-adjusted HRs of a major CV event for psoriasis were 1.10 (1.04-1.17) and for severe psoriasis 1.40 (1.07-1.84), whereas the fully adjusted HRs were attenuated to 1.02 (0.95-1.08) and 1.28 (0.96-1.69). In conclusion, neither psoriasis nor severe psoriasis were associated with the short-to-medium term (over 3-5 years) risk of major CV events after adjusting for known cardiovascular disease risk factors. PMID:25742120

  13. Clinical and Brain Magnetic Resonance Imaging Features in a Cohort of Chinese Patients with Kearns-Sayre Syndrome

    PubMed Central

    Yu, Meng; Zhang, Zhe; Wang, Qing-Qing; Liu, Jing; Zuo, Yue-Huan; Yu, Lei; Xiao, Jiang-Xi; Zhang, Wei; Yuan, Yun; Wang, Zhao-Xia

    2016-01-01

    Background: Kearns-Sayre syndrome (KSS) is a mitochondrial DNA (mtDNA) deletion disorder characterized by a triad of onset before 20 years of age, ophthalmoplegia, and pigmentary retinopathy. The heart and central nervous system are commonly involved. We summarized clinical and brain magnetic resonance imaging (MRI) features of a cohort of Chinese KSS patients. Methods: Nineteen patients confirmed by muscle biopsy and mtDNA analysis were enrolled. We examined clinical profiles, mainly focusing on changes in electrocardiogram (ECG) and brain MRI. The correlation between genotype and phenotype was statistically analyzed. Results: The mean age of onset was 9.6 ± 4.3 years, with all developing the classic triad at the time of diagnosis. Heart conduction block was detected in 63.2%, with four initially presenting as bundle branch block and developing into complete atrioventricular block over 3–72 months. Brain MRI showed symmetric high-T2 signals in 100% of cerebral and cerebellar white matter, as well as brainstem, 46.7% of basal ganglia, and 53.3% of thalamus. There were two patterns of cerebral white matter involvements, one with selective subcortical U-fibers and the other with periventricular white matter. The size of mtDNA deletion did not significantly correlate with age of onset or percentage of ragged blue fibers on muscle pathology. Conclusions: The clinical features of KSS evolve dynamically, affecting the cardiac conduction system predominantly, highlighting the significance of ECG monitoring. Brain MRI showed changes involving both the white matter and deep gray nuclei. Clinical presentation or severity of muscle pathological changes is not related to the size of mtDNA deletions. PMID:27270536

  14. Birch pollen influence the severity of atopic eczema – prospective clinical cohort pilot study and ex vivo penetration study

    PubMed Central

    Fölster-Holst, Regina; Galecka, Jagoda; Weißmantel, Sigo; Dickschat, Ute; Rippke, Frank; Bohnsack, Kerstin; Werfel, Thomas; Wichmann, Katja; Buchner, Matthias; Schwarz, Thomas; Vogt, Annika; Lademann, Jürgen; Meinke, Martina C

    2015-01-01

    There is little clinical evidence for a correlation between the severity of atopic eczema (AE) and pollen exposition. To obtain more data, we performed a clinical cohort pilot study about the influence of pollen on AE between sensitized and nonsensitized subjects and an experimental study addressing the cutaneous penetration of pollen into the skin. Fifty-five patients were monitored during birch pollen season. To study the cutaneous penetration, grass pollen allergens were applied on excised skin and the uptake in CD1c-expressing dendritic cells was investigated. The correlation between environmental pollen load and severity of the Scoring Atopic Dermatitis (SCORAD) score and pruritus was observed, regardless of the status of sensitization. The sensitized group recovered significantly worse after the birch pollen season. Remarkably higher amounts of pollen allergens taken up by CD1c cells were detected in epidermal cells derived from skin explants with a disturbed epidermal barrier. These findings suggest an exacerbating role of pollen in AE utilizing the epidermal route. PMID:26604810

  15. Evaluation of clinical course and neurocognition in children with self-limited infantile epilepsy in a Turkish cohort study.

    PubMed

    Bozaykut, Abdulkadir; Aksoy, Halil Ural; Sezer, Rabia Gönül; Polat, Muzaffer

    2015-03-01

    The outcome of children with self-limited infantile epilepsy was reported to be normal psychosocial and cognitive development as a characteristic criterion. We aimed to investigate the clinical course and neurocognitive outcome in children with self-limited infantile epilepsy in a Turkish cohort. The clinical course, electroencephalographic (EEG) characteristics, neuroimaging, treatment, and outcome of children with self-limited infantile epilepsy were retrospectively analyzed. All infants were reevaluated with the Denver Developmental Screening Test in addition to neurologic examination. Of 44 patients, self-limited familial infantile epilepsy was diagnosed in 8 infants (18.2%) and self-limited nonfamilial infantile epilepsy in 28 (63.6%). Interictal EEGs and neurologic examinations were normal in all cases. Fine motor and gross motor skills, language, adaptive personal/social skills were near-normal in all patients with self-limited familial infantile epilepsy. Delay in language parameters was observed in 2 infants with self-limited nonfamilial infantile epilepsy. Language skills should be thoroughly evaluated with detailed neurocognitive screening tests in patients with self-limited infantile epilepsy. PMID:24958006

  16. Predictive validity of the UK clinical aptitude test in the final years of medical school: a prospective cohort study

    PubMed Central

    2014-01-01

    Background The UK Clinical Aptitude Test (UKCAT) was designed to address issues identified with traditional methods of selection. This study aims to examine the predictive validity of the UKCAT and compare this to traditional selection methods in the senior years of medical school. This was a follow-up study of two cohorts of students from two medical schools who had previously taken part in a study examining the predictive validity of the UKCAT in first year. Methods The sample consisted of 4th and 5th Year students who commenced their studies at the University of Aberdeen or University of Dundee medical schools in 2007. Data collected were: demographics (gender and age group), UKCAT scores; Universities and Colleges Admissions Service (UCAS) form scores; admission interview scores; Year 4 and 5 degree examination scores. Pearson’s correlations were used to examine the relationships between admissions variables, examination scores, gender and age group, and to select variables for multiple linear regression analysis to predict examination scores. Results Ninety-nine and 89 students at Aberdeen medical school from Years 4 and 5 respectively, and 51 Year 4 students in Dundee, were included in the analysis. Neither UCAS form nor interview scores were statistically significant predictors of examination performance. Conversely, the UKCAT yielded statistically significant validity coefficients between .24 and .36 in four of five assessments investigated. Multiple regression analysis showed the UKCAT made a statistically significant unique contribution to variance in examination performance in the senior years. Conclusions Results suggest the UKCAT appears to predict performance better in the later years of medical school compared to earlier years and provides modest supportive evidence for the UKCAT’s role in student selection within these institutions. Further research is needed to assess the predictive validity of the UKCAT against professional and behavioural

  17. Natural History of Anal Dysplasia in an HIV-Infected Clinical Care Cohort: Estimates Using Multi-State Markov Modeling

    PubMed Central

    Mathews, William C.; Agmas, Wollelaw; Cachay, Edward R.; Cosman, Bard C.; Jackson, Christopher

    2014-01-01

    Objectives (1) To model the natural history of anal neoplasia in HIV-infected patients using a 3-state Markov model of anal cancer pathogenesis, adjusting for cytology misclassification; and (2) to estimate the effects of selected time-varying covariates on transition probabilities. Design A retrospective cytology-based inception screening cohort of HIV-infected adults was analyzed using a 3-state Markov model of clinical pathogenesis of anal neoplasia. Methods Longitudinally ascertained cytology categories were adjusted for misclassification using estimates of cytology accuracy derived from the study cohort. Time-varying covariate effects were estimated as hazard ratios. Results (1) There was a moderate to high probability of regression of the high grade squamous intraepithelial lesion (HSIL) state (27–62%) at 2 years after initial cytology screening; (2) the probability of developing invasive anal cancer (IAC) during the first 2 years after a baseline HSIL cytology is low (1.9–2.8%); (3) infrared coagulation (IRC) ablation of HSIL lesions is associated with a 2.2–4.2 fold increased probability of regression to

  18. Generalized and Specific Cognitive Performance in Clinical High-Risk Cohorts: A Review Highlighting Potential Vulnerability Markers for Psychosis

    PubMed Central

    Brewer, Warrick J.; Wood, Stephen J.; Phillips, Lisa J.; Francey, Shona M.; Pantelis, Christos; Yung, Alison R.; Cornblatt, Barbara; McGorry, Patrick D.

    2006-01-01

    Cognitive deficits are a core feature of established psychotic illnesses. However, the association between cognition and emerging psychosis is less understood. While there is some evidence that cognitive deficits are present prior to the onset of psychosis, findings are not consistent. In this article we provide an overview of the more general cognitive findings available from genetic high-risk studies, retrospective studies, and birth cohort studies. We then focus the review on neuropsychological performance in clinically “at-risk” groups. Overall, general cognitive ability as assessed by established batteries appears to remain relatively intact in these ultra-high risk cohorts and is a poor predictor close to illness onset relative to other vulnerability factors. Further decline may occur with illness progression, more consistent with state relative to trait factors. In addition, most established cognitive tasks involve several relatively discrete cognitive subprocesses, where findings from general batteries of subtests may mask specific deficits. In this context, our review suggests that relatively specific olfactory identification and spatial working memory deficits exist prior to illness onset and may be more potent trait markers for psychosis than cognitively dense tasks such as verbal memory. Suggestions for further research address the importance of standardization of inclusion criteria and the maintenance of basic neuropsychological assessment to allow better comparison of findings across centers. Further, in order to better understand the aetiopathology of cognitive dysfunction in psychosis, more experimental, hypothesis-driven measures of discrete cognitive processes are required. Delineation of the relationship between specific cognitive ability and symptoms from data-driven approaches may improve our understanding of the role of cognition during psychosis onset. PMID:16782759

  19. Clinical Outcomes after Parathyroidectomy in a Nationwide Cohort of Patients on Hemodialysis

    PubMed Central

    Liu, Jiannong; Wetmore, James B.; Lowe, Kimberly A.; Do, Thy; Bradbury, Brian D.; Block, Geoffrey A.; Collins, Allan J.

    2015-01-01

    Background and objectives Patients receiving dialysis undergo parathyroidectomy to improve laboratory parameters in resistant hyperparathyroidism with the assumption that clinical outcomes will also improve. However, no randomized clinical trial data demonstrate the benefits of parathyroidectomy. This study aimed to evaluate clinical outcomes up to 1 year after parathyroidectomy in a nationwide sample of patients receiving hemodialysis. Design, setting, participants, & measurements Using data from the US Renal Data System, this study identified prevalent hemodialysis patients aged ≥18 years with Medicare as primary payers who underwent parathyroidectomy from 2007 to 2009. Baseline characteristics and comorbid conditions were assessed in the year preceding parathyroidectomy; clinical events were identified in the year preceding and the year after parathyroidectomy. After parathyroidectomy, patients were censored at death, loss of Medicare coverage, kidney transplant, change in dialysis modality, or 365 days. This study estimated cause-specific event rates for both periods and rate ratios comparing event rates in the postparathyroidectomy versus preparathyroidectomy periods. Results Of 4435 patients who underwent parathyroidectomy, 2.0% died during the parathyroidectomy hospitalization and the 30 days after discharge. During the 30 days after discharge, 23.8% of patients were rehospitalized; 29.3% of these patients required intensive care. In the year after parathyroidectomy, hospitalizations were higher by 39%, hospital days by 58%, intensive care unit admissions by 69%, and emergency room/observation visits requiring hypocalcemia treatment by 20-fold compared with the preceding year. Cause-specific hospitalizations were higher for acute myocardial infarction (rate ratio, 1.98; 95% confidence interval, 1.60 to 2.46) and dysrhythmia (rate ratio 1.4; 95% confidence interval1.16 to 1.78); fracture rates did not differ (rate ratio 0.82; 95% confidence interval 0.6 to

  20. Optimism and Recovery After Acute Coronary Syndrome: A Clinical Cohort Study

    PubMed Central

    Ronaldson, Amy; Molloy, Gerard J.; Wikman, Anna; Poole, Lydia; Kaski, Juan-Carlos; Steptoe, Andrew

    2015-01-01

    ABSTRACT Objective Optimism is associated with reduced cardiovascular mortality, but its impact on recovery after acute coronary syndrome (ACS) is poorly understood. We hypothesized that greater optimism would lead to more effective physical and emotional adaptation after ACS and would buffer the impact of persistent depressive symptoms on clinical outcomes. Methods This prospective observational clinical study took place in an urban general hospital and involved 369 patients admitted with a documented ACS. Optimism was assessed with a standardized questionnaire. The main outcomes were physical health status, depressive symptoms, smoking, physical activity, and fruit and vegetable consumption measured 12 months after ACS, and composite major adverse cardiac events (cardiovascular death, readmission with reinfarction or unstable angina, and coronary artery bypass graft surgery) assessed over an average of 45.7 months. Results We found that optimism predicted better physical health status 12 months after ACS independently of baseline physical health, age, sex, ethnicity, social deprivation, and clinical risk factors (B = 0.65, 95% confidence interval [CI] = 0.10–1.20). Greater optimism also predicted reduced risk of depressive symptoms (odds ratio = 0.82, 95% CI = 0.74–0.90), more smoking cessation, and more fruit and vegetable consumption at 12 months. Persistent depressive symptoms 12 months after ACS predicted major adverse cardiac events over subsequent years (odds ratio = 2.56, 95% CI = 1.16–5.67), but only among individuals low in optimism (optimism × depression interaction; p = .014). Conclusions Optimism predicts better physical and emotional health after ACS. Measuring optimism may help identify individuals at risk. Pessimistic outlooks can be modified, potentially leading to improved recovery after major cardiac events. PMID:25738438

  1. Analysis of Published Criteria for Clinically Inactive Disease in a Large Juvenile Dermatomyositis Cohort Shows That Skin Disease Is Underestimated

    PubMed Central

    Almeida, Beverley; Campanilho‐Marques, Raquel; Arnold, Katie; Pilkington, Clarissa A.; Wedderburn, Lucy R.; Armon, Kate; Briggs, Vanja; Ellis‐Gage, Joe; Roper, Holly; Watts, Joanna; Baildam, Eileen; Hanna, Louise; Lloyd, Olivia; McCann, Liza; Roberts, Ian; McGovern, Ann; Riley, Phil; Al‐Abadi, Eslam; Ryder, Clive; Scott, Janis; Southwood, Taunton; Thomas, Beverley; Amin, Tania; Burton, Deborah; Jackson, Gillian; Van Rooyen, Vanessa; Wood, Mark; Wyatt, Sue; Browne, Michael; Davidson, Joyce; Ferguson, Sue; Gardner‐Medwin, Janet; Martin, Neil; Waxman, Liz; Foster, Helen; Friswell, Mark; Jandial, Sharmila; Qiao, Lisa; Sen, Ethan; Smith, Eve; Stevenson, Vicky; Swift, Alison; Wade, Debbie; Watson, Stuart; Crate, Lindsay; Frost, Anna; Jordan, Mary; Mosley, Ellen; Satyapal, Rangaraj; Stretton, Elizabeth; Venning, Helen; Warrier, Kishore; Almeida, Beverley; Arnold, Katie; Beard, Laura; Brown, Virginia; Campanilho‐Marques, Raquel; Enayat, Elli; Glackin, Yvonne; Halkon, Elizabeth; Hasson, Nathan; Juggins, Audrey; Kassoumeri, Laura; Lunt, Sian; Maillard, Sue; Nistala, Kiran; Pilkington, Clarissa; Simou, Stephanie; Smith, Sally; Varsani, Hemlata; Wedderburn, Lucy; Murray, Kevin; Ioannou, John; Suffield, Linda; Al‐Obaidi, Muthana; Leach, Sam; Lee, Helen; Smith, Helen; Inness, Emma; Kendall, Eunice; Mayers, David; Wilkinson, Nick; Clinch, Jacqui; Pluess‐Hall, Helen

    2015-01-01

    Objective The Pediatric Rheumatology International Trials Organisation (PRINTO) recently published criteria for classification of patients with juvenile dermatomyositis (DM) as having clinically inactive disease. The criteria require that at least 3 of 4 conditions be met, i.e., creatine kinase level ≤150 units/liter, Childhood Myositis Assessment Scale score ≥48, Manual Muscle Testing in 8 muscles score ≥78, and physician's global assessment of overall disease activity (PGA) ≤0.2. The present study was undertaken to test these criteria in a UK cohort of patients with juvenile DM. Methods We assessed 1,114 patient visits for the 4 items in the PRINTO criteria for clinically inactive disease. Each visit was analyzed to determine whether skin disease was present. The Disease Activity Score (DAS) for juvenile DM was determined in 59 patients. Results At 307 of the 1,114 visits, clinically inactive disease was achieved based on the 3 muscle criteria (but with a PGA of >0.2); rash was present at 65.8% of these visits and nailfold capillary abnormalities at 35.2%. When PGA ≤0.2 was one of the 3 criteria that were met, the frequency of skin signs was significantly lower (rash in 23.1% and nailfold capillary abnormalities in 8.7%). If PGA was considered an essential criterion for clinically inactive disease (P‐CID), patients with active skin disease were less likely to be categorized as having clinically inactive disease (a median DAS skin score of 0 [of a possible maximum of 9] in visits where the PGA was ≤0.2, versus a median DAS skin score of 4 in patients meeting the 3 muscle criteria [with a PGA of >0.2]; P < 0.001). Use of the P‐CID led to improvements in the positive predictive value and the positive likelihood ratio (85.4% and 11.0, respectively, compared to 72.9% and 5.1 with the current criteria). Conclusion There was a high frequency of skin disease among patients with juvenile DM who did not meet the PGA criterion for inactive disease but met

