| 1. |
- Dalin, Frida, 1984-, et al.
(författare)
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Clinical and immunological characteristics of Autoimmune Addison's disease : a nationwide Swedish multicenter study
- 2017
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 379-389
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.
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| 2. |
- Semb, Gunvor, et al.
(författare)
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A Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 1. Planning and management.
- 2017
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Ingår i: Journal of Plastic Surgery and Hand Surgery. - : Taylor & Francis. - 2000-656X .- 2000-6764. ; 51:1, s. 2-13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Longstanding uncertainty surrounds the selection of surgical protocols for the closure of unilateral cleft lip and palate, and randomised trials have only rarely been performed. This paper is an introduction to three randomised trials of primary surgery for children born with complete unilateral cleft lip and palate (UCLP). It presents the protocol developed for the trials in CONSORT format, and describes the management structure that was developed to achieve the long-term engagement and commitment required to complete the project.METHOD: Ten established national or regional cleft centres participated. Lip and soft palate closure at 3-4 months, and hard palate closure at 12 months served as a common method in each trial. Trial 1 compared this with hard palate closure at 36 months. Trial 2 compared it with lip closure at 3-4 months and hard and soft palate closure at 12 months. Trial 3 compared it with lip and hard palate closure at 3-4 months and soft palate closure at 12 months. The primary outcomes were speech and dentofacial development, with a series of perioperative and longer-term secondary outcomes.RESULTS: Recruitment of 448 infants took place over a 9-year period, with 99.8% subsequent retention at 5 years.CONCLUSION: The series of reports that follow this introductory paper include comparisons at age 5 of surgical outcomes, speech outcomes, measures of dentofacial development and appearance, and parental satisfaction. The outcomes recorded and the numbers analysed for each outcome and time point are described in the series.TRIAL REGISTRATION: ISRCTN29932826.
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| 3. |
- Utas, Mats, 1968-, et al.
(författare)
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Introduction : setting the stage
- 2023
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Ingår i: Facilitating researchers in insecure zones. - London : Bloomsbury Academic. - 9781350265653 - 9781350265677 ; , s. 1-24, s. 1-24
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Andersson, Maria, et al.
(författare)
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Coinfection with Enteric Pathogens in East African Children with Acute Gastroenteritis-Associations and Interpretations
- 2018
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Ingår i: American Journal of Tropical Medicine and Hygiene. - : American Society of Tropical Medicine and Hygiene. - 0002-9637 .- 1476-1645. ; 98:6, s. 1566-1570
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Tidskriftsartikel (refereegranskat)abstract
- Enteric coinfections among children in low-income countries are very common, but it is not well known if specific pathogen combinations are associated or have clinical importance. In this analysis, feces samples from children in Rwanda and Zanzibar less than 5 years of age, with (N = 994) or without (N = 324) acute diarrhea, were analyzed by realtime polymerase chain reaction targeting a wide range of pathogens. Associations were investigated by comparing codetection and mono-detection frequencies for all pairwise pathogen combinations. More than one pathogen was detected in 840 samples (65%). A negative association (coinfections being less common than expected from probability) was observed for rotavirus in combination with Shigella, Campylobacter, or norovirus genogroup II, but only in patients, which is statistically expected for agents that independently cause diarrhea. A positive correlation was observed, in both patients and controls, between Ct (threshold cycle) values for certain virulence factor genes in enteropathogenic Escherichia coli (EPEC) (eae and bfpA) and toxin genes in enterotoxigenic E. coli (eltB and estA), allowing estimation of how often these genes were present in the same bacteria. A significant positive association in patients only was observed for Shigella andEPEC-eae, suggesting that this coinfection might interact in a manner that enhances symptoms. Although interaction between pathogens that affect symptoms is rare, this work emphasizes the importance and difference in interpretation of coinfections depending on whether they are positively or negatively associated.
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| 5. |
- Andersson, Maria Eva, et al.
(författare)
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Rapid Clearance and Frequent Reinfection With Enteric Pathogens Among Children With Acute Diarrhea in Zanzibar.