  2. The effect of early, comprehensive genomic testing on clinical care in neonatal diabetes: an international cohort study

    PubMed Central

    De Franco, Elisa; Flanagan, Sarah E; Houghton, Jayne AL; Allen, Hana Lango; Mackay, Deborah JG; Temple, I Karen; Ellard, Sian; Hattersley, Andrew T

    2015-01-01

    Summary Background Traditional genetic testing focusses on analysis of one or a few genes according to clinical features; this approach is changing as improved sequencing methods enable simultaneous analysis of several genes. Neonatal diabetes is the presenting feature of many discrete clinical phenotypes defined by different genetic causes. Genetic subtype defines treatment, with improved glycaemic control on sulfonylurea treatment for most patients with potassium channel mutations. We investigated the effect of early, comprehensive testing of all known genetic causes of neonatal diabetes. Methods In this large, international, cohort study, we studied patients with neonatal diabetes diagnosed with diabetes before 6 months of age who were referred from 79 countries. We identified mutations by comprehensive genetic testing including Sanger sequencing, 6q24 methylation analysis, and targeted next-generation sequencing of all known neonatal diabetes genes. Findings Between January, 2000, and August, 2013, genetic testing was done in 1020 patients (571 boys, 449 girls). Mutations in the potassium channel genes were the most common cause (n=390) of neonatal diabetes, but were identified less frequently in consanguineous families (12% in consanguineous families vs 46% in non-consanguineous families; p<0·0001). Median duration of diabetes at the time of genetic testing decreased from more than 4 years before 2005 to less than 3 months after 2012. Earlier referral for genetic testing affected the clinical phenotype. In patients with genetically diagnosed Wolcott-Rallison syndrome, 23 (88%) of 26 patients tested within 3 months from diagnosis had isolated diabetes, compared with three (17%) of 18 patients referred later (>4 years; p<0·0001), in whom skeletal and liver involvement was common. Similarly, for patients with genetically diagnosed transient neonatal diabetes, the diabetes had remitted in only ten (10%) of 101 patients tested early (<3 months) compared with 60

  3. Demographics, clinical disease characteristics, and quality of life in a large cohort of psoriasis patients with and without psoriatic arthritis

    PubMed Central

    Truong, B; Rich-Garg, N; Ehst, BD; Deodhar, AA; Ku, JH; Vakil-Gilani, K; Danve, A; Blauvelt, A

    2015-01-01

    Innovation What is already known about the topic: psoriasis (PsO) is a common skin disease with major impact on quality of life (QoL). Patient-reported data on QoL from large number of PsO patients with and without psoriatic arthritis (PsA) are limited. What this study adds: In a large cohort referred to a university psoriasis center, patients with PsO and concomitant PsA (~30% in this group) had greater degrees of skin and nail involvement and experienced greater negative impacts on QoL. Despite large numbers of patients with moderate-to-severe disease, use of systemic therapy by community practitioners was uncommon. Background PsO and PsA are common diseases that have marked adverse impacts on QoL. The disease features and patient-reported QoL data comparing PsO and PsA patients are limited. Objective To identify and compare demographics, clinical disease characteristics, and QoL scores in a large cohort of PsO patients with and without PsA. Methods All PsO patients seen in a psoriasis specialty clinic, named the Center of Excellence for Psoriasis and Psoriatic Arthritis, were enrolled in an observational cohort. Demographic, QoL, and clinical data were collected from patient-reported questionnaires and from physical examinations performed by Center of Excellence for Psoriasis and Psoriatic Arthritis dermatologists and a rheumatologists. Cross sectional descriptive data were collected and comparisons between patients with PsO alone and those with concomitant PsA are presented. Results A total of 568 patients were enrolled in the database. Mean age of PsO onset was 28 years and mean disease duration was 18 years. Those with family history had an earlier onset of PsO by ~7 years. Mean body surface area involvement with PsO was 14%. Mean body mass index was 30.7. Prevalence of PsA was 29.8%. PsA patients had a higher mean body surface area compared to patients with PsO alone (16.7% vs 13.4%, P<0.05), higher prevalence of psoriatic nail changes (54.4% vs 36%, P<0

  4. MFN2-related genetic and clinical features in a cohort of Chinese CMT2 patients.

    PubMed

    Xie, Yongzhi; Li, Xiaobo; Liu, Lei; Hu, Zhengmao; Huang, Shunxiang; Zhan, Yajin; Zi, Xiaohong; Xia, Kun; Tang, Beisha; Zhang, Ruxu

    2016-03-01

    Charcot-Marie-Tooth disease 2A (CMT2A), caused by mutations in the mitofusin 2 gene (MFN2), is the most common CMT2 subtype. The aim of our study is to assess the frequency and summarize the genetic and clinical characteristics of Chinese CMT2A patients. A total of 17 coding exons of MFN2 were detected by direct sequencing in 82 unrelated Chinese families diagnosed as CMT2. Clinical evaluations were analyzed among CMT2A patients. We identified 14 missense variants in 9 sporadic and 6 familial cases, including four novel mutations (T129A, S249F, Q367P, and Q674L), 4 known mutations (R94W, R94Q, T105M, C132Y, M376V and Q751X), and 4 rare missense variants (K120E, C217F, K307E and T356S). A total of 23 patients had early-onset phenotype. Two patients had a CMTNS score of 0 to 10; 16 had a score of 11 to 20; and 7 had a score greater than 20. Five patients were confirmed a de novo origin. Six of 14 variants were located or closed to the GTPase domain. We report four novel mutations and four rare missense variants. MFN2 mutations account for 18% of CMT2 families in mainland China. The common characteristics of Chinese pedigree are early disease onset and moderate phenotypes. PMID:26801520

  5. Clinical characteristics associated with adverse events in patients with exacerbation of chronic obstructive pulmonary disease: a prospective cohort study

    PubMed Central

    Stiell, Ian G.; Clement, Catherine M.; Aaron, Shawn D.; Rowe, Brian H.; Perry, Jeffrey J.; Brison, Robert J.; Calder, Lisa A.; Lang, Eddy; Borgundvaag, Bjug; Forster, Alan J.; Wells, George A.

    2014-01-01

    Background: To assist physicians with difficult decisions about hospital admission for patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) presenting in the emergency department, we sought to identify clinical characteristics associated with serious adverse events. Methods: We conducted this prospective cohort study in 6 large Canadian academic emergency departments. Patients were assessed for standardized clinical variables and then followed for serious adverse events, defined as death, intubation, admission to a monitored unit or new visit to the emergency department requiring admission. Results: We enrolled 945 patients, of whom 354 (37.5%) were admitted to hospital. Of 74 (7.8%) patients with a subsequent serious adverse event, 36 (49%) had not been admitted after the initial emergency visit. Multivariable modelling identified 5 variables that were independently associated with adverse events: prior intubation, initial heart rate ≥ 110/minute, being too ill to do a walk test, hemoglobin < 100 g/L and urea ≥ 12 mmol/L. A preliminary risk scale incorporating these and 5 other clinical variables produced risk categories ranging from 2.2% for a score of 0 to 91.4% for a score of 10. Using a risk score of 2 or higher as a threshold for admission would capture all patients with a predicted risk of adverse events of 7.2% or higher, while only slightly increasing admission rates, from 37.5% to 43.2%. Interpretation: In Canada, many patients with COPD suffer a serious adverse event or death after being discharged home from the emergency department. We identified high-risk characteristics and developed a preliminary risk scale that, once validated, could be used to stratify the likelihood of poor outcomes and to enable rational and safe admission decisions. PMID:24549125

  6. Risk factors for hip-related clinical signs in a prospective cohort study of four large dog breeds in Norway.

    PubMed

    Krontveit, Randi I; Trangerud, Cathrine; Sævik, Bente K; Skogmo, Hege K; Nødtvedt, Ane

    2012-02-01

    We conducted a prospective cohort study including privately owned dogs from the breeds Newfondland (NF), Labrador Retriever (LR), Leonberger (LEO), and Irish Wolfhound (IW) followed from birth until age 9 yrs. We wanted to investigate whether radiological hip dysplasia status given at approximately age 12-18 mos and other factors during growth influenced development of clinical signs due to hip-joint disease necessitating veterinary consultation. Whether or not such signs occurred due to hip dysplasia or due to secondary or primary DJD could not be distinguished, and we therefore used the term "owner-reported veterinary-diagnosed hip-related clinical signs" ("the event"). The included dogs were followed from birth to the event or until a maximum of 9 yrs of age. Our objectives were to describe breed differences in time to incidence and to evaluate potential risk factors for the time to event. We used Kaplan-Meier curves to describe time to incidence, and potential risk factors were assessed by use of a Cox proportional-hazards model. We enrolled 494 dogs from 103 litters, and 46 dogs were reported as having had the event during the observation period. We observed a significant time-varying effect (TVE): LR and LEO developed clinical signs later in life than NF. If the radiological hip status was either mild, moderate, or severe the hazard of experiencing the event was significantly increased. Access to off-leash exercise at age 12 mos decreased the hazard of the event, and the hazard varied by litter. The findings supported the hypothesis that radiological hip status at screening and exercise conditions during growth influenced the time to incidence of the event and that there were breed differences in time to the event. PMID:21982689

  7. Educational Level, Anticoagulation Quality, and Clinical Outcomes in Elderly Patients with Acute Venous Thromboembolism: A Prospective Cohort Study.

    PubMed

    Hofmann, Eveline; Faller, Nicolas; Limacher, Andreas; Méan, Marie; Tritschler, Tobias; Rodondi, Nicolas; Aujesky, Drahomir

    2016-01-01

    Whether the level of education is associated with anticoagulation quality and clinical outcomes in patients with acute venous thromboembolism (VTE) is uncertain. We thus aimed to investigate the association between educational level and anticoagulation quality and clinical outcomes in elderly patients with acute VTE. We studied 817 patients aged ≥65 years with acute VTE from a Swiss prospective multicenter cohort study (09/2009-12/2013). We defined three educational levels: 1) less than high school, 2) high school, and 3) post-secondary degree. The primary outcome was the anticoagulation quality, expressed as the percentage of time spent in the therapeutic INR range (TTR). Secondary outcomes were the time to a first recurrent VTE and major bleeding. We adjusted for potential confounders and periods of anticoagulation. Overall, 56% of patients had less than high school, 25% a high school degree, and 18% a post-secondary degree. The mean percentage of TTR was similar across educational levels (less than high school, 61%; high school, 64%; and post-secondary, 63%; P = 0.36). Within three years of follow-up, patients with less than high school, high school, and a post-secondary degree had a cumulative incidence of recurrent VTE of 14.2%, 12.9%, and 16.4%, and a cumulative incidence of major bleeding of 13.3%, 15.1%, and 15.4%, respectively. After adjustment, educational level was neither associated with anticoagulation quality nor with recurrent VTE or major bleeding. In elderly patients with VTE, we did not find an association between educational level and anticoagulation quality or clinical outcomes. PMID:27606617

  8. Incidence Rates of Clinically Significant Tinnitus: 10-Year Trend From a Cohort Study in England

    PubMed Central

    Wallenhorst, Christopher; McFerran, Don; Hall, Deborah A.

    2015-01-01

    Objective: To investigate the incidence of tinnitus that burdens the health service in England. Design: This was an observational study of 4.7 million residents of England under 85 years of age who were at risk for developing clinically significant tinnitus (sigT). SigT was defined by a discharge from hospital with a primary diagnosis of tinnitus, or a primary care recording of tinnitus with subsequent related medical follow-up within 28 days. The database used was the Clinical Practice Research Datalink and individual records were linked to additional data from the Hospital Episode Statistics. The observational period was from January 1, 2002 to December 31, 2011. Age-, gender-, and calendar year-specific incidence rates for and cumulative incidences of sigT were estimated and a projection of new cases of sigT between 2012 and 2021 was performed. Results: There were 14,303 incident cases of sigT identified among 26.5 million person-years of observation. The incidence rate was 5.4 new cases of sigT per 10,000 person-years (95% confidence interval: 5.3 to 5.5). The incidence rate did not depend on gender but increased with age, peaking at 11.4 per 10,000 in the age group 60 to 69 years. The annual incidence rate of sigT increased from 4.5 per 10,000 person-years in 2002 to 6.6 per 10,000 person-years in 2011. The 10-year cumulative incidence of sigT was 58.4 cases (95% confidence interval: 57.4 to 59.4) per 10,000 residents. Nearly 324,000 new cases of sigT are expected to occur in England between 2012 and 2021. Conclusions: Tinnitus presents a burden to the health care system that has been rising in recent years. Population-based studies provide crucial underpinning evidence; highlighting the need for further research to address issues around effective diagnosis and clinical management of this heterogeneous condition. PMID:25470370

  9. Clinical outcomes of locked plating of distal femoral fractures in a retrospective cohort

    PubMed Central

    2013-01-01

    Purpose Locked plating (LP) of distal femoral fractures has become very popular. Despite technique suggestions from anecdotal and some early reports, knowledge about risk factors for failure, nonunion (NU), and revision is limited. The purpose of this study was to analyze the complications and clinical outcomes of LP treatment for distal femoral fractures. Materials and methods From two trauma centers, 243 consecutive surgically treated distal femoral fractures (AO/OTA 33) were retrospectively identified. Of these, 111 fractures in 106 patients (53.8% female) underwent locked plate fixation. They had an average age of 54 years (range 18 to 95 years): 34.2% were obese, 18.9% were smokers, and 18.9% were diabetic. Open fractures were present in 40.5% with 79.5% Gustilo type III. Fixation constructs for plate length, working length, and screw concentration were delineated. Nonunion and/or infection, and implant failure were used as outcome complication variables. Outcome was based on surgical method and addressed according to Pritchett for reduction, range of motion, and pain. Results Eighty-three (74.8%) of the fractures healed after the index procedure. Twenty (18.0%) of the patients developed a NU. Four of 20 (20%) resulted in a recalcitrant NU. Length of comminution did not correlate to NU (p = 0.180). Closed injuries had a higher tendency to heal after the index procedure than open injuries (p = 0.057). Closed and minimally open (Gustilo/Anderson types I and II) fractures healed at a significantly higher rate after the index procedure compared to type III open fractures (80.0% versus 61.3%, p = 0.041). Eleven fractures (9.9%) developed hardware failure. Fewer nonunions were found in the submuscular group (10.7%) compared to open reduction (32.0%) (p = 0.023). Fractures above total knee arthroplasties had a significantly greater rate of failed hardware (p = 0.040) and worse clinical outcome according to Pritchett (p = 0.040). Loss of

  10. A longitudinal cohort study of Finnish patients with primary Sjögren's syndrome: clinical, immunological, and epidemiological aspects

    PubMed Central

    Pertovaara, M; Pukkala, E; Laippala, P; Miettinen, A; Pasternack, A

    2001-01-01

    OBJECTIVE—To evaluate outcome in a cohort of Finnish patients with primary Sjögren's syndrome (pSS).
METHODS—Clinical and laboratory data from the time of diagnosis and follow up were collected from 110 patients with pSS (107 women, three men) diagnosed in 1977-1992 in central Finland. The standardised incidence ratio for cancers was determined as the ratio of the observed number of cases to the expected number based on regional population rates. Eighty one of the 93 patients still alive were interviewed, and clinical and laboratory examinations performed in 1994-1997.
RESULTS—The mean (SD) erythrocyte sedimentation rate (33 (22) v 45 (28) mm/1st h), serum IgG (18.8 (7.4) v 22.5 (8.5) g/l), and serum IgM (1.6 (1.1) v 2.0 (1.2) g/l) at the control visit were significantly (p<0.0001) lower than those at baseline. A similar change was observed in a subgroup of patients never treated with glucocorticosteroids or disease modifying antirheumatic drugs. Three non-Hodgkin's lymphomas were diagnosed (standardised incidence ratio 13; 95% confidence interval 2.7 to 38). In a logistic regression model, the patients with pSS with subsequent lymphoma were found to have higher baseline levels of serum β2 microglobulin than the others (odds ratio 1.9; 95% confidence interval 1.1 to 3.4).
CONCLUSION—The results suggest that mean concentrations of serum IgG and IgM in patients with pSS decline with time, possibly reflecting diminishing inflammatory activity. As in previous studies, the incidence of non-Hodgkin's lymphomas in this cohort of patients with pSS was significantly higher than in the reference population.