- 2017
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 65:8, s. 1371-1377
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Tidskriftsartikel (refereegranskat)abstract
- Background: Acute infectious gastroenteritis is an important cause of illness and death among children in low-income countries. In addition to rotavirus vaccination, actions to improve nutrition status, sanitation, and water quality are important to reduce enteric infections, which are frequent also among asymptomatic children. The aim of this study was to investigate if the high prevalence of these infections reflects that they often are not cleared properly by the immune response or rather is due to frequent pathogen exposure.Methods: Rectal swabs were collected at time of acute diarrhea and 14 days later from 127 children, aged 2-59 months and living in rural Zanzibar, and were analyzed by real-time polymerase chain reaction targeting multiple pathogens.Results: At baseline, detection rates >20% were found for each of enterotoxigenic Escherichia coli, Shigella, Campylobacter, Cryptosporidium, norovirus GII, and adenovirus. At follow-up, a large proportion of the infections had become cleared (34-100%), or the pathogen load reduced, and this was observed also for agents that were presumably unrelated to diarrhea. Still, the detection frequencies at follow-up were for most agents as high as at baseline, because new infections had been acquired. Neither clearance nor reinfection was associated with moderate malnutrition, which was present in 21% of the children.Conclusions: Children residing in poor socioeconomic conditions, as in Zanzibar, are heavily exposed to enteric pathogens, but capable of rapidly clearing causative and coinfecting pathogens.
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| 6. |
- Ankarberg-Lindgren, Carina, 1963, et al.
(författare)
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Nocturnal application of transdermal estradiol patches produces levels of estradiol that mimic those seen at the onset of spontaneous puberty in girls.
- 2001
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X .- 1945-7197. ; 86:7, s. 3039-44
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Tidskriftsartikel (refereegranskat)abstract
- The objective of pubertal induction in children with hypogonadism is to mimic spontaneous puberty in terms of physical and psychological development. In a clinical observation study, we induced puberty in 15 girls with hyper- or hypogonadotropic hypogonadism using low doses of transdermal estradiol patches attached only during the night and compared the estradiol concentrations obtained with those in healthy girls. Pubertal induction was started between the ages of 12.3 and 18.1 yr. A transdermal matrix patch of 17beta-estradiol (25 microg/24 h; Evorel, Janssen Pharmaceuticals-Cilag) was cut into pieces corresponding to 3.1, 4.2, or 6.2 microg/24 h initially and attached to the buttock. After 4-14 months, the dose was increased gradually. Serum 17beta-estradiol concentrations were measured every 2 h by RIA (detection limit, 6.0 pmol/L; 1.6 pg/mL). The results show that it is possible to mimic the spontaneous levels as well as the diurnal pattern of serum 17beta-estradiol in early puberty, by cutting a transdermal 17beta-estradiol matrix patch and attaching a part of it, corresponding to 0.08-0.12 microg estradiol/kg BW, to the buttock nocturnally. In most of the girls, breast development occurred within 3-6 months of the start of treatment.
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| 7. |
- Elfving, Kristina, et al.