 PMID:11302868

  11. Clinical Characteristics and Prognostic Significance of TERT Promoter Mutations in Cancer: A Cohort Study and a Meta-Analysis

    PubMed Central

    Yuan, Ping; Cao, Jin-lin; Abuduwufuer, Abudumailamu; Wang, Lu-Ming; Yuan, Xiao-Shuai; Lv, Wang; Hu, Jian

    2016-01-01

    Background The prevalence of telomerase reverse transcriptase (TERT) promoter mutations (pTERTm) in non-small-cell lung cancer (NSCLC) have been investigated, but the results were inconsistent. In addition, several studies have analysed the role of pTERTm in the etiology of various types of cancers, however, the results also remain inconsistent. Methods The genomic DNA sequence of 103 NSCLC samples were analysed to investigate the frequency of pTERTm in these patients and to establish whether these mutations are associated with their clinical data. Furthermore, a meta-analysis based on previously published articles and our cohort study was performed to investigate the association of pTERTm with patient gender, age at diagnosis, metastasis status, tumour stage and cancer prognosis (5-year overall survival rate). Results In the cohort study, 4 patients had C228T and 2 had C250T, with a total mutation frequency up to 5.8%. Significant difference of clinical data between pTERTm carriers and noncarriers was only found in age at diagnosis. In the meta-analysis, We found that pTERTm carriers in cancer patients are older than noncarriers (Mean difference (MD) = 5.24; 95% confidence interval [CI], 2.00 to 8.48), male patients were more likely to harbour pTERTm (odds Ratios (OR) = 1.38; 95% CI, 1.22 to 1.58), and that pTERTm had a significant association with distant metastasis (OR = 3.78; 95% CI, 2.45 to 5.82), a higher tumour grade in patients with glioma (WHO grade III, IV vs. I, II: OR, 2.41; 95% CI, 1.88 to 3.08) and a higher tumour stage in other types of cancer (III, IV vs. I, II: OR, 2.48; 95% CI, 1.48 to 4.15). pTERTm was also significantly associated with a greater risk of death (hazard ratio = 1.71; 95% CI, 1.41 to 2.08). Conclusions pTERTm are a moderately prevalent genetic event in NSCLC. The current meta-analysis indicates that pTERTm is associated with patient age, gender and distant metastasis. It may serves as an adverse prognostic factor in individuals with

  12. Multiple sclerosis: disability and mortality in a cohort of clinically diagnosed patients.

    PubMed

    Citterio, A; Azan, G; Bergamaschi, R; Erbetta, A; Cosi, V

    1989-01-01

    A sample of hospitalized MS patients was selected according to clinical and demographic criteria with the aim of establishing prognostic factors. The sample included 52 patients with first hospitalization from 1 January, 1975, to 31 December, 1976. At follow-up after 12 years a malignant course was observed in 33 patients (death in 13, severe disability in 20 patients). The malignant course was related to age at onset (greater than or equal to 35 years) and higher disability, progressive course and cerebellar symptoms at onset. One half of patients with a relapsing-remitting course entered into a progressive phase of the disease after a mean duration of 7.3 years. PMID:2530458

  13. Carbamoyl phosphate synthetase 1 deficiency in Italy: clinical and genetic findings in a heterogeneous cohort.

    PubMed

    Funghini, S; Thusberg, J; Spada, M; Gasperini, S; Parini, R; Ventura, L; Meli, C; De Cosmo, L; Sibilio, M; Mooney, S D; Guerrini, R; Donati, M A; Morrone, A

    2012-02-10

    Carbamoyl Phosphate Synthetase 1 deficiency (CPS1D) is a rare autosomal recessive urea cycle disorder, potentially leading to lethal hyperammonemia. Based on the age of onset, there are two distinct phenotypes: neonatal and late form. The CPS1 enzyme, located in the mitochondrial matrix of hepatocytes and epithelial cells of intestinal mucosa, is encoded by the CPS1 gene. At present more than 220 clear-cut genetic lesions leading to CPS1D have been reported. As most of them are private mutations diagnosis is complicated. Here we report an overview of the main clinical findings and biochemical and molecular data of 13 CPS1D Italian patients. In two of them, one with the neonatal form and one with the late form, cadaveric auxiliary liver transplant was performed. Mutation analysis in these patients identified 17 genetic lesions, 9 of which were new confirming their "private" nature. Seven of the newly identified mutations were missense/nonsense changes. In order to study their protein level effects, we performed an in silico analysis whose results indicate that the amino acid substitutions occur at evolutionary conserved positions and affect residues necessary for enzyme stability or function. PMID:22173106

  14. A comparison of treatment thresholds in two large Parkinson's disease clinical trial cohorts.

    PubMed

    Marras, Connie; Lang, Anthony E; Eberly, Shirley W; Oakes, David; Fahn, Stanley; Schwid, Steven R; Hyson, Christopher; Shoulson, Ira

    2009-12-15

    Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) and Parkinson Research Examination of CEP-1347 Trial (PRECEPT) were two clinical trials of potential disease-modifying agents for Parkinson's disease that used the time to reaching disability sufficient to require dopaminergic therapy as the primary endpoint. To compare the thresholds for initiating dopaminergic treatment for Parkinson's disease between the two studies, conducted fifteen years apart. Baseline and 12-month endpoint characteristics for subjects in the placebo arms of the two studies were compared. DATATOP placebo subjects had slightly higher total Unified Parkinson's Disease Rating Scale (UPDRS) scores at baseline than PRECEPT placebo subjects (26.1 vs. 23.6, P = 0.03). Time to endpoint was not significantly different. Mean total UPDRS scores at endpoint among those subjects reaching endpoint by 12 months were 48.4 in DATATOP and 37.5 in PRECEPT (P < 0.0001). Baseline disease severity and time to disability requiring dopaminergic therapy were similar in the DATATOP and PRECEPT trials. The threshold for starting dopaminergic treatment was lower in PRECEPT than in the earlier DATATOP study. This may relate to changes in philosophies with respect to starting treatment for Parkinson's disease, but the factors underlying this change remain to be elucidated. PMID:19908310

  15. Visual query tool for finding patient cohorts from a clinical data warehouse of the partners HealthCare system

    PubMed

    Murphy; Barnett; Chueh

    2000-01-01

    The patient base of the Partners HealthCare System in Boston exceeds 1.8 million. Many of these patients are desirable for participation in research studies. To facilitate their discovery, we developed a data warehouse to contain clinical characteristics of these patients. The data warehouse contains diagnosis and procedures from administrative databases. The patients are indexed across institutions and their demographics provided by an Enterprise Master Patient Indexing service. Characteristics of the diagnoses and procedures such as associated providers, dates of service, inpatient/outpatient status, and other visit-related characteristics are also fed from the administrative systems. The targeted users of this system are research clinician s interested in finding patient cohorts for research studies. Their data requirements were analyzed and have been reported elsewhere. We did not expect the clinicians to become expert users of the system. Tools for querying healthcare data have traditionally been text based, although graphical interfaces have been pursued. In order to support the simple drag and drop visual model, as well as the identification and distribution of the patient data, a three-tier software architecture was developed. The user interface was developed in Visual Basic and distributed as an ActiveX object embedded in an HTML page. The middle layer was developed in Java and Microsoft COM. The queries are represented throughout their lifetime as XML objects, and the Microsoft SQL7 database is queried and managed in standard SQL. PMID:11080028

  16. Clinical Phenotypes of Patients with Anti-DFS70/LEDGF Antibodies in a Routine ANA Referral Cohort

    PubMed Central

    Miyara, Makoto; Albesa, Roger; Charuel, Jean-Luc; El Amri, Mohamed; Fritzler, Marvin J.; Ghillani-Dalbin, Pascale; Amoura, Zahir; Musset, Lucile; Mahler, Michael

    2013-01-01

    Objective. To analyze the clinical value of anti-DFS70 antibodies in a cohort of patients undergoing routine antinuclear antibodies (ANAs) testing. Methods. Sera with a dense fine speckled (DFS) indirect immunofluorescence (IIF) pattern from 100 consecutive patients and 100 patients with other IIF patterns were tested for anti-DFS70 antibodies by a novel chemiluminescence immunoassay (CIA) and for ANA by ANA Screen ELISA (both INOVA). Results. Among the 100 patients with a DFS IIF pattern, 91% were anti-DFS70 positive by CIA compared to 3% in the comparator group (P < 0.0001). The CIA and IIF titers of anti-DFS antibodies were highly correlated (rho = 0.89). ANA by ELISA was positive in 35% of patients with the DFS IIF pattern as compared to 67% of patients with other patterns (P < 0.0001). Only 12.0% of patients with DFS pattern and 13.4% with DFS pattern and anti-DFS70 antibodies detected by CIA had systemic autoimmune rheumatic disease (SARD). Only 5/91 (5.5%) patients with anti-DFS70 antibodies had SARD and their sera were negative on the ANA Screen ELISA. Conclusion. Although anti-DFS70 antibodies cannot exclude the presence of SARD, the likelihood is significantly lower than in patients with other IIF patterns and should be included in test algorithms for ANA testing. PMID:23476678

  17. Clinical and Microbiological Profile of a Retrospective Cohort of Enteric Fever in 2 Spanish Tertiary Hospitals

    PubMed Central

    Sánchez-Montalvá, Adrián; Martínez-Pérez, Ángela; Pérez-Molina, José Antonio; González-López, Juan José; Lopez-Vélez, Rogelio; Salvador, Fernando; Sánchez, Irene; Planes, Anna M.; Molina, Israel

    2015-01-01

    Abstract Enteric fever in high-income countries is diagnosed mainly in patients returning from endemic countries. We assess the clinical, microbiological, and prognosis aspects of enteric fever in 2 Spanish tertiary hospitals. A retrospective observational study was conducted at Vall d’Hebron University Hospital and Ramón y Cajal University Hospital in Spain. We reviewed medical records of all patients who were diagnosed with enteric fever from January 2000 to January 2014 at these hospitals. We identified 47 patients with enteric fever episodes. According to their travel history, 35 (74.5%) patients had travelled to highly endemic countries. Imported enteric fever was acquired mainly in Asia (70.3%). Imported infections were implicated in travelers (48.6%), visiting friends and relatives (40%) and immigrants (11.4%). We found that 12 patients were diagnosed with enteric fever without a travel history (autochthonous infection). The resistance profile of the isolates showed decreased ciprofloxacin susceptibility in 66.7% of the imported group and 8.3% of the autochthonous group (P = 0.001). Salmonella strains from patients returning from Asia had an increased risk of having decreased ciprofloxacin susceptibility (odds ratio, 52.25; 95% confidence interval: 8.6–317.7). Patients with imported enteric fever are at higher risk for having a Salmonella strain with decreased ciprofloxacin susceptibility, especially in patients returning from Asia. Initial treatment with third-generation cephalosporin or azithromycin is strongly recommended until a drug-susceptibility test is available. Prevention strategies such as pretravel counseling and immunization before travel may be beneficial. PMID:26020383

  18. Clinical and microbiological profile of a retrospective cohort of enteric fever in 2 Spanish tertiary hospitals.

    PubMed

    Sánchez-Montalvá, Adrián; Martínez-Pérez, Ángela; Pérez-Molina, José Antonio; González-López, Juan José; Lopez-Vélez, Rogelio; Salvador, Fernando; Sánchez, Irene; Planes, Anna M; Molina, Israel

    2015-05-01

    Enteric fever in high-income countries is diagnosed mainly in patients returning from endemic countries. We assess the clinical, microbiological, and prognosis aspects of enteric fever in 2 Spanish tertiary hospitals. A retrospective observational study was conducted at Vall d'Hebron University Hospital and Ramón y Cajal University Hospital in Spain. We reviewed medical records of all patients who were diagnosed with enteric fever from January 2000 to January 2014 at these hospitals. We identified 47 patients with enteric fever episodes. According to their travel history, 35 (74.5%) patients had travelled to highly endemic countries. Imported enteric fever was acquired mainly in Asia (70.3%). Imported infections were implicated in travelers (48.6%), visiting friends and relatives (40%) and immigrants (11.4%). We found that 12 patients were diagnosed with enteric fever without a travel history (autochthonous infection). The resistance profile of the isolates showed decreased ciprofloxacin susceptibility in 66.7% of the imported group and 8.3% of the autochthonous group (P = 0.001). Salmonella strains from patients returning from Asia had an increased risk of having decreased ciprofloxacin susceptibility (odds ratio, 52.25; 95% confidence interval: 8.6-317.7). Patients with imported enteric fever are at higher risk for having a Salmonella strain with decreased ciprofloxacin susceptibility, especially in patients returning from Asia. Initial treatment with third-generation cephalosporin or azithromycin is strongly recommended until a drug-susceptibility test is available. Prevention strategies such as pretravel counseling and immunization before travel may be beneficial. PMID:26020383

  19. Malignant mesothelioma in a cohort of asbestos insulation workers: clinical presentation, diagnosis, and causes of death.

    PubMed Central

    Ribak, J; Lilis, R; Suzuki, Y; Penner, L; Selikoff, I J

    1988-01-01

    Malignant mesothelioma has been rare in the general population. In recent decades its incidence has risen dramatically, parallel to the increasing use of asbestos in industry since 1930. Altogether 17,800 asbestos insulation workers, members of the International Association of Heat and Frost Insulators and Asbestos Workers (AFL-CIO-CLC) in the United States and Canada, were enrolled for prospective study on 1 January 1967 and followed up to the present. Every death that occurs is investigated by our laboratory. One hundred and seventy five deaths from mesothelioma occurred among the 2221 men who died in 1967-76 and 181 more such deaths in the next eight years. Altogether, 356 workers had died of malignant mesothelioma (pleural or peritoneal) by 1984. Diagnosis of mesothelioma was accepted only after all available clinical, radiological, and pathological material was reviewed by our laboratory and histopathological confirmation by the pathology unit made in each case. One hundred and thirty four workers died of pleural and 222 of peritoneal mesothelioma. Age at onset of exposure, age at onset of the disease, and age at death were similar in both groups of patients. Significant difference was noted only in the time elapsed from onset of exposure to the development of first symptoms, which was longer in the group with peritoneal mesothelioma. Shortness of breath, either new or recently increased, and chest pain were the most frequent presenting symptoms in the group with pleural mesothelioma; abdominal pain and distension were frequent in the patients with peritoneal mesothelioma. Pleural effusion or ascites were found in most patients. The most effective approach to the diagnosis of malignant pleural mesothelioma in these cases was by open lung biopsy; exploratory laparotomy was best for diagnosing peritoneal mesothelioma. Patients with pleural mesothelioma died principally from pulmonary insufficiency whereas those with peritoneal mesothelioma succumbed after a

  20. The Danish Collaborative Bacteraemia Network (DACOBAN) database

    PubMed Central

    Gradel, Kim Oren; Schønheyder, Henrik Carl; Arpi, Magnus; Knudsen, Jenny Dahl; Østergaard, Christian; Søgaard, Mette

    2014-01-01

    The Danish Collaborative Bacteraemia Network (DACOBAN) research database includes microbiological data obtained from positive blood cultures from a geographically and demographically well-defined population serviced by three clinical microbiology departments (1.7 million residents, 32% of the Danish population). The database also includes data on comorbidity from the Danish National Patient Registry, vital status from the Danish Civil Registration System, and clinical data on 31% of nonselected records in the database. Use of the unique civil registration number given to all Danish residents enables linkage to additional registries for specific research projects. The DACOBAN database is continuously updated, and it currently comprises 39,292 patients with 49,951 bacteremic episodes from 2000 through 2011. The database is part of an international network of population-based bacteremia registries from five developed countries on three continents. The main purpose of the DACOBAN database is to study surveillance, risk, and prognosis. Sex- and age-specific data on background populations enables the computation of incidence rates. In addition, the high number of patients facilitates studies of rare microorganisms. Thus far, studies on Staphylococcus aureus, enterococci, computer algorithms for the classification of bacteremic episodes, and prognosis and risk in relation to socioeconomic factors have been published. PMID:25258557

  1. 5α-Reductase-2 Deficiency: Clinical Findings, Endocrine Pitfalls, and Genetic Features in a Large Italian Cohort.

    PubMed

    Bertelloni, Silvano; Baldinotti, Fulvia; Russo, Gianni; Ghirri, Paolo; Dati, Eleonora; Michelucci, Angela; Moscuzza, Francesca; Meroni, Silvia; Colombo, Ilaria; Sessa, Maria R; Baroncelli, Giampiero I

    2016-01-01

    Clinical records (n = 24) with an established diagnosis of 5α-reductase-2 deficiency were reviewed. A previous misdiagnosis was present in about 70% (period from first observation to definitive diagnosis: 9.1 ± 10.8 years), and in 8 children gonadal removal was performed before certain diagnosis. Initial sex assignment was female in 16/24 (67%) and male in 8/24 (33%) cases. After diagnosis, sex re-assignment was performed in 5 babies (4 girls to male sex; 1 boy to female sex). Baseline testosterone/DHT ratio was diagnostic in 6/12 subjects (first months of life n = 4; puberty n = 2), while post-hCG testosterone/DHT ratio was diagnostic in all tested individuals (choosing both the cut-off value 15 or 10). Eighteen different mutations in the steroid-5α-reductase-2 (SRD5A2) gene were identified, 5 of which have never been reported. In conclusion, a time lag exists before the diagnosis of 5α-reductase-2 deficiency is established; sex assignment and gonadal removal may be performed before certain diagnosis. Sex re-assignment is usually female to male, but the contrary may occur. A large variability in clinical phenotypes and genetic mutations was present in this cohort. Accurate endocrine evaluation is recommended in babies possibly affected by 5α-reductase-2 deficiency, since the use of appropriate cut-off values of testosterone/DHT ratio after hCG stimulation may permit to select individuals for SRD5A2 gene analysis. A genotype-phenotype correlation was not found in this study. PMID:27070133

  2. The Oxfordshire Community Stroke Project classification system predicts clinical outcomes following intravenous thrombolysis: a prospective cohort study

    PubMed Central

    Yang, Yuling; Wang, Anxin; Zhao, Xingquan; Wang, Chunxue; Liu, Liping; Zheng, Huaguang; Wang, Yongjun; Cao, Yibin; Wang, Yilong

    2016-01-01

    Background The Oxfordshire Community Stroke Project (OCSP) classification system is a simple stroke classification system that can be used to predict clinical outcomes. In this study, we compare the safety and efficacy of intravenous thrombolysis in Chinese stroke patients categorized using the OCSP classification system. Patients and methods We collected data from the Thrombolysis Implementation and Monitoring of Acute Ischemic Stroke in China registry. A total of 1,115 patients treated with intravenous thrombolysis with alteplase within 4.5 hours of stroke onset were included. Symptomatic intracranial hemorrhage (SICH), mortality, and 90-day functional outcomes were compared between the stroke patients with different stroke subtypes. Results Of the 1,115 patients included in the cohort, 197 (17.67%) were classified with total anterior circulation infarct (TACI), 700 (62.78%) with partial anterior circulation infarct, 153 (13.72%) with posterior circulation infarct, and 65 (5.83%) with lacunar infarct. After multivariable adjustment, compared to the patients with non-TACI, those with TACI had a significantly increased risk of SICH (odds ratio [OR] 8.80; 95% confidence interval [CI] 2.84–27.25, P<0.001), higher mortality (OR 5.24; 95% CI 3.19–8.62; P<0.001), and poor functional independence (OR 0.38; 95% CI 0.26–0.56; P<0.001) at 3-month follow-up. Conclusion After thrombolysis, the patients with TACI exhibited greater SICH, a higher mortality rate, and worse 3-month clinical outcomes compared with the patients with non-TACI. The OCSP classification system may help clinicians predict the safety and efficacy of thrombolysis. PMID:27418829

  3. Postoperative complications and clinical outcomes among patients undergoing thoracic and gastrointestinal cancer surgery: A prospective cohort study

    PubMed Central

    Martos-Benítez, Frank Daniel; Gutiérrez-Noyola, Anarelys; Echevarría-Víctores, Adisbel

    2016-01-01

    Objective This study sought to determine the influence of postoperative complications on the clinical outcomes of patients who underwent thoracic and gastrointestinal cancer surgery. Methods A prospective cohort study was conducted regarding 179 consecutive patients who received thorax or digestive tract surgery due to cancer and were admitted to an oncological intensive care unit. The Postoperative Morbidity Survey was used to evaluate the incidence of postoperative complications. The influence of postoperative complications on both mortality and length of hospital stay were also assessed. Results Postoperative complications were found for 54 patients (30.2%); the most common complications were respiratory problems (14.5%), pain (12.9%), cardiovascular problems (11.7%), infectious disease (11.2%), and surgical wounds (10.1%). A multivariate logistic regression found that respiratory complications (OR = 18.68; 95%CI = 5.59 - 62.39; p < 0.0001), cardiovascular problems (OR = 5.06, 95%CI = 1.49 - 17.13; p = 0.009), gastrointestinal problems (OR = 26.09; 95%CI = 6.80 - 100.16; p < 0.0001), infectious diseases (OR = 20.55; 95%CI = 5.99 - 70.56; p < 0.0001) and renal complications (OR = 18.27; 95%CI = 3.88 - 83.35; p < 0.0001) were independently associated with hospital mortality. The occurrence of at least one complication increased the likelihood of remaining hospitalized (log-rank test, p = 0.002). Conclusions Postoperative complications are frequent disorders that are associated with poor clinical outcomes; thus, structural and procedural changes should be implemented to reduce postoperative morbidity and mortality. PMID:27096675

  4. The clinical application of "jetting suture" technique in annular repair under microendoscopic discectomy: A prospective single-cohort observational study.

    PubMed

    Qi, Lei; Li, Mu; Si, Haipeng; Wang, Liang; Jiang, Yunpeng; Zhang, Shuai; Li, Le

    2016-08-01

    To introduce a new designed suture technique in annular repair under the microendoscopic discectomy (MED) surgery and to evaluate the clinical application of the technique in annular repair under MED with at least 2-year follow-up period.A new method of annular repair was designed and named "jetting suture" technique. Thirty consecutive patients with lumbar disc herniation were enrolled in the prospective single-cohort observational study. Patients were followed up at intervals of preoperative, postoperative 1 week, 3 months, 6 months, 1 year, and last follow-up. The clinical outcomes were evaluated by using Japanese Orthopaedic Association (JOA) score, Oswestry Disability Index, and modified Mcnab criteria.The procedure was successfully performed in all cases. No case required conversion to an open procedure. The mean age of patients was 36.6 years. Average blood loss was 45.8 ± 10.2 mL. The preoperative symptoms were alleviated significantly after surgery. All the standardized measures improved significantly at the last follow-up, including JOA score (10.1 to 26.6; P < 0.05) and Oswestry Disability Index (75.3 to 9.6; P < 0.05). Improvement rate of JOA score was 86.4%. Approximately 83.4% of patients reported good or excellent outcomes based on modified Mcnab criteria. No postoperative complication and recurrence of disc herniation was reported.The designed "jetting suture" technique in annular repair under MED can be performed safely and effectively. It could be a viable alternative to annular repair under lumbar discectomy. PMID:27495101

  5. Leprosy Reactions in Patients Coinfected with HIV: Clinical Aspects and Outcomes in Two Comparative Cohorts in the Amazon Region, Brazil

    PubMed Central

    Pires, Carla Andréa Avelar; Jucá Neto, Fernando Octávio Machado; de Albuquerque, Nahima Castelo; Macedo, Geraldo Mariano Moraes; Batista, Keila de Nazaré Madureira; Xavier, Marília Brasil

    2015-01-01

    Background Leprosy, caused by Mycobacterium leprae, can lead to scarring and deformities. Human immunodeficiency virus (HIV), a lymphotropic virus with high rates of replication, leads to cell death in various stages of infection. These diseases have major social and quality of life costs, and although the relevance of their comorbidity is recognized, several aspects are still not fully understood. Methodology/Principal Findings Two cohorts of patients with leprosy in an endemic region of the Amazon were observed. We compared 40 patients with leprosy and HIV (Group 1) and 107 leprosy patients with no comorbidity (Group 2) for a minimum of 2 years. Group 1 predominantly experienced the paucibacillary classification, accounting for 70% of cases, whereas Group 2 primarily experienced the multibacillary classification (80.4% of cases). There was no significant difference in the prevalence of leprosy reactions among the two groups (37.5% for Group 1 vs. 56.1% for Group 2), and the most frequent reaction was Type 1. The appearance of Group 1 patients’ reversal reaction skin lesions was consistent with each clinical form: typically erythematous and infiltrated, with similar progression as those patients without HIV, which responded to prednisone. Patients in both groups primarily experienced a single episode (73.3% in Group 1 and 75% in Group 2), and Group 1 had shorter reaction periods (≤3 months; 93.3%), moderate severity (80%), with 93.3% of the patients in the state of acquired immune deficiency syndrome, and 46.7% presenting the reaction at the time of the immune reconstitution inflammatory syndrome. Conclusions/Significance This study used a large sample and makes a significant contribution to the clinical outcomes of patients in the reactive state with comorbid HIV and leprosy. The data indicate that these diseases, although concurrent, have independent courses. PMID:26029928

  6. A systematic comparison of three commercial estrogen receptor assays in a single clinical outcome breast cancer cohort.

    PubMed

    Kornaga, Elizabeth N; Klimowicz, Alexander C; Guggisberg, Natalia; Ogilvie, Travis; Morris, Don G; Webster, Marc; Magliocco, Anthony M

    2016-08-01

    Breast cancers are routinely assessed for estrogen receptor status using immunohistochemical assays to assist in patient prognosis and clinical management. Specific assays vary between laboratories, and several antibodies have been validated and recommended for clinical use. As numerous factors can influence assay performance, many laboratories have opted for ready-to-use assays using automated stainers to improve reproducibility and consistency. Three commonly used autostainer vendors-Dako, Leica, and Ventana-all offer such estrogen receptor assays; however, they have never been directly compared. Here, we present a systematic comparison of three platform-specific estrogen receptor ready-to-use assays using a retrospective, tamoxifen-treated, breast cancer cohort from patients who were treated in Calgary, Alberta, Canada from 1985 to 2000. We found all assays showed good intra-observer agreement. Inter-observer pathological scoring showed some variability: Ventana had the strongest agreement followed closely by Dako, whereas Leica only showed substantial agreement. We also analyzed each estrogen receptor assay with respect to 5-year disease-free survival, and found that all performed similarly in univariate and multivariate models. Determination of measures of test performance found that the Leica assay had a lower negative predictive value than Dako or Ventana, compared with the original ligand-binding assay, while other measures-sensitivity, specificity, positive predictive value, and accuracy-were comparable between the three ready-to-use assays. When comparing against disease-free survival, the difference in negative predictive value between the vendor assays were not as extreme, but Dako and Ventana still performed slightly better than Leica. Despite some discordance, we found that all ready-to-use assays were comparable with or superior to the ligand-binding assay, endorsing their continued use. Our analysis also allowed for exploration of estrogen receptor

  7. Untreated clinical course of cerebral cavernous malformations: a prospective, population-based cohort study

    PubMed Central

    Salman, Rustam Al-Shahi; Hall, Julie M; Horne, Margaret A; Moultrie, Fiona; Josephson, Colin B; Bhattacharya, Jo J; Counsell, Carl E; Murray, Gordon D; Papanastassiou, Vakis; Ritchie, Vaughn; Roberts, Richard C; Sellar, Robin J; Warlow, Charles P

    2012-01-01

    focal neurological deficit from a CCM is greater than the risk of a first event, is greater for women than for men, and declines over 5 years. This information can be used in clinical practice, but further work is needed to quantify risks precisely in the long term and to understand why women are at greater risk of recurrence than men. Funding UK Medical Research Council, Chief Scientist Office of the Scottish Government, and UK Stroke Association.

  8. Sex differences in disease presentation, treatment and clinical outcomes of patients with hepatocellular carcinoma: a single-centre cohort study

    PubMed Central

    Ladenheim, Maya R; Kim, Nathan G; Nguyen, Pauline; Le, An; Stefanick, Marcia L; Garcia, Gabriel; Nguyen, Mindie H

    2016-01-01

    Background Although sex differences in hepatocellular carcinoma (HCC) risk are well known, it is unclear whether sex differences also exist in clinical presentation and survival outcomes once HCC develops. Methods We performed a retrospective cohort study of 1886 HCC patients seen in a US medical centre in 1998–2015. Data were obtained by chart review with survival data also by National Death Index search. Results The cohort consisted of 1449 male and 437 female patients. At diagnosis, men were significantly younger than women (59.9±10.7 vs 64.0±11.6, p<0.0001). Men had significantly higher rates of tobacco (57.7% vs 31.0%, p<0.001) and alcohol use (63.2% vs 35.1%, p<0.001). Women were more likely to be diagnosed by routine screening versus symptomatically or incidentally (65.5% vs 58.2%, p=0.03) and less likely to present with tumours >5 cm (30.2% vs 39.8%, p=0.001). Surgical and non-surgical treatment utilisation was similar for both sexes. Men and women had no significant difference in median survival from the time of diagnosis (median 30.7 (range=24.5–41.3) vs 33.1 (range=27.4–37.3) months, p=0.84). On multivariate analysis, significant predictors for improved survival included younger age, surgical or non-surgical treatment (vs supportive care), diagnosis by screening, tumour within Milan criteria and lower Model for End-Stage Liver Disease score, but not female sex (adjusted HR=1.01, CI 0.82 to 1.24, p=0.94). Conclusions Although men have much higher risk for HCC development, there were no significant sex differences in disease presentation or survival except for older age and lower tumour burden at diagnosis in women. Female sex was not an independent predictor for survival. PMID:27493763

  9. Cardiovascular events prior to or early after diagnosis of systemic lupus erythematosus in the systemic lupus international collaborating clinics cohort

    PubMed Central

    Urowitz, M B; Gladman, D D; Anderson, N M; Su, J; Romero-Diaz, J; Bae, S C; Fortin, P R; Sanchez-Guerrero, J; Clarke, A; Bernatsky, S; Gordon, C; Hanly, J G; Wallace, D J; Isenberg, D; Rahman, A; Merrill, J; Ginzler, E; Alarcón, G S; Fessler, B F; Petri, M; Bruce, I N; Khamashta, M; Aranow, C; Dooley, M; Manzi, S; Ramsey-Goldman, R; Sturfelt, G; Nived, O; Steinsson, K; Zoma, A; Ruiz-Irastorza, G; Lim, S; Kalunian, K C; Ỉnanç, M; van Vollenhoven, R; Ramos-Casals, M; Kamen, D L; Jacobsen, S; Peschken, C; Askanase, A; Stoll, T

    2016-01-01

    Objective To describe the frequency of myocardial infarction (MI) prior to the diagnosis of systemic lupus erythematosus (SLE) and within the first 2 years of follow-up. Methods The systemic lupus international collaborating clinics (SLICC) atherosclerosis inception cohort enters patients within 15 months of SLE diagnosis. MIs were reported and attributed on a specialised vascular event form. MIs were confirmed by one or more of the following: abnormal ECG, typical or atypical symptoms with ECG abnormalities and elevated enzymes (≥2 times upper limit of normal), or abnormal stress test, echocardiogram, nuclear scan or angiogram. Descriptive statistics were used. Results 31 of 1848 patients who entered the cohort had an MI. Of those, 23 patients had an MI prior to SLE diagnosis or within the first 2 years of disease. Of the 23 patients studied, 60.9% were female, 78.3% were Caucasian, 8.7% black, 8.7% Hispanic and 4.3% other. The mean age at SLE diagnosis was 52.5±15.0 years. Of the 23 MIs that occurred, 16 MIs occurred at a mean of 6.1±7.0 years prior to diagnosis and 7 occurred within the first 2 years of follow-up. Risk factors associated with early MI in univariate analysis are male sex, Caucasian, older age at diagnosis, hypertension, hypercholesterolaemia, family history of MI and smoking. In multivariate analysis only age (OR=1.06 95% CI 1.03 to 1.09), hypertension (OR=5.01, 95% CI 1.38 to 18.23), hypercholesterolaemia (OR=4.43, 95% CI 1.51 to 12.99) and smoking (OR=7.50, 95% CI 2.38 to 23.57) remained significant risk factors. Conclusions In some patients with lupus, MI may develop even before the diagnosis of SLE or shortly thereafter, suggesting that there may be a link between autoimmune inflammation and atherosclerosis. PMID:27099765

  10. The Danish vaccination register.

    PubMed

    Grove Krause, T; Jakobsen, S; Haarh, M; Mølbak, K

    2012-01-01

    Immunisation information systems (IIS) are valuable tools for monitoring vaccination coverage and for estimating vaccine effectiveness and safety. Since 2009, an advanced IIS has been developed in Denmark and will be implemented during 2012–14. This IIS is based on a database existing since 2000. The reporting of all administered vaccinations including vaccinations outside the national programme will become mandatory. Citizens will get access to data about their own vaccinations and healthcare personnel will get access to information on the vaccinations of their patients. A national concept of identification, a national solution combining a personal code and a card with codes, ensures easy and secure access to the register. From the outset, the IIS will include data on childhood vaccinations administered from 1996 and onwards. All Danish citizens have a unique identifier, a so called civil registration number, which allows the linking of information on vaccinations coming from different electronic data sources. The main challenge will be to integrate the IIS with the different electronic patient record systems currently existing at general practitioner, vaccination clinic and hospital level thereby avoiding double-entry. A need has been identified for an updated international classification of vaccine products on the market. Such a classification would also be useful for the future exchange of data on immunisations from IIS between countries. PMID:22551494

  11. Escherichia vulneris in a Danish soccer wound.

    PubMed

    Jepsen, C F; Klebe, T M; Prag, J

    1997-01-01

    Escherichia vulneris was isolated from an infected soccer wound, a finding which has not apparently been described in Europe before, but by questioning Danish clinical microbiological laboratories a further 12 cases were discovered. Treatment with simple debridement and cefuroxime quickly eradicated the bacteria in our case. PMID:9255899

  12. Comparison of Commercial Wrist-Based and Smartphone Accelerometers, Actigraphy, and PSG in a Clinical Cohort of Children and Adolescents

    PubMed Central

    Toon, Elicia; Davey, Margot J.; Hollis, Samantha L.; Nixon, Gillian M.; Horne, Rosemary S.C.; Biggs, Sarah N.