(författare)
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Acute Uncomplicated Febrile Illness in Children Aged 2-59 months in Zanzibar : Aetiologies, Antibiotic Treatment and Outcome
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite the fact that a large proportion of children with fever in Africa present at primary health care facilities, few studies have been designed to specifically study the causes of uncomplicated childhood febrile illness at this level of care, especially in areas like Zanzibar that has recently undergone a dramatic change from high to low malaria transmission.METHODS: We prospectively studied the aetiology of febrile illness in 677 children aged 2-59 months with acute uncomplicated fever managed by IMCI (Integrated Management of Childhood Illness) guidelines in Zanzibar, using point-of-care tests, urine culture, blood-PCR, chest X-ray (CXR) of IMCI-pneumonia classified patients, and multiple quantitative (q)PCR investigations of nasopharyngeal (NPH) (all patients) and rectal (GE) swabs (diarrhoea patients). For comparison, we also performed NPH and GE qPCR analyses in 167 healthy community controls. Final fever diagnoses were retrospectively established based on all clinical and laboratory data. Clinical outcome was assessed during a 14-day follow-up. The utility of IMCI for identifying infections presumed to require antibiotics was evaluated.FINDINGS: NPH-qPCR and GE-qPCR detected ≥1 pathogen in 657/672 (98%) and 153/164 (93%) of patients and 158/166 (95%) and 144/165 (87%) of controls, respectively. Overall, 57% (387/677) had IMCI-pneumonia, but only 12% (42/342) had CXR-confirmed pneumonia. Two patients were positive for Plasmodium falciparum. Respiratory syncytial virus (24.5%), influenza A/B (22.3%), rhinovirus (10.5%) and group-A streptococci (6.4%), CXR-confirmed pneumonia (6.2%), Shigella (4.3%) were the most common viral and bacterial fever diagnoses, respectively. Blood-PCR conducted in a sub-group of patients (n = 83) without defined fever diagnosis was negative for rickettsiae, chikungunya, dengue, Rift Valley fever and West Nile viruses. Antibiotics were prescribed to 500 (74%) patients, but only 152 (22%) had an infection retrospectively considered to require antibiotics. Clinical outcome was generally good. However, two children died. Only 68 (11%) patients remained febrile on day 3 and three of them had verified fever on day 14. An additional 29 (4.5%) children had fever relapse on day 14. Regression analysis determined C-reactive Protein (CRP) as the only independent variable significantly associated with CXR-confirmed pneumonia.CONCLUSIONS: This is the first study on uncomplicated febrile illness in African children that both applied a comprehensive laboratory panel and a healthy control group. A majority of patients had viral respiratory tract infection. Pathogens were frequently detected by qPCR also in asymptomatic children, demonstrating the importance of incorporating controls in fever aetiology studies. The precision of IMCI for identifying infections requiring antibiotics was low.
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| 8. |
- Elfving, Kristina, et al.
(författare)
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Pathogen Clearance and New Respiratory Tract Infections Among Febrile Children in Zanzibar Investigated With Multitargeting Real-Time Polymerase Chain Reaction on Paired Nasopharyngeal Swab Samples
- 2018
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Ingår i: Pediatric Infectious Disease Journal. - : Ovid Technologies (Wolters Kluwer Health). - 0891-3668. ; 37:7, s. 643-648
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Tidskriftsartikel (refereegranskat)abstract
- Background: New molecular methods have revealed frequent and often polymicrobial respiratory infections in children in low-income settings. It is not known whether presence of multiple pathogens is due to prolonged infections or to frequent exposure. The aim of this study was to analyze short-term pathogen clearance from nasopharynx and the rate of new respiratory tract infections in febrile preschool children. Methods: Children (n = 207) with uncomplicated acute febrile illness 2-59 months of age presenting to a health center in Zanzibar, Tanzania, April-July 2011, were included. Paired nasopharyngeal swab samples, collected at enrolment and after 14 days, were analyzed by multiple real-time polymerase chain reaction for Adenovirus, bocavirus, Bordetella pertussis, Chlamydophila pneumoniae, Coronaviruses, Enterovirus, influenza A and B virus, metapneumovirus, measles virus, Mycoplasma pneumoniae, parainfluenza virus, Parechovirus, respiratory syncytial virus and Rhinovirus. An age-matched and geographically matched healthy control group (n = 166) underwent nasopharyngeal sampling on 1 occasion. Results: At baseline, 157/207 (76%) patients had at least 1 pathogen detected, in total 199 infections. At follow-up (day 14), 162/199 (81%) of these infections were not detected, including >95% of the previously detected infections with Enterovirus, influenza A virus, influenza B virus, metapneumovirus or parainfluenza virus. Still 115 (56%) children were positive for at least 1 pathogen at follow-up, of which 95/115 (83%) were not found at baseline. Detection of influenza B on day 14 was significantly associated with fever during follow-up. Conclusion: The results suggest that children with acute febrile illness in Zanzibar rapidly clear respiratory tract infections but frequently acquire new infections within 14 days.
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| 9. |
- Elfving, Kristina, et al.