    2016-01-01

    Study Objectives: To compare two commercial sleep devices, an accelerometer worn as a wristband (UP by Jawbone) and a smartphone application (MotionX 24/7), against polysomnography (PSG) and actigraphy (Actiwatch2) in a clinical pediatric sample. Methods: Children and adolescents (n = 78, 65% male, mean age 8.4 ± 4.0 y) with suspected sleep disordered breathing (SDB), simultaneously wore an actiwatch, a commercial wrist-based device and had a smartphone with a sleep application activated placed near their right shoulder, during their diagnostic PSG. Outcome variables were sleep onset latency (SOL), total sleep time (TST), wake after sleep onset (WASO), and sleep efficiency (SE). Paired comparisons were made between PSG, actigraphy, UP, and MotionX 24/7. Epoch-by-epoch comparisons determined sensitivity, specificity, and accuracy between PSG, actigraphy, and UP. Bland-Altman plots determined level of agreement. Differences in bias between SDB severity and developmental age were assessed. Results: No differences in mean TST, WASO, or SE between PSG and actigraphy or PSG and UP were found. Actigraphy overestimated SOL (21 min). MotionX 24/7 underestimated SOL (12 min) and WASO (63 min), and overestimated TST (106 min) and SE (17%). UP showed good sensitivity (0.92) and accuracy (0.86) but poor specificity (0.66) when compared to PSG. Bland-Altman plots showed similar levels of bias in both actigraphy and UP. Bias did not differ by SDB severity, however was affected by age. Conclusions: When compared to PSG, UP was analogous to Actiwatch2 and may have some clinical utility in children with sleep disordered breathing. MotionX 24/7 did not accurately reflect sleep or wake and should be used with caution. Citation: Toon E, Davey MJ, Hollis SL, Nixon GM, Horne RS, Biggs SN. Comparison of commercial wrist-based and smartphone accelerometers, actigraphy, and PSG in a clinical cohort of children and adolescents. J Clin Sleep Med 2016;12(3):343–350. PMID:26446248

  13. Clinical course of sepsis, severe sepsis, and septic shock in a cohort of infected patients from ten Colombian hospitals

    PubMed Central

    2013-01-01

    Background Sepsis has several clinical stages, and mortality rates are different for each stage. Our goal was to establish the evolution and the determinants of the progression of clinical stages, from infection to septic shock, over the first week, as well as their relationship to 7-day and 28-day mortality. Methods This is a secondary analysis of a multicenter cohort of inpatients hospitalized in general wards or intensive care units (ICUs). The general estimating equations (GEE) model was used to estimate the risk of progression and the determinants of stages of infection over the first week. Cox regression with time-dependent covariates and fixed covariates was used to determine the factors related with 7-day and 28-day mortality, respectively. Results In 2681 patients we show that progression to severe sepsis and septic shock increases with intraabdominal and respiratory sources of infection [OR = 1,32; 95%IC = 1,20-1,46 and OR = 1.21, 95%CI = 1,11-1,33 respectively], as well as according to Acute Physiology and Chronic Health Evaluation II (APACHE II) [OR = 1,03; 95%CI = 1,02-1,03] and Sequential Organ Failure Assessment (SOFA) [OR = 1,16; 95%CI = 1,14-1,17] scores. The variables related with first-week mortality were progression to severe sepsis [HR = 2,13; 95%CI = 1,13-4,03] and septic shock [HR = 3,00; 95%CI = 1,50-5.98], respiratory source of infection [HR = 1,76; 95%IC = 1,12-2,77], APACHE II [HR = 1,07; 95% CI = 1,04-1,10] and SOFA [HR = 1,09; 95%IC = 1,04-1,15] scores. Conclusions Intraabdominal and respiratory sources of infection, independently of SOFA and APACHE II scores, increase the risk of clinical progression to more severe stages of sepsis; and these factors, together with progression of the infection itself, are the main determinants of 7-day and 28-day mortality. PMID:23883312

  14. Evidence for the Selective Reporting of Analyses and Discrepancies in Clinical Trials: A Systematic Review of Cohort Studies of Clinical Trials

    PubMed Central

    Dwan, Kerry; Altman, Douglas G.; Clarke, Mike; Gamble, Carrol; Higgins, Julian P. T.; Sterne, Jonathan A. C.; Williamson, Paula R.; Kirkham, Jamie J.

    2014-01-01

    Background Most publications about selective reporting in clinical trials have focussed on outcomes. However, selective reporting of analyses for a given outcome may also affect the validity of findings. If analyses are selected on the basis of the results, reporting bias may occur. The aims of this study were to review and summarise the evidence from empirical cohort studies that assessed discrepant or selective reporting of analyses in randomised controlled trials (RCTs). Methods and Findings A systematic review was conducted and included cohort studies that assessed any aspect of the reporting of analyses of RCTs by comparing different trial documents, e.g., protocol compared to trial report, or different sections within a trial publication. The Cochrane Methodology Register, Medline (Ovid), PsycInfo (Ovid), and PubMed were searched on 5 February 2014. Two authors independently selected studies, performed data extraction, and assessed the methodological quality of the eligible studies. Twenty-two studies (containing 3,140 RCTs) published between 2000 and 2013 were included. Twenty-two studies reported on discrepancies between information given in different sources. Discrepancies were found in statistical analyses (eight studies), composite outcomes (one study), the handling of missing data (three studies), unadjusted versus adjusted analyses (three studies), handling of continuous data (three studies), and subgroup analyses (12 studies). Discrepancy rates varied, ranging from 7% (3/42) to 88% (7/8) in statistical analyses, 46% (36/79) to 82% (23/28) in adjusted versus unadjusted analyses, and 61% (11/18) to 100% (25/25) in subgroup analyses. This review is limited in that none of the included studies investigated the evidence for bias resulting from selective reporting of analyses. It was not possible to combine studies to provide overall summary estimates, and so the results of studies are discussed narratively. Conclusions Discrepancies in analyses between

  15. TNF-alpha antagonist survival rate in a cohort of rheumatoid arthritis patients observed under conditions of standard clinical practice.

    PubMed

    Marchesoni, Antonio; Zaccara, Eleonora; Gorla, Roberto; Bazzani, Chiara; Sarzi-Puttini, Piercarlo; Atzeni, Fabiola; Caporali, Roberto; Bobbio-Pallavicini, Francesca; Favalli, Ennio Giulio

    2009-09-01

    A cohort of rheumatoid arthritis (RA) patients in the Lombardy Rheumatology Network (LOHREN) registry and receiving anti-TNF therapy was evaluated after 6, 12, 24, and 36 months. Of the 1114 patients in the registry 1064 met the clinical criteria for inclusion with 519 receiving infliximab, 303 adalimumab, and 242 etanercept. The therapeutic survival curve of these patients showed that the likelihood of continuing anti-TNF therapy was 78.8% after 12 months, 65.2% after 24 months, and 52.9% after 36 months, with a risk of dropout similar for inefficacy and adverse events. There were 405 anti-TNF therapy discontinuations (38.1%): 180 (16.9%) due to inefficacy, 194 (18.2%) adverse events, and 31 (2.9%) other reasons. Four deaths (2 septicemia, 1 postinfective cerebritis, 1 heart failure) were considered to be related to anti-TNF therapy. Of the discontinuations, 219 (54.1%) occurred within the first 12 months: 110 due to adverse events, 89 inefficacy, and 20 due to other reasons. After 36 months, the likelihood of survival on etanercept (62.5%) was significantly greater than the likelihood of survival on infliximab (49.1%) or adalimumab (53.6%). A higher risk of therapy discontinuations due to adverse events was associated with increasing age, a corticosteroid > 5 mg/day, a high erythrocyte sedimentation rate (ESR), a higher risk of therapy discontinuations due to inefficacy was associated with the previous use of > or = 4 disease-modifying antirheumatic drugs (DMARDs) and a high ESR. Comorbidities, increasing DAS28 values and co-therapy with methotrexate were associated with a lower risk of discontinuation. PMID:19758236

  16. A Global View of the Relationships between the Main Behavioural and Clinical Cardiovascular Risk Factors in the GAZEL Prospective Cohort.

    PubMed

    Meneton, Pierre; Lemogne, Cédric; Herquelot, Eléonore; Bonenfant, Sébastien; Larson, Martin G; Vasan, Ramachandran S; Ménard, Joël; Goldberg, Marcel; Zins, Marie

    2016-01-01

    Although it has been recognized for a long time that the predisposition to cardiovascular diseases (CVD) is determined by many risk factors and despite the common use of algorithms incorporating several of these factors to predict the overall risk, there has yet been no global description of the complex way in which CVD risk factors interact with each other. This is the aim of the present study which investigated all existing relationships between the main CVD risk factors in a well-characterized occupational cohort. Prospective associations between 12 behavioural and clinical risk factors (gender, age, parental history of CVD, non-moderate alcohol consumption, smoking, physical inactivity, obesity, hypertension, dyslipidemia, diabetes, sleep disorder, depression) were systematically tested using Cox regression in 10,736 middle-aged individuals free of CVD at baseline and followed over 20 years. In addition to independently predicting CVD risk (HRs from 1.18 to 1.97 in multivariable models), these factors form a vast network of associations where each factor predicts, and/or is predicted by, several other factors (n = 47 with p<0.05, n = 37 with p<0.01, n = 28 with p<0.001, n = 22 with p<0.0001). Both the number of factors associated with a given factor (1 to 9) and the strength of the associations (HRs from 1.10 to 6.12 in multivariable models) are very variable, suggesting that all the factors do not have the same influence within this network. These results show that there is a remarkably extensive network of relationships between the main CVD risk factors which may have not been sufficiently taken into account, notably in preventive strategies aiming to lower CVD risk. PMID:27598908

  17. Short-term Clinical Outcomes after Transscleral Fixation Using the Intrascleral Pocket Technique: A Retrospective Cohort Study Analysis

    PubMed Central

    Cho, Yong-Wun; Yoo, Woong-Sun; Chung, Inyoung; Seo, Seong-Wook; Yoo, Ji-Myong

    2016-01-01

    Purpose To compare the two transscleral fixation (TSF) techniques of intrascleral pocket and conventional scleral flap with conjunctival division techniques in terms of short-term clinical effects. Methods This retrospective cohort study included all consecutive patients with aphakia in Gyeongsang National University Hospital in Jinju, Korea, who underwent TSF between January 2012 and December 2014. The medical records of all patients were retrospectively reviewed, and the endothelial cell count (ECC), refraction, best-corrected visual acuity (BCVA), intraocular pressure, slit lamp, and fundus examination results before and 1 day and 6 months after surgery were recorded. The postoperative complications and visual outcomes were also recorded. Results The intrascleral pocket and conventional-flap groups did not differ significantly in terms of demographics, presurgical BCVA, or ECC. However, the intrascleral pocket group had a significantly lower BCVA at 1 day and 6 months after surgery compared to the conventional-flap group. The two groups did not differ in terms of ECC 6 months after surgery. The intrascleral pocket group had no postoperative complications, but five patients in the conventional-flap group complained of irritation. In both groups, the intraocular lens was well positioned without tilting or subluxation, and astigmatism was significantly reduced at 1 day and 6 months after surgery. Conclusions The intrascleral pocket technique of TSF does not involve conjunctival dissection and is a successful method of sulcus fixation. It stably corrects the intraocular lens and is easy to perform, which helps to reduce operation time. It also reliably yields rapid visual acuity recovery without complications. PMID:27051258

  18. Analysis of Copy Number Variation in Alzheimer’s Disease in a Cohort of Clinically Characterized and Neuropathologically Verified Individuals

    PubMed Central

    Swaminathan, Shanker; Huentelman, Matthew J.; Corneveaux, Jason J.; Myers, Amanda J.; Faber, Kelley M.; Foroud, Tatiana; Mayeux, Richard; Shen, Li; Kim, Sungeun; Turk, Mari; Hardy, John; Reiman, Eric M.; Saykin, Andrew J.

    2012-01-01

    Copy number variations (CNVs) are genomic regions that have added (duplications) or deleted (deletions) genetic material. They may overlap genes affecting their function and have been shown to be associated with disease. We previously investigated the role of CNVs in late-onset Alzheimer's disease (AD) and mild cognitive impairment using Alzheimer’s Disease Neuroimaging Initiative (ADNI) and National Institute of Aging-Late Onset AD/National Cell Repository for AD (NIA-LOAD/NCRAD) Family Study participants, and identified a number of genes overlapped by CNV calls. To confirm the findings and identify other potential candidate regions, we analyzed array data from a unique cohort of 1617 Caucasian participants (1022 AD cases and 595 controls) who were clinically characterized and whose diagnosis was neuropathologically verified. All DNA samples were extracted from brain tissue. CNV calls were generated and subjected to quality control (QC). 728 cases and 438 controls who passed all QC measures were included in case/control association analyses including candidate gene and genome-wide approaches. Rates of deletions and duplications did not significantly differ between cases and controls. Case-control association identified a number of previously reported regions (CHRFAM7A, RELN and DOPEY2) as well as a new gene (HLA-DRA). Meta-analysis of CHRFAM7A indicated a significant association of the gene with AD and/or MCI risk (P = 0.006, odds ratio = 3.986 (95% confidence interval 1.490–10.667)). A novel APP gene duplication was observed in one case sample. Further investigation of the identified genes in independent and larger samples is warranted. PMID:23227193

  19. Clinical presentation, treatment and outcome of paraphenylene-diamine induced acute kidney injury following hair dye poisoning: a cohort study

    PubMed Central

    Shigidi, Mazin; Mohammed, Osama; Ibrahim, Mohammed; Taha, Elshafie

    2014-01-01

    Introduction In Africa and Asia hair dye is applied together with henna to decorate the hands and feet. Paraphenylene-diamine (PPD), a highly toxic constituent of hair dye can lead to acute kidney injury (AKI). Methods A cohort study was conducted during the period from April 2012 to March 2013 in Khartoum Teaching Hospital, Sudan. It targeted adults presenting acutely with an evident history and clinical features of hair dye poisoning, together with AKI as per the RIFLE criteria. Analysis of data was done using SPSS. Results 30 adults were included, their mean age was 25.6 ± 4.2 years, 93.3% were females. Exposure to PPD was suicidal in 86.7%. The mean duration to onset of renal symptoms was 34.8 ± 7.6 hours, maximum median serum creatinine was 8.6 ± 2.3 mg/dl, 86.7% had loss of kidney function as per the RIFLE classification and required dialysis. Initial renal recovery was seen after a mean duration of 9.8 ± 2.2 days. One patient died, 3.3%; all others, 96.7%, recovered normal kidney function. The amount of ingested PPD correlated significantly to the severity of symptoms, number of dialysis sessions required and time for renal recovery with P values < 0.05. Conclusion Hair dye poisoning was associated with prolonged hospital stay, requirement of dialysis and increased morbidity. The severity of symptoms directly correlates to the dose of PPD ingested, with the kidney damage being reversible in almost all survivors. PMID:25810799

  20. Analysis of copy number variation in Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.

    PubMed

    Swaminathan, Shanker; Huentelman, Matthew J; Corneveaux, Jason J; Myers, Amanda J; Faber, Kelley M; Foroud, Tatiana; Mayeux, Richard; Shen, Li; Kim, Sungeun; Turk, Mari; Hardy, John; Reiman, Eric M; Saykin, Andrew J

    2012-01-01

    Copy number variations (CNVs) are genomic regions that have added (duplications) or deleted (deletions) genetic material. They may overlap genes affecting their function and have been shown to be associated with disease. We previously investigated the role of CNVs in late-onset Alzheimer's disease (AD) and mild cognitive impairment using Alzheimer's Disease Neuroimaging Initiative (ADNI) and National Institute of Aging-Late Onset AD/National Cell Repository for AD (NIA-LOAD/NCRAD) Family Study participants, and identified a number of genes overlapped by CNV calls. To confirm the findings and identify other potential candidate regions, we analyzed array data from a unique cohort of 1617 Caucasian participants (1022 AD cases and 595 controls) who were clinically characterized and whose diagnosis was neuropathologically verified. All DNA samples were extracted from brain tissue. CNV calls were generated and subjected to quality control (QC). 728 cases and 438 controls who passed all QC measures were included in case/control association analyses including candidate gene and genome-wide approaches. Rates of deletions and duplications did not significantly differ between cases and controls. Case-control association identified a number of previously reported regions (CHRFAM7A, RELN and DOPEY2) as well as a new gene (HLA-DRA). Meta-analysis of CHRFAM7A indicated a significant association of the gene with AD and/or MCI risk (P = 0.006, odds ratio = 3.986 (95% confidence interval 1.490-10.667)). A novel APP gene duplication was observed in one case sample. Further investigation of the identified genes in independent and larger samples is warranted. PMID:23227193

  1. The characteristics and clinical outcome of drug-induced liver injury in a Chinese hospital: A retrospective cohort study.

    PubMed

    Chen, Sheng-Sen; Yu, Kang-Kang; Huang, Chong; Li, Ning; Zheng, Jian-Ming; Bao, Su-Xia; Chen, Ming-Quan; Zhang, Wen-Hong

    2016-08-01

    The aim of this cohort study was to determine the characteristics and clinical outcome of 287 patients with drug-induced liver injury (DILI) in a Chinese hospital.Between January 2008 and January 2013, individuals who were diagnosed with DILI were selected. The complete medical records of each case were reviewed, and factors for the outcome of patients with DILI were extracted and analyzed using univariate and multivariate analysis.Two hundred eighty-seven cases identified as DILI were included in the study. A total of 105 different drugs were considered to be related to the hepatotoxicity. The main causative group of drugs was Chinese herb (n = 111). Liver failure developed in 9 (3.1%) patients, and 2 died (0.7%). Overall, complete recovery occurred in 92 (32.1%) patients. Univariate analysis and binary logistic regression analysis identified the digestive symptoms, jaundice, total bilirubin (TBIL), and direct bilirubin (DBIL) as independent factors for the non-recovery of DILI. Then the prediction model, including digestive symptoms, jaundice, TBIL, and DBIL, was built by using binary logistic regression analysis again. Receiver operating characteristic curve validated the strong power (area under the curve (AUC) = 0.907) of prediction model for predicting the DILI non-recovery.DILI is an important cause of liver test abnormalities, and Chinese herb represented the most common drug group. The factors such as digestive symptoms, jaundice, TBIL, and DBIL have effect on DILI outcomes. The prediction model, including digestive symptoms, jaundice, TBIL, and DBIL, established in this study is really an excellent predictive tool for non-recovery of DILI patients. PMID:27559976

  2. Clinical and haematological risk factors for cerebral macrovasculopathy in a sickle cell disease newborn cohort: a prospective study.

    PubMed

    Sommet, Julie; Alberti, Corinne; Couque, Nathalie; Verlhac, Suzanne; Haouari, Zinedine; Mohamed, Damir; François, Martine; Missud, Florence; Holvoet, Laurent; Elmaleh, Monique; Ithier, Ghislaine; Denjean, André; Elion, Jacques; Baruchel, André; Benkerrou, Malika

    2016-03-01

    Children with sickle cell disease (SCD) have a significant vascular morbidity, especially cerebral macrovasculopathy (CV), detectable by transcranial Doppler. This study aimed to identify risk factors for CV using longitudinal biological and clinical data in a SCD newborn cohort followed at the Robert Debre Reference centre (n = 375 SS/Sβ(0) ). Median follow-up was 6·8 years (2677 patient-years). Among the 59 children presenting with CV, seven had a stroke. Overall, the incidence of CV was 2·20/100 patient-years [95% confidence interval (95% CI): 1·64-2·76] and the incidence of stroke was 0·26/100 patient-years (95% CI: 0·07-0·46). The cumulative risk of CV by age 14 years was 26·0% (95% CI: 20·0-33·3%). Risk factors for CV were assessed by a Cox model encompassing linear multivariate modelling of longitudinal quantitative variables. Years per upper-airway obstruction [Hazard ratio (HR) = 1·47; 95% CI: 1·05-2·06] or bronchial obstruction (HR = 1·76; 95% CI: 1·49-2·08) and reticulocyte count (HR = 1·82 per 50 × 10(9) /l increase; 95% CI: 1·10-3·01) were independent risk factors whereas fetal haemoglobin level (HR = 0·68 per 5% increase; 95% CI: 0·48-0·96) was protective. Alpha-thalassaemia was not protective in multivariate analysis (ancillary analysis n = 209). Specific treatment for upper or lower-airway obstruction and indirect targeting of fetal haemoglobin and reticulocyte count by hydroxycarbamide could potentially reduce the risk of CV. PMID:26728571

  3. The return-to-work process of individuals sick-listed because of whiplash-associated disorder: a three-year follow-up study in a Danish cohort of long-term sickness absentees

    PubMed Central

    2014-01-01

    Background The chronic course of whiplash-associated disorder (WAD) has implications for both the individual and society. It has been shown that up to 50% of patients have not yet returned to work six months after a whiplash injury. We wanted to study the return-to-work (RTW) process in individuals sick-listed for more than eight weeks in six Danish municipalities. RTW in individuals sick-listed due to WAD was compared to that in those sick-listed for other musculoskeletal disorders (MSD). Methods Information about long-term sick-listed individuals in six Danish municipalities was retrieved from an existing database. Data on public transfer income were collected and the RTW process was followed on a weekly basis. Multivariate logistic regression analysis of RTW was done four times during the first three years after the start of sick-listing. Results One hundred and four individuals were sick-listed due to WAD and 3,204 individuals were sick-listed due to other MSDs. After 6 months, the RTW was significantly lower in the WAD group. OR for RTW in the WAD group was 0.29 (0.18–0.49) compared to the MSD group. The RTW process for both groups stabilised after two years of follow-up; 44% returned to work in the WAD group as compared to 58% in the MSD group. Conclusion Sick-listed individuals with whiplash-associated disorder are less likely to return to work than individuals who are sick-listed because of other musculoskeletal disorders. In both groups, RTW stabilised after two years of follow-up. PMID:24495801

  4. The Epidemiology, Virology and Clinical Findings of Dengue Virus Infections in a Cohort of Indonesian Adults in Western Java

    PubMed Central

    Kosasih, Herman; Alisjahbana, Bachti; Nurhayati; de Mast, Quirijn; Rudiman, Irani F.; Widjaja, Susana; Antonjaya, Ungke; Novriani, Harli; Susanto, Nugroho H.; Jusuf, Hadi; van der Ven, Andre; Beckett, Charmagne G.; Blair, Patrick J.; Burgess, Timothy H.; Williams, Maya; Porter, Kevin R.

    2016-01-01

    Background Dengue has emerged as one of the most important infectious diseases in the last five decades. Evidence indicates the expansion of dengue virus endemic areas and consequently the exponential increase of dengue virus infections across the subtropics. The clinical manifestations of dengue virus infection include sudden fever, rash, headache, myalgia and in more serious cases, spontaneous bleeding. These manifestations occur in children as well as in adults. Defining the epidemiology of dengue in a given area is critical to understanding the disease and devising effective public health strategies. Methodology/Principal Findings Here, we report the results from a prospective cohort study of 4380 adults in West Java, Indonesia, from 2000–2004 and 2006–2009. A total of 2167 febrile episodes were documented and dengue virus infections were confirmed by RT-PCR or serology in 268 cases (12.4%). The proportion ranged from 7.6 to 41.8% each year. The overall incidence rate of symptomatic dengue virus infections was 17.3 cases/1,000 person years and between September 2006 and April 2008 asymptomatic infections were 2.6 times more frequent than symptomatic infections. According to the 1997 WHO classification guidelines, there were 210 dengue fever cases, 53 dengue hemorrhagic fever cases (including one dengue shock syndrome case) and five unclassified cases. Evidence for sequential dengue virus infections was seen in six subjects. All four dengue virus serotypes circulated most years. Inapparent dengue virus infections were predominantly associated with DENV-4 infections. Conclusions/Significance Dengue virus was responsible for a significant percentage of febrile illnesses in an adult population in West Java, Indonesia, and this percentage varied from year to year. The observed incidence rate during the study period was 43 times higher than the reported national or provincial rates during the same time period. A wide range of clinical severity was observed with

  5. Clinical outcomes of first-line antiretroviral therapy in Latin America: analysis from the LATINA retrospective cohort study.

    PubMed

    Angriman, Federico; Belloso, Waldo H; Sierra-Madero, Juan; Sánchez, Jorge; Moreira, Ronaldo Ismerio; Kovalevski, Leandro O; Orellana, Liliana C; Cardoso, Sandra Wagner; Crabtree-Ramirez, Brenda; La Rosa, Alberto; Losso, Marcelo H

    2016-02-01

    Nearly 2 million people are infected with human immunodeficiency virus (HIV) in Latin America. However, information regarding population-scale outcomes from a regional perspective is scarce. We aimed to describe the baseline characteristics and therapeutic outcomes of newly-treated individuals with HIV infection in Latin America. A Retrospective cohort study was undertaken. The primary explanatory variable was combination antiretroviral therapy based on either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). The main outcome was defined as the composite of all-cause mortality and the occurrence of an AIDS-defining clinical event or a serious non-AIDS-defining event during the first year of therapy. The secondary outcomes included the time to a change in treatment strategy. All analyses were performed according to the intention to treat principle. A total of 937 treatment-naive patients from four participating countries were included (228 patients with PI therapy and 709 with NNRTI-based treatment). At the time of treatment initiation, the patients had a mean age of 37 (SD: 10) years and a median CD4 + T-cell count of 133 cells/mm(3) (interquartile range: 47.5-216.0). Patients receiving PI-based regimens had a significantly lower CD4 + count, a higher AIDS prevalence at baseline and a shorter time from HIV diagnosis until the initiation of treatment. There was no difference in the hazard ratio for the primary outcome between groups. The only covariates associated with the latter were CD4 + cell count at baseline, study site and age. The estimated hazard ratio for the time to a change in treatment (NNRTI vs PI) was 0.61 (95% CI 0.47-0.80, p < 0.01). This study concluded that patients living with HIV in Latin America present with similar clinical outcomes regardless of the choice of initial therapy. Patients treated with PIs are more likely to require a treatment change during the first year of follow up. PMID:25740759

  6. Antibiotic use and clinical outcomes in the acute setting under management by an infectious diseases acute physician versus other clinical teams: a cohort study

    PubMed Central

    Jones, Nicola; Mistry, Vikash; Crook, Derrick; Peto, Tim; Walker, A Sarah

    2016-01-01

    Objectives To assess the magnitude of difference in antibiotic use between clinical teams in the acute setting and assess evidence for any adverse consequences to patient safety or healthcare delivery. Design Prospective cohort study (1 week) and analysis of linked electronic health records (3 years). Setting UK tertiary care centre. Participants All patients admitted sequentially to the acute medical service under an infectious diseases acute physician (IDP) and other medical teams during 1 week in 2013 (n=297), and 3 years 2012–2014 (n=47 585). Primary outcome measure Antibiotic use in days of therapy (DOT): raw group metrics and regression analysis adjusted for case mix. Secondary outcome measures 30-day all-cause mortality, treatment failure and length of stay. Results Antibiotic use was 173 vs 282 DOT/100 admissions in the IDP versus non-IDP group. Using case mix-adjusted zero-inflated Poisson regression, IDP patients were significantly less likely to receive an antibiotic (adjusted OR=0.25 (95% CI 0.07 to 0.84), p=0.03) and received shorter courses (adjusted rate ratio (RR)=0.71 (95% CI 0.54 to 0.93), p=0.01). Clinically stable IDP patients of uncertain diagnosis were more likely to have antibiotics held (87% vs 55%; p=0.02). There was no significant difference in treatment failure or mortality (adjusted p>0.5; also in the 3-year data set), but IDP patients were more likely to be admitted overnight (adjusted OR=3.53 (95% CI 1.24 to 10.03), p=0.03) and have longer length of stay (adjusted RR=1.19 (95% CI 1.05 to 1.36), p=0.007). Conclusions The IDP-led group used 30% less antibiotic therapy with no adverse clinical outcome, suggesting antibiotic use can be reduced safely in the acute setting. This may be achieved in part by holding antibiotics and admitting the patient for observation rather than prescribing, which has implications for costs and hospital occupancy. More information is needed to indicate whether any such longer admission will

  7. Methodology Series Module 1: Cohort Studies

    PubMed Central

    Setia, Maninder Singh

    2016-01-01

    Cohort design is a type of nonexperimental or observational study design. In a cohort study, the participants do not have the outcome of interest to begin with. They are selected based on the exposure status of the individual. They are then followed over time to evaluate for the occurrence of the outcome of interest. Some examples of cohort studies are (1) Framingham Cohort study, (2) Swiss HIV Cohort study, and (3) The Danish Cohort study of psoriasis and depression. These studies may be prospective, retrospective, or a combination of both of these types. Since at the time of entry into the cohort study, the individuals do not have outcome, the temporality between exposure and outcome is well defined in a cohort design. If the exposure is rare, then a cohort design is an efficient method to study the relation between exposure and outcomes. A retrospective cohort study can be completed fast and is relatively inexpensive compared with a prospective cohort study. Follow-up of the study participants is very important in a cohort study, and losses are an important source of bias in these types of studies. These studies are used to estimate the cumulative incidence and incidence rate. One of the main strengths of a cohort study is the longitudinal nature of the data. Some of the variables in the data will be time-varying and some may be time independent. Thus, advanced modeling techniques (such as fixed and random effects models) are useful in analysis of these studies. PMID:26955090

  8. Factors That Affect Quality of Life among People Living with HIV Attending an Urban Clinic in Uganda: A Cohort Study

    PubMed Central

    Mutabazi-Mwesigire, Doris

    2015-01-01

    Introduction With the availability of antiretroviral therapy (ART) and primary general care for people living with HIV (PLHIV) in resource limited settings, PLHIV are living longer, and HIV has been transformed into a chronic illness. People are diagnosed and started on treatment when they are relatively well. Although ART results in clinical improvement, the ultimate goal of treatment is full physical functioning and general well-being, with a focus on quality of life rather than clinical outcomes. However, there has been little research on the relationship of specific factors to quality of life in PLHIV. The objective of this study was to investigate factors associated with quality of life among PLHIV in Uganda receiving basic care and those on ART. Methods We enrolled 1274 patients attending an HIV outpatient clinic into a prospective cohort study. Of these, 640 received ART. All were followed up at 3 and 6 months. Health related quality of life was assessed with the MOS-HIV Health Survey and the Global Person Generated Index (GPGI). Multivariate linear regression and logistic regression with generalized estimating equations were used to examine the relationship of social behavioral and disease factors with Physical Health Summary (PHS) score, Mental Health Summary (MHS) score, and GPGI. Results Among PLHIV receiving basic care, PHS was associated with: sex (p=0.045) - females had lower PHS; age in years at enrollment (p=0.0001) - older patients had lower PHS; and depression (p<0.001) - depressed patients had lower PHS. MHS was only associated with opportunistic infection (p=0.01) - presence of an opportunistic infection was associated with lower MHS. For the GPG the associated variables were age (p=0.03) - older patients had lower GPGI; education (p=0.01) – higher education associated with higher GPGI; and depression - patients with depression had a lower GPGI (p<0.001). Among patients on ART, PHS was associated with: study visit (p=0.01), with increase in

  9. Trends in Clinically Significant Pain Prevalence Among Hospitalized Cancer Patients at an Academic Hospital in Taiwan: A Retrospective Cohort Study.

    PubMed

    Wang, Wei-Yun; Ho, Shung-Tai; Wu, Shang-Liang; Chu, Chi-Ming; Sung, Chun-Sung; Wang, Kwua-Yun; Liang, Chun-Yu

    2016-01-01

    Clinically significant pain (CSP) is one of the most common complaints among cancer patients during repeated hospitalizations, and the prevalence ranges from 24% to 86%. This study aimed to characterize the trends in CSP among cancer patients and examine the differences in the prevalence of CSP across repeated hospitalizations. A hospital-based, retrospective cohort study was conducted at an academic hospital. Patient-reported pain intensity was assessed and recorded in a nursing information system. We examined the differences in the prevalence of worst pain intensity (WPI) and last evaluated pain intensity (LPI) of ≥ 4 or ≥ 7 points among cancer inpatients from the 1st to the 18th hospitalization. Linear mixed models were used to determine the significant difference in the WPI and LPI (≥ 4 or ≥ 7 points) at each hospitalization. We examined 88,133 pain scores from the 1st to the 18th hospitalization among cancer patients. The prevalence of the 4 CSP types showed a trend toward a reduction from the 1st to the 18th hospitalization. There was a robust reduction in the CSP prevalence from the 1st to the 5th hospitalization, except in the case of LPI ≥ 7 points. The prevalence of a WPI ≥ 4 points was significantly higher (0.240-fold increase) during the 1st hospitalization than during the 5th hospitalization. For the 2nd, 3rd, and 4th hospitalizations, there was a significantly higher prevalence of a WPI ≥ 4 points compared with the 5th hospitalization. We also observed significant reductions in the prevalence of a WPI ≥ 7 points during the 1st to the 4th hospitalizations, an LPI ≥ 4 points during the 1st to the 3rd hospitalizations, and an LPI ≥ 7 points during the 1st to the 2nd hospitalization. Although the prevalence of the 4 CSP types decreased gradually, it is impossible to state the causative factors on the basis of this observational and descriptive study. The next step will examine the factors that determine the CSP prevalence among cancer

  10. Sexual and testing behaviour associated with Chlamydia trachomatis infection: a cohort study in an STI clinic in Sweden

    PubMed Central

    Veličko, Inga; Ploner, Alexander; Sparén, Pär; Marions, Lena; Herrmann, Björn; Kühlmann-Berenzon, Sharon

    2016-01-01

    Background Genital chlamydia infection (chlamydia) is the most commonly reported sexually transmitted infection (STI) in Sweden. To guide prevention needs, we aimed to investigate factors associated with chlamydia. Methods A cohort of visitors aged 20–40 years at an urban STI clinic in Sweden was recruited. Behavioural data were collected using a self-administered questionnaire. Self-sampled specimens were tested for chlamydia by a DNA amplification assay. Statistically significant (p<0.05) and epidemiologically relevant covariates were entered in a multivariate Poisson model adjusted for potential confounders (age and gender). Backward stepwise elimination produced a final model. Multiple imputation was used to account for missing values. Results Out of 2814 respondents, 1436 were men with a chlamydia positivity rate of 12.6% vs 8.9% in women. Lifetime testing for chlamydia and HIV was high (82% and 60%, respectively). Factors significantly associated with chlamydia were: 20–24 years old (adjusted risk ratio (ARR)=2.10, 95% CI 1.21 to 3.65); testing reason: contact with a chlamydia case (ARR=6.55, 95% CI 4.77 to 8.98) and having symptoms (ARR=2.19, 95% CI 1.48 to 3.24); 6–10 sexual partners (ARR=1.53, 95% CI 1.06 to 2.21); last sexual activity ‘vaginal sex and oral sex and anal sex and petting’ (ARR=1.84, 95% CI 1.09 to 3.10); alcohol use before sex (ARR=1.98, 95% CI 1.10 to 3.57); men with symptoms (ARR=2.09, 95% CI 1.38 to 3.18); tested for chlamydia (ARR=0.72, 95% CI 0.55 to 0.94). Conclusions Risk factors associated with chlamydia were consistent with previous reports in similar settings and suggest no major changes over time. Increased risk for chlamydia infection associated with high-risk behaviour (eg, alcohol use, increased number of sexual partners) supports the need for behavioural interventions in this population such as promotion of safer sex behaviour (condom use) and testing. PMID:27566631

  11. Derivation and validation of a clinical prediction rule for uncomplicated ureteral stone—the STONE score: retrospective and prospective observational cohort studies

    PubMed Central

    Bomann, Scott; Daniels, Brock; Luty, Seth; Molinaro, Annette; Singh, Dinesh; Gross, Cary P

    2014-01-01

    Objective To derive and validate an objective clinical prediction rule for the presence of uncomplicated ureteral stones in patients eligible for computed tomography (CT). We hypothesized that patients with a high probability of ureteral stones would have a low probability of acutely important alternative findings. Design Retrospective observational derivation cohort; prospective observational validation cohort. Setting Urban tertiary care emergency department and suburban freestanding community emergency department. Participants Adults undergoing non-contrast CT for suspected uncomplicated kidney stone. The derivation cohort comprised a random selection of patients undergoing CT between April 2005 and November 2010 (1040 patients); the validation cohort included consecutive prospectively enrolled patients from May 2011 to January 2013 (491 patients). Main outcome measures In the derivation phase a priori factors potentially related to symptomatic ureteral stone were derived from the medical record blinded to the dictated CT report, which was separately categorized by diagnosis. Multivariate logistic regression was used to determine the top five factors associated with ureteral stone and these were assigned integer points to create a scoring system that was stratified into low, moderate, and high probability of ureteral stone. In the prospective phase this score was observationally derived blinded to CT results and compared with the prevalence of ureteral stone and important alternative causes of symptoms. Results The derivation sample included 1040 records, with five factors found to be most predictive of ureteral stone: male sex, short duration of pain, non-black race, presence of nausea or vomiting, and microscopic hematuria, yielding a score of 0-13 (the STONE score). Prospective validation was performed on 491 participants. In the derivation and validation cohorts ureteral stone was present in, respectively, 8.3% and 9.2% of the low probability (score 0