(författare)
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Pneumococcal concentration and serotype distribution in preschool children with radiologically confirmed pneumonia compared to healthy controls prior to introduction of pneumococcal vaccination in Zanzibar : an observational study
- 2022
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The World Health Organization recommends pneumococcal vaccination (PCV) in the first year of life. We investigated pneumococcal serotypes in children with clinical or radiologically confirmed pneumonia and healthy controls prior to PCV13 vaccine introduction in Zanzibar. Methods: Children (n = 677) with non-severe acute febrile illness aged 2-59 months presenting to a health centre in Zanzibar, Tanzania April-July 2011 were included. Nasopharyngeal swabs collected at enrolment were analysed by real-time PCR to detect and quantify pneumococcal serotypes in patients (n = 648) and in healthy asymptomatic community controls (n = 161). Children with clinical signs of pneumonia according to the Integrated Management of Childhood illness guidelines ( "IMCI pneumonia ") were subjected to a chest-X-ray. Consolidation on chest X-ray was considered "radiological pneumonia ". Results: Pneumococcal DNA was detected in the nasopharynx of 562/809 (69%) children (70% in patients and 64% in healthy controls), with no significant difference in proportions between patients with or without presence of fever, malnutrition, IMCI pneumonia or radiological pneumonia. The mean pneumococcal concentration was similar in children with and without radiological pneumonia (Ct value 26.3 versus 27.0, respectively, p = 0.3115). At least one serotype could be determined in 423 (75%) participants positive for pneumococci of which 33% had multiple serotypes detected. A total of 23 different serotypes were identified. One serotype (19F) was more common in children with fever (86/648, 13%) than in healthy controls (12/161, 7%), (p = 0.043). Logistic regression adjusting for age and gender showed that serotype 9A/V [aOR = 10.9 (CI 2.0-60.0, p = 0.006)] and 14 [aOR = 3.9 (CI 1.4-11.0, p = 0.012)] were associated with radiological pneumonia. The serotypes included in the PCV13 vaccine were found in 376 (89%) of the 423 serotype positive participants. Conclusion: The PCV13 vaccine introduced in 2012 targets a great majority of the identified serotypes. Infections with multiple serotypes are common. PCR-determined concentrations of pneumococci in nasopharynx were not associated with radiologically confirmed pneumonia.
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| 10. |
- Elfving, Kristina, et al.
(författare)
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Real-time PCR threshold cycle (Ct) cut-offs help to identify agents causing acute childhood diarrhea in Zanzibar.
- 2014
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Ingår i: Journal of clinical microbiology. - 1098-660X. ; 52:3, s. 916-923
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Tidskriftsartikel (refereegranskat)abstract
- Molecular assays might improve identification of causes of acute diarrheal disease, but may lead to more frequent detection of asymptomatic infections. In the present study real-time PCR targeting 14 pathogens was applied on rectal swabs from 330 children aged 2-59 months in Zanzibar, 165 with acute diarrhea and 165 asymptomatic controls. At least one pathogen was detected in 94% of patients and 84% of controls, with higher rates in patients for norovirus genogroup II (20% vs. 2.4%, p<0.0001), rotavirus (10% vs. 1.8%, p=0.003) and Cryptosporidium (30% vs. 11%, p<0.0001). Detection rates did not differ significantly for enterotoxigenic Escherichia coli (ETEC)-estA (33% vs. 24%), ETEC-eltB (44% vs. 46%), Shigella (35% vs. 33%), and Campylobacter (35% vs. 33%), but for these agents Ct (threshold cycle) values were lower (pathogen loads were higher) in sick children than in controls. In multivariate analysis, Ct values for norovirus genogroup II, rotavirus, Cryptosporidium, ETEC-estA and Shigella were independently associated with diarrhea. We conclude that this real-time PCR allows convenient detection of essentially all diarrheagenic agents, and provides Ct values that may be critical for interpretation of results for pathogens with similar detection rates in patients and controls. The results indicate that assessment of pathogen load may improve identification of agents causing gastroenteritis in children.
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