  12. Strong Association between Serological Status and Probability of Progression to Clinical Visceral Leishmaniasis in Prospective Cohort Studies in India and Nepal

    PubMed Central

    Hasker, Epco; Malaviya, Paritosh; Gidwani, Kamlesh; Picado, Albert; Ostyn, Bart; Kansal, Sangeeta; Singh, Rudra Pratap; Singh, Om Prakash; Chourasia, Ankita; Singh, Abhishek Kumar; Shankar, Ravi; Wilson, Mary E.; Khanal, Basudha; Rijal, Suman; Boelaert, Marleen; Sundar, Shyam

    2014-01-01

    Introduction Asymptomatic persons infected with the parasites causing visceral leishmaniasis (VL) usually outnumber clinically apparent cases by a ratio of 4–10 to 1. We assessed the risk of progression from infection to disease as a function of DAT and rK39 serological titers. Methods We used available data on four cohorts from villages in India and Nepal that are highly endemic for Leishmania donovani. In each cohort two serosurveys had been conducted. Based on results of initial surveys, subjects were classified as seronegative, moderately seropositive or strongly seropositive using both DAT and rK39. Based on the combination of first and second survey results we identified seroconvertors for both markers. Seroconvertors were subdivided in high and low titer convertors. Subjects were followed up for at least one year following the second survey. Incident VL cases were recorded and verified. Results We assessed a total of 32,529 enrolled subjects, for a total follow-up time of 72,169 person years. Altogether 235 incident VL cases were documented. The probability of progression to disease was strongly associated with initial serostatus and with seroconversion; this was particularly the case for those with high titers and most prominently among seroconvertors. For high titer DAT convertors the hazard ratio reached as high as 97.4 when compared to non-convertors. The strengths of the associations varied between cohorts and between markers but similar trends were observed between the four cohorts and the two markers. Discussion There is a strongly increased risk of progressing to disease among DAT and/or rK39 seropositives with high titers. The options for prophylactic treatment for this group merit further investigation, as it could be of clinical benefit if it prevents progression to disease. Prophylactic treatment might also have a public health benefit if it can be corroborated that these asymptomatically infected individuals are infectious for sand flies. PMID

  13. Scaling-Up Access to Antiretroviral Therapy for Children: A Cohort Study Evaluating Care and Treatment at Mobile and Hospital-Affiliated HIV Clinics in Rural Zambia

    PubMed Central

    van Dijk, Janneke H.; Moss, William J.; Hamangaba, Francis; Munsanje, Bornface; Sutcliffe, Catherine G.

    2014-01-01

    Background Travel time and distance are barriers to care for HIV-infected children in rural sub-Saharan Africa. Decentralization of care is one strategy to scale-up access to antiretroviral therapy (ART), but few programs have been evaluated. We compared outcomes for children receiving care in mobile and hospital-affiliated HIV clinics in rural Zambia. Methods Outcomes were measured within an ongoing cohort study of HIV-infected children seeking care at Macha Hospital, Zambia from 2007 to 2012. Children in the outreach clinic group received care from the Macha HIV clinic and transferred to one of three outreach clinics. Children in the hospital-affiliated clinic group received care at Macha HIV clinic and reported Macha Hospital as the nearest healthcare facility. Results Seventy-seven children transferred to the outreach clinics and were included in the analysis. Travel time to the outreach clinics was significantly shorter and fewer caretakers used public transportation, resulting in lower transportation costs and fewer obstacles accessing the clinic. Some caretakers and health care providers reported inferior quality of service provision at the outreach clinics. Sixty-eight children received ART at the outreach clinics and were compared to 41 children in the hospital-affiliated clinic group. At ART initiation, median age, weight-for-age z-scores (WAZ) and CD4+ T-cell percentages were similar for children in the hospital-affiliated and outreach clinic groups. Children in both groups experienced similar increases in WAZ and CD4+ T-cell percentages. Conclusions HIV care and treatment can be effectively delivered to HIV-infected children at rural health centers through mobile ART teams, removing potential barriers to uptake and retention. Outreach teams should be supported to increase access to HIV care and treatment in rural areas. PMID:25122213

  14. Clinical course of light-chain smouldering multiple myeloma (idiopathic Bence Jones proteinuria): a retrospective cohort study

    PubMed Central

    Kyle, Robert A; Larson, Dirk R; Therneau, Terry M; Dispenzieri, Angela; Melton, L Joseph; Benson, Joanne T; Kumar, Shaji; Rajkumar, S Vincent

    2014-01-01

    Summary Background Bence Jones proteinuria is a disorder that is defined by the excretion of monoclonal light-chain protein. About 15–20% of patients with multiple myeloma secrete monoclonal light chains only, without expression of the normal immunoglobulin heavy chain, which constitutes light-chain multiple myeloma. The definition, prevalence, and progression of these premalignant phases of light-chain multiple myeloma have not been fully characterised. We aimed to identify a subset of patients with idiopathic Bence Jones proteinuria who had a high risk of progression to light-chain multiple myeloma analogous to that seen in patients with smouldering multiple myeloma. Methods In this retrospective cohort study, we studied all patients seen at the Mayo Clinic (Rochester, MN, USA) within 30 days of diagnosis of idiopathic Bence Jones proteinuria between Jan 1, 1960, and June 30, 2004. Inclusion criteria were monoclonal light chain in the urine (≥0·2 g/24 h), absence of intact monoclonal immunoglobulin (M protein) in the serum, and no evidence of multiple myeloma, light-chain amyloidosis, or other related plasma-cell proliferative disorders. The primary endpoint was progression to symptomatic multiple myeloma or light-chain amyloidosis. We examined the cumulative probability of progression and the association of potential risk factors on progression rates to identify patients with a high risk of progression to multiple myeloma or light-chain amyloidosis. Findings We identified 101 patients with idiopathic Bence Jones proteinuria. During 901 total person-years of follow-up, 27 (27%) patients developed multiple myeloma and seven (7%) developed light-chain amyloidosis. The major risk factors for progression were amount of urinary excretion of M protein per 24 h, proportion of bone marrow plasma cells, presence of a markedly abnormal free-light-chain ratio (<0·01 or >100), and reduction of all three uninvolved immunoglobulins. Based on the risk of progression

  15. Clinical outcomes of patients requiring ventilatory support in Brazilian intensive care units: a multicenter, prospective, cohort study

    PubMed Central

    2013-01-01

    Introduction Contemporary information on mechanical ventilation (MV) use in emerging countries is limited. Moreover, most epidemiological studies on ventilatory support were carried out before significant developments, such as lung protective ventilation or broader application of non-invasive ventilation (NIV). We aimed to evaluate the clinical characteristics, outcomes and risk factors for hospital mortality and failure of NIV in patients requiring ventilatory support in Brazilian intensive care units (ICU). Methods In a multicenter, prospective, cohort study, a total of 773 adult patients admitted to 45 ICUs over a two-month period requiring invasive ventilation or NIV for more than 24 hours were evaluated. Causes of ventilatory support, prior chronic health status and physiological data were assessed. Multivariate analysis was used to identifiy variables associated with hospital mortality and NIV failure. Results Invasive MV and NIV were used as initial ventilatory support in 622 (80%) and 151 (20%) patients. Failure with subsequent intubation occurred in 54% of NIV patients. The main reasons for ventilatory support were pneumonia (27%), neurologic disorders (19%) and non-pulmonary sepsis (12%). ICU and hospital mortality rates were 34% and 42%. Using the Berlin definition, acute respiratory distress syndrome (ARDS) was diagnosed in 31% of the patients with a hospital mortality of 52%. In the multivariate analysis, age (odds ratio (OR), 1.03; 95% confidence interval (CI), 1.01 to 1.03), comorbidities (OR, 2.30; 95% CI, 1.28 to 3.17), associated organ failures (OR, 1.12; 95% CI, 1.05 to 1.20), moderate (OR, 1.92; 95% CI, 1.10 to 3.35) to severe ARDS (OR, 2.12; 95% CI, 1.01 to 4.41), cumulative fluid balance over the first 72 h of ICU (OR, 2.44; 95% CI, 1.39 to 4.28), higher lactate (OR, 1.78; 95% CI, 1.27 to 2.50), invasive MV (OR, 2.67; 95% CI, 1.32 to 5.39) and NIV failure (OR, 3.95; 95% CI, 1.74 to 8.99) were independently associated with hospital mortality

  16. PRImary care Streptococcal Management (PRISM) study: identifying clinical variables associated with Lancefield group A β-haemolytic streptococci and Lancefield non-Group A streptococcal throat infections from two cohorts of patients presenting with an acute sore throat

    PubMed Central

    Little, Paul; Moore, Michael; Hobbs, F D R; Mant, David; McNulty, Cliodna; Williamson, Ian; Cheng, Edith; Stuart, Beth; Kelly, Joanne; Barnett, Jane; Mullee, Mark

    2013-01-01

    Objective To assess the association between features of acute sore throat and the growth of streptococci from culturing a throat swab. Design Diagnostic cohort. Setting UK general practices. Participants Patients aged 5 or over presenting with an acute sore throat. Patients were recruited for a second cohort (cohort 2, n=517) consecutively after the first (cohort 1, n=606) from similar practices. Main outcome Predictors of the presence of Lancefield A/C/G streptococci. Results The clinical score developed from cohort 1 had poor discrimination in cohort 2 (bootstrapped estimate of area under the receiver operator characteristic (ROC) curve (0.65), due to the poor validity of the individual items in the second data set. Variables significant in multivariate analysis in both cohorts were rapid attendance (prior duration 3 days or less; multivariate adjusted OR 1.92 cohort, 1.67 cohort 2); fever in the last 24 h (1.69, 2.40); and doctor assessment of severity (severely inflamed pharynx/tonsils (2.28, 2.29)). The absence of coryza or cough and purulent tonsils were significant in univariate analysis in both cohorts and in multivariate analysis in one cohort. A five-item score based on Fever, Purulence, Attend rapidly (3 days or less), severely Inflamed tonsils and No cough or coryza (FeverPAIN) had moderate predictive value (bootstrapped area under the ROC curve 0.73 cohort 1, 0.71 cohort 2) and identified a substantial number of participants at low risk of streptococcal infection (38% in cohort 1, 36% in cohort 2 scored ≤1, associated with a streptococcal percentage of 13% and 18%, respectively). A Centor score of ≤1 identified 23% and 26% of participants with streptococcal percentages of 10% and 28%, respectively. Conclusions Items widely used to help identify streptococcal sore throat may not be the most consistent. A modified clinical scoring system (FeverPAIN) which requires further validation may be clinically helpful in identifying individuals who are

  17. Nested Cohort

    Cancer.gov

    NestedCohort is an R software package for fitting Kaplan-Meier and Cox Models to estimate standardized survival and attributable risks for studies where covariates of interest are observed on only a sample of the cohort.

  18. Basic life support knowledge, self-reported skills and fears in Danish high school students and effect of a single 45-min training session run by junior doctors; a prospective cohort study

    PubMed Central

    2014-01-01

    Background Early recognition and immediate bystander cardiopulmonary resuscitation are critical determinants of survival after out-of-hospital cardiac arrest (OHCA). Our aim was to evaluate current knowledge on basic life support (BLS) in Danish high school students and benefits of a single training session run by junior doctors. Methods Six-hundred-fifty-one students were included. They underwent one 45-minute BLS training session including theoretical aspects and hands-on training with mannequins. The students completed a baseline questionnaire before the training session and a follow-up questionnaire one week later. The questionnaire consisted of an eight item multiple-choice test on BLS knowledge, a four-level evaluation of self-assessed BLS skills and evaluation of fear based on a qualitative description and visual analog scale from 0 to 10 for being first responder. Results Sixty-three percent of the students (413/651) had participated in prior BLS training. Only 28% (179/651) knew how to correctly recognize normal breathing. The majority was afraid of exacerbating the condition or causing death by intervening as first responder. The response rate at follow-up was 61% (399/651). There was a significant improvement in correct answers on the multiple-choice test (p < .001). The proportion of students feeling well prepared to perform BLS increased from 30% to 90% (p < .001), and the level of fear of being first responder was decreased 6.8 ± 2.2 to 5.5 ± 2.4 (p < .001). Conclusion Knowledge of key areas of BLS is poor among high school students. One hands-on training session run by junior doctors seems to be efficient to empower the students to be first responders to OHCA. PMID:24731392

  19. Implementation and Operational Research: Engagement in HIV Care Among Persons Enrolled in a Clinical HIV Cohort in Ontario, Canada, 2001–2011

    PubMed Central

    Burchell, Ann N.; Gardner, Sandra; Light, Lucia; Ellis, Brooke M.; Antoniou, Tony; Bacon, Jean; Benoit, Anita; Cooper, Curtis; Kendall, Claire; Loutfy, Mona; McGee, Frank; Raboud, Janet; Rachlis, Anita; Wobeser, Wendy; Rourke, Sean B.

    2015-01-01

    Background: Ensuring that people living with HIV are accessing and staying in care is vital to achieving optimal health outcomes including antiretroviral therapy (ART) success. We sought to characterize engagement in HIV care among participants of a large clinical cohort in Ontario, Canada, from 2001 to 2011. Methods: The Ontario HIV Treatment Network Cohort Study (OCS) is a multisite HIV clinical cohort, which conducts record linkage with the provincial public health laboratory for viral load tests. We estimated the annual proportion meeting criteria for being in care (≥1 viral load per year), in continuous care (≥2 viral load per year ≥90 days apart), on ART, and with suppressed viral load <200 copies per milliliter. Ratios of proportions according to socio-demographic and clinical characteristics were examined using multivariable generalized estimating equations with a log-link. Results: A total of 5380 participants were followed over 44,680 person-years. From 2001 to 2011, we observed high and constant proportions of patients in HIV care (86.3%–88.8%) and in continuous care (76.4%–79.5%). There were statistically significant rises over time in the proportions on ART and with suppressed viral load; by 2011, a majority of patients were on ART (77.3%) and had viral suppression (76.2%). There was minimal variation in HIV engagement indicators by socio-demographic and HIV risk characteristics. Conclusions: In a setting with universal health care, we observed high proportions of HIV care engagement over time and an increased proportion of patients attaining successful virologic suppression, likely due to improvements in ART regimens and changing guidelines. PMID:26322672

  20. Development and validation of a clinical score for prognosis stratification in patients requiring antiretroviral therapy in sub-Saharan Africa: a prospective open cohort study

    PubMed Central

    Gerardo, Rivero; Dayana, Pérez

    2011-01-01

    Background Mortality rates among patients initiating antiretroviral therapy (ART) in sub-Saharan Africa continue high. Also HIV treatment services from the region are affronting the challenges of been attending more patients than never. In this scenario, there are no integrated scoring systems capable of an adequate risk identification/ prognostic stratification among patients requiring ART; in order of optimize actual programmes outcomes. Several independent risk factors at baseline are associated with a poor prognosis after ART initiation. These include: male sex, low body mass index, anemia, low CD4 count and stage-4 WHO disease. The aim of this research was evaluate prospectively a new scoring system composed by these factors. Methods An open cohort study was conducted in 1769 patients from May 2008 to December 2010 at two HIV clinics of Zimbabwe. A new clinical model (MASIB score) was applied at ART initiation and patients were followed for 4 months. After that, validation characteristics of the score were examined. Results Patients selected in this cohort exhibited similar baseline characteristics that the patients selected in previous cohorts from the region. Overall performance for mortality prediction of MASIB score was accurate, as reflected by the Brier score test result 0.084 (95%CI: 0.080–0.088). Calibration was adequate taking in consideration a p>0.05 in the Hosmer Lemeshow test and discrimination was also good (Area Under Curve: 0.915, 95%CI: 0,901– 0,928). Conclusion The new model developed exhibited adequate validation characteristics supporting the clinical use. Further evaluations of this model in others scenarios from the sub-Saharan region are needed. PMID:22187587

  1. A picture is worth a thousand words: maps of HIV indicators to inform research, programs, and policy from NA-ACCORD and CCASAnet clinical cohorts

    PubMed Central

    Althoff, Keri N; Rebeiro, Peter F; Hanna, David B; Padgett, Denis; Horberg, Michael A; Grinsztejn, Beatriz; Abraham, Alison G; Hogg, Robert; Gill, M John; Wolff, Marcelo J; Mayor, Angel; Rachlis, Anita; Williams, Carolyn; Sterling, Timothy R; Kitahata, Mari M; Buchacz, Kate; Thorne, Jennifer E; Cesar, Carina; Cordero, Fernando M; Rourke, Sean B; Sierra-Madero, Juan; Pape, Jean W; Cahn, Pedro; McGowan, Catherine

    2016-01-01

    Introduction Maps are powerful tools for visualization of differences in health indicators by geographical region, but multi-country maps of HIV indicators do not exist, perhaps due to lack of consistent data across countries. Our objective was to create maps of four HIV indicators in North, Central, and South American countries. Methods Using data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) and the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet), we mapped median CD4 at presentation for HIV clinical care, proportion retained in HIV primary care, proportion prescribed antiretroviral therapy (ART), and the proportion with suppressed plasma HIV viral load (VL) from 2010 to 2012 for North, Central, and South America. The 15 Canadian and US clinical cohorts and 7 clinical cohorts in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru represented approximately 2–7% of persons known to be living with HIV in these countries. Results Study populations were selected for each indicator: median CD4 at presentation for care was estimated among 14,811 adults; retention was estimated among 87,979 adults; ART use was estimated among 84,757 adults; and suppressed VL was estimated among 51,118 adults. Only three US states and the District of Columbia had a median CD4 at presentation >350 cells/mm3. Haiti, Mexico, and several states had >85% retention in care; lower (50–74%) retention in care was observed in the US West, South, and Mid-Atlantic, and in Argentina, Brazil, and Peru. ART use was highest (90%) in Mexico. The percentages of patients with suppressed VL in the US South and Northeast were lower than in most of Central and South America. Conclusions These maps provide visualization of gaps in the quality of HIV care and allow for comparison between and within countries as well as monitoring policy and programme goals within geographical boundaries. PMID:27049052

  2. Novel variation and de novo mutation rates in population-wide de novo assembled Danish trios

    PubMed Central

    Besenbacher, Søren; Liu, Siyang; Izarzugaza, José M. G.; Grove, Jakob; Belling, Kirstine; Bork-Jensen, Jette; Huang, Shujia; Als, Thomas D.; Li, Shengting; Yadav, Rachita; Rubio-García, Arcadio; Lescai, Francesco; Demontis, Ditte; Rao, Junhua; Ye, Weijian; Mailund, Thomas; Friborg, Rune M.; Pedersen, Christian N. S.; Xu, Ruiqi; Sun, Jihua; Liu, Hao; Wang, Ou; Cheng, Xiaofang; Flores, David; Rydza, Emil; Rapacki, Kristoffer; Damm Sørensen, John; Chmura, Piotr; Westergaard, David; Dworzynski, Piotr; Sørensen, Thorkild I. A.; Lund, Ole; Hansen, Torben; Xu, Xun; Li, Ning; Bolund, Lars; Pedersen, Oluf; Eiberg, Hans; Krogh, Anders; Børglum, Anders D.; Brunak, Søren; Kristiansen, Karsten; Schierup, Mikkel H.; Wang, Jun; Gupta, Ramneek; Villesen, Palle; Rasmussen, Simon

    2015-01-01

    Building a population-specific catalogue of single nucleotide variants (SNVs), indels and structural variants (SVs) with frequencies, termed a national pan-genome, is critical for further advancing clinical and public health genetics in large cohorts. Here we report a Danish pan-genome obtained from sequencing 10 trios to high depth (50 × ). We report 536k novel SNVs and 283k novel short indels from mapping approaches and develop a population-wide de novo assembly approach to identify 132k novel indels larger than 10 nucleotides with low false discovery rates. We identify a higher proportion of indels and SVs than previous efforts showing the merits of high coverage and de novo assembly approaches. In addition, we use trio information to identify de novo mutations and use a probabilistic method to provide direct estimates of 1.27e−8 and 1.5e−9 per nucleotide per generation for SNVs and indels, respectively. PMID:25597990

  3. The Clinical Research Center for Depression Study: Baseline Characteristics of a Korean Long-Term Hospital-Based Observational Collaborative Prospective Cohort Study

    PubMed Central

    Kim, Tae-Suk; Jeong, Seung Hee; Kim, Jung-Bum; Lee, Min-Soo; Kim, Jae-Min; Yim, Hyeon-Woo

    2011-01-01

    Objective The Clinical Research Center for Depression (CRESCEND) study is a 9-year observational collaborative prospective cohort study for the clinical outcomes in participants with depressive disorders in Korea. In this study, we examined the baseline characteristics of the depressive participants as the hospital-based cohort. Methods Participants were assessed using various instruments including the Clinical Global Impression scale, 17-item Hamilton Depression Rating Scale (HDRS-17), Hamilton Anxiety Rating Scale, Brief Psychiatric Rating Scale, Social and Occupational Functioning Assessment Scale, Beck Depression Inventory-Second Edition, Scale for Suicide Ideation, and World Health Organization Quality of Life assessment instruments-abbreviated version. Also, personal histories of medical and psychiatric illnesses and the range of socio-epidemiologic and clinical data were collected from each participant. Results One thousand one hundred eighty three participants were recruited from 18 hospitals. The mean age of the participants was 47.9±15.9 year-old, 74.4% were female, 82.9% had been diagnosed of major depressive disorder, 40.9% were experiencing their first depressive episode, and 21.4% had a past history of suicide attempts. The majority (85.3%) of the participants were moderately to severely ill. The average HDRS-17 was 19.8±6.1. Significant gender differences at baseline were shown in age, education, marriage, employment, religion, and first depressive episode. Conclusion The baseline findings in the CRESCEND study showed some different characteristics of depression in Korea, suggesting a possibility of ethnic and cultural factors in depression. PMID:21519530

  4. Manganese Superoxide Dismutase and Breast Cancer Recurrence: A Danish Clinical Registry-Based Case-Control Study, and a Meta-Analysis

    PubMed Central

    Cronin-Fenton, Deirdre P.; Christensen, Mariann; Lash, Timothy L.; Ahern, Thomas P.; Pedersen, Lars; Garne, Jens Peter; Ewertz, Marianne; Autrup, Herman; Sørensen, Henrik T.; Hamilton-Dutoit, Stephen

    2014-01-01

    Background Manganese superoxide dismutase (MnSOD) inhibits oxidative damage and cancer therapy effectiveness. A polymorphism in its encoding gene (SOD2: Val16Ala rs4880) may confer poorer breast cancer survival, but data are inconsistent. We examined the association of SOD2 genotype and breast cancer recurrence (BCR) among patients treated with cyclophosphamide-based chemotherapy (Cyclo). We compared our findings with published studies using meta-analyses. Methods We conducted a population-based case-control study of BCR among women in Jutland, Denmark. Subjects were diagnosed with non-metastatic breast cancer from 1990–2001, received adjuvant Cyclo, and were registered in the Danish Breast Cancer Cooperative Group. We identified 118 patients with BCR and 213 matched breast cancer controls. We genotyped SOD2 and used conditional logistic regression to compute the odds ratio (OR) and associated 95% confidence intervals (95% CI) of BCR. We used random-effects meta-analytic models to evaluate the association of SOD2 polymorphisms and BCR. Results The frequency of the SOD2-Ala allele was 70% in cases versus 71% in controls; 40% versus 44% were heterozygotes, and 30% versus 25% were homozygotes, respectively. Heterozygote and homozygote carriers of the Ala allele had no increased rate of BCR (OR = 1.1, 95%CI = 0.65, 2.0, and OR = 0.87, 95%CI = 0.47, 1.6, respectively). Five studies informed the meta-analytic models; summary estimates associating BCR for homozygote, or any inheritance of the variant Ala allele were 1.18 (95%CI = 0.74, 1.88), and 1.18, (95%CI = 0.91, 1.54), respectively. Conclusion Our findings do not suggest that MnSOD enzymatic activity, as measured by SOD2 genotype, affects rates of BCR among patients treated with Cyclo. PMID:24498107

  5. Metformin and other glucose-lowering drug initiation and rates of community-based antibiotic use and hospital-treated infections in patients with type 2 diabetes: a Danish nationwide population-based cohort study

    PubMed Central

    Petersen, Irene; Sørensen, Henrik T; Thomsen, Reimar W

    2016-01-01

    Objective Data on early risk of infection in patients receiving their first treatment for type 2 diabetes are limited. We examined rates of community-based antibiotic use and hospital-treated infection in initiators of metformin and other glucose-lowering drugs (GLDs). Design Population-based cohort study using medical databases. Setting General practice and hospitals in Denmark. Participants 131 949 patients with type 2 diabetes who initiated pharmacotherapy with a GLD between 2005 and 2012. Exposure Initial GLD used for pharmacotherapy. Main outcome measures We computed rates and adjusted HRs of community-based antibiotic use and hospital-treated infection associated with choice of initial GLD with reference to metformin initiation, using an intention-to-treat approach. Results The rate of community-based antibiotic use was 362 per 1000 patient-years at risk (PYAR) and that for hospital-treated infection was 51 per 1000 PYAR. Compared with metformin, the risk of hospital-treated infection was slightly higher in sulfonylurea initiators (HR 1.12, 95% CI 1.08 to 1.16) and substantially higher in insulin initiators (HR 1.63, 95% CI 1.54 to 1.72) initiators after adjustment for comorbid conditions, comedications and other confounding factors. In contrast, virtually no difference was observed for overall community-based antibiotic use (HR 1.02, 95% CI 1.01 to 1.04, for sulfonylurea initiators; and 1.04, 95% CI 1.01 to 1.07, for insulin initiators). Conclusions Rates of community-based antibiotic treatment and hospitalisation for infection were high in patients receiving their first treatment for type 2 diabetes and differed with the choice of initial GLD used for pharmacotherapy. PMID:27543589

  6. Vomiting and Hyponatremia Are Risk Factors for Worse Clinical Outcomes Among Patients Hospitalized Due to Nonsurgical Abdominal Pain: A Retrospective Cohort Study.

    PubMed

    Goren, Idan; Israel, Ariel; Carmel-Neiderman, Narin N; Kliers, Iris; Gringauz, Irina; Dagan, Amir; Lavi, Bruno; Segal, Omer; Segal, Gad

    2016-04-01

    After initial evaluation in the Emergency Department (ED), many patients complaining of abdominal pain are classified as suffering from nonsurgical abdominal pain (NSAP). Clinical characteristics and risk factors for worse prognosis were not published elsewhere.Characterizing the clinical profile of patients hospitalized due to NSAP and identifying predictor variables for worse clinical outcomes.We made a retrospective cohort analysis of patients hospitalized due to NSAP compared to matched control patients (for age, gender, and Charlson comorbidity index) hospitalized due to other, nonsurgical reasons in a ratio of 1 to 10. We further performed in-group analysis of patients admitted due to NSAP in order to appreciate variables (clinical and laboratory parameters) potentially associated with worse clinical outcomes.Overall 23,584 patients were included, of which 2144 were admitted due to NSAP and 21,440 were matched controls. Patients admitted due to NSAP had overall better clinical outcomes: they had lower rates of in-hospital and 30-days mortality (2.8% vs 5.5% and 7.9% vs 10.4% respectively, P < 0.001 for both comparisons). They also had a significantly shorter length of hospital stay (3.9 vs 6.2 days, P < 0.001). Rates of re-hospitalization within 30-days were not significantly different between study groups. Among patients hospitalized due to NSAP, we found that vomiting or hyponatremia at presentation or during hospital stay were associated with worse clinical outcomes.Compared to patients hospitalized due to other, nonsurgical reasons, the overall prognosis of patients admitted due to NSAP is favorable. The combination of NSAP with vomiting and hyponatremia is associated with worse clinical outcomes. PMID:27057886

  7. A two-stage clinical decision support system for early recognition and stratification of patients with sepsis: an observational cohort study

    PubMed Central

    Lyons, Jason J; Greene, Tracy L; Haley, James M

    2015-01-01

    Objective To examine the diagnostic accuracy of a two-stage clinical decision support system for early recognition and stratification of patients with sepsis. Design Observational cohort study employing a two-stage sepsis clinical decision support to recognise and stratify patients with sepsis. The stage one component was comprised of a cloud-based clinical decision support with 24/7 surveillance to detect patients at risk of sepsis. The cloud-based clinical decision support delivered notifications to the patients’ designated nurse, who then electronically contacted a provider. The second stage component comprised a sepsis screening and stratification form integrated into the patient electronic health record, essentially an evidence-based decision aid, used by providers to assess patients at bedside. Setting Urban, 284 acute bed community hospital in the USA; 16,000 hospitalisations annually. Participants Data on 2620 adult patients were collected retrospectively in 2014 after the clinical decision support was implemented. Main outcome measure ‘Suspected infection’ was the established gold standard to assess clinical decision support clinimetric performance. Results A sepsis alert activated on 417 (16%) of 2620 adult patients hospitalised. Applying ‘suspected infection’ as standard, the patient population characteristics showed 72% sensitivity and 73% positive predictive value. A postalert screening conducted by providers at bedside of 417 patients achieved 81% sensitivity and 94% positive predictive value. Providers documented against 89% patients with an alert activated by clinical decision support and completed 75% of bedside screening and stratification of patients with sepsis within one hour from notification. Conclusion A clinical decision support binary alarm system with cross-checking functionality improves early recognition and facilitates stratification of patients with sepsis. PMID:26688744

  8. Danish auroral science history

    NASA Astrophysics Data System (ADS)

    Stauning, P.

    2011-01-01

    Danish auroral science history begins with the early auroral observations made by the Danish astronomer Tycho Brahe during the years from 1582 to 1601 preceding the Maunder minimum in solar activity. Included are also the brilliant observations made by another astronomer, Ole Rømer, from Copenhagen in 1707, as well as the early auroral observations made from Greenland by missionaries during the 18th and 19th centuries. The relations between auroras and geomagnetic variations were analysed by H. C. Ørsted, who also played a vital role in the development of Danish meteorology that came to include comprehensive auroral observations from Denmark, Iceland and Greenland as well as auroral and geomagnetic research. The very important auroral investigations made by Sophus Tromholt are outlined. His analysis from 1880 of auroral observations from Greenland prepared for the significant contributions from the Danish Meteorological Institute, DMI, (founded in 1872) to the first International Polar Year 1882/83, where an expedition headed by Adam Paulsen was sent to Greenland to conduct auroral and geomagnetic observations. Paulsen's analyses of the collected data gave many important results but also raised many new questions that gave rise to auroral expeditions to Iceland in 1899 to 1900 and to Finland in 1900 to 1901. Among the results from these expeditions were 26 unique paintings of the auroras made by the artist painter, Harald Moltke. The expedition to Finland was headed by Dan la Cour, who later as director of the DMI came to be in charge of the comprehensive international geomagnetic and auroral observations made during the Second International Polar Year in 1932/33. Finally, the article describes the important investigations made by Knud Lassen during, among others, the International Geophysical Year 1957/58 and during the International Quiet Sun Year (IQSY) in 1964/65. With his leadership the auroral and geomagnetic research at DMI reached a high international

  9. Association of teriparatide adherence and persistence with clinical and economic outcomes in Medicare Part D recipients: a retrospective cohort study

    PubMed Central

    2013-01-01

    Background Improper medication adherence is associated with increased morbidity, healthcare costs, and fracture risk among patients with osteoporosis. The objective of this study was to evaluate the healthcare utilization patterns of Medicare Part D beneficiaries newly initiating teriparatide, and to assess the association of medication adherence and persistence with bone fracture. Methods This retrospective cohort study assessed medical and pharmacy claims of 761 Medicare members initiating teriparatide in 2008 and 2009. Baseline characteristics, healthcare use, and healthcare costs 12 and 24 months after teriparatide initiation, were summarized. Adherence, measured by Proportion of Days Covered (PDC), was categorized as high (PDC ≥ 80%), moderate (50% ≥ PDC < 80%), and low (PDC < 50%). Non-persistence was measured as refill gaps in subsequent claims longer than 60 days plus the days of supply from the previous claim. Multivariate logistic regression evaluated the association of adherence and persistence with fracture rates at 12 months. Results Within 12 months of teriparatide initiation, 21% of the cohort was highly-adherent. Low-adherent or non-persistent patients visited the ER more frequently than did their highly-adherent or persistent counterparts (χ2 = 5.01, p < 0.05 and χ2 = 5.84, p < 0.05), and had significantly lower mean pharmacy costs ($4,361 versus $13,472 and $4,757 versus $13,187, p < 0.0001). Furthermore, non-persistent patients had significantly lower total healthcare costs. The healthcare costs of highly-adherent patients were largely pharmacy-related. Similar patterns were observed in the 222 patients who had fractures at 12 months, among whom 89% of fracture-related costs were pharmacy-related. The regression models demonstrated no significant association of adherence or persistence with 12-month fractures. Six months before initiating teriparatide, 50.7% of the cohort had experienced at least 1

  10. The Performance of a Modified Glasgow Blatchford Score in Predicting Clinical Interventions in Patients with Acute Nonvariceal Upper Gastrointestinal Bleeding: A Vietnamese Prospective Multicenter Cohort Study

    PubMed Central

    Quach, Duc Trong; Dao, Ngoi Huu; Dinh, Minh Cao; Nguyen, Chung Huu; Ho, Linh Xuan; Nguyen, Nha-Doan Thi; Le, Quang Dinh; Vo, Cong Minh Hong; Le, Sang Kim; Hiyama, Toru

    2016-01-01

    Background/Aims To compare the performance of a modified Glasgow Blatchford score (mGBS) to the Glasgow Blatchford score (GBS) and the pre-endoscopic Rockall score (RS) in predicting clinical interventions in Vietnamese patients with acute nonvariceal upper gastrointestinal bleeding (AN-VUGIB). Methods A prospective multicenter cohort study was conducted in five tertiary hospitals from May 2013 to February 2014. The mGBS, GBS, and pre-endoscopic RS scores were prospectively calculated for all patients. The accuracy of mGBS was compared with that of GBS and pre-endoscopic RS using area under the receiver operating characteristic curve (AUC). Clinical interventions were defined as blood transfusions, endoscopic or radiological intervention, or surgery. Results There were 395 patients including 128 (32.4%) needing endoscopic treatment, 117 (29.6%) requiring blood transfusion and two (0.5%) needing surgery. In predicting the need for clinical intervention, the mGBS (AUC, 0.707) performed as well as the GBS (AUC, 0.708; p=0.87) and outperformed the pre-endoscopic RS (AUC, 0.594; p<0.001). However, none of these scores effectively excluded the need for endoscopic intervention at a threshold of 0. Conclusions mGBS performed as well as GBS and better than pre-endoscopic RS for predicting clinical interventions in Vietnamese patients with ANVUGIB. PMID:26601829