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  • Lonnrot, Maria; Lynch, Kristian; Larsson, Helena Elding; Lernmark, Ake; Rewers, Marian; Hagopian, William; She, Jin-Xiong; Simell, Olli; Ziegler, Anette-G; Akolkar, Beena; Krischer, Jeffrey; Hyoty, Heikki; TEDDY Study Grp; Knip, Mikael (2015)
    Background: Early childhood environmental exposures, possibly infections, may be responsible for triggering islet autoimmunity and progression to type 1 diabetes (T1D). The Environmental Determinants of Diabetes in the Young (TEDDY) follows children with increased HLA-related genetic risk for future T1D. TEDDY asks parents to prospectively record the child's infections using a diary book. The present paper shows how these large amounts of partially structured data were reduced into quantitative data-sets and further categorized into system-specific infectious disease episodes. The numbers and frequencies of acute infections and infectious episodes are shown. Methods: Study subjects (n = 3463) included children who had attended study visits every three months from age 3 months to 4 years, without missing two or more consecutive visits during the follow-up. Parents recorded illnesses prospectively in a TEDDY Book at home. The data were entered into the study database during study visits using ICD-10 codes by a research nurse. TEDDY investigators grouped ICD-10 codes and fever reports into infectious disease entities and further arranged them into four main categories of infectious episodes: respiratory, gastrointestinal, other, and unknown febrile episodes. Incidence rate of infections was modeled as function of gender, HLA-DQ genetic risk group and study center using the Poisson regression. Results: A total of 113,884 ICD-10 code reports for infectious diseases recorded in the database were reduced to 71,578 infectious episodes, including 74.0% respiratory, 13.1% gastrointestinal, 5.7% other infectious episodes and 7.2% febrile episodes. Respiratory and gastrointestinal infectious episodes were more frequent during winter. Infectious episode rates peaked at 6 months and began declining after 18 months of age. The overall infectious episode rate was 5.2 episodes per person-year and varied significantly by country of residence, sex and HLA genotype. Conclusions: The data reduction and categorization process developed by TEDDY enables analysis of single infectious agents as well as larger arrays of infectious agents or clinical disease entities. The preliminary descriptive analyses of the incidence of infections among TEDDY participants younger than 4 years fits well with general knowledge of infectious disease epidemiology. This protocol can be used as a template in forthcoming time-dependent TEDDY analyses and in other epidemiological studies.
  • the DIABIMMUNE Study Group; Mustonen, Neea; Siljander, Heli; Peet, Aleksandr; Tillmann, Vallo; Härkönen, Taina; Ilonen, Jorma; Hyöty, Heikki; Knip, Mikael (2019)
    Aim Infections in early childhood are common reasons to seek medical attention. This study compares the prevalence of infections, and the use of antibiotics and antipyretic-analgesics, in children from Finland, Estonia and Russian Karelia. Methods Children with a genetically increased risk for type 1 diabetes (N = 797) were observed from birth up to 3 years of age. Illnesses and medications were reported by parents continuously. All reported infections, antibiotics and antipyretic-analgesics were compared between Finland and Estonia, and to a lesser extent with Russian Karelia, due to poor study compliance. Results Compared with Estonians, Finns reported more infections during the first and second years of life. During the follow-up, Finnish children had 10 infections while Estonians only had 8 (p <0.001). Finns also used more antibiotics and antipyretic-analgesics in each year during the follow-up. Russian Karelians reported the lowest frequency of infections and the most infrequent use of antibiotics and antipyretic-analgesics in the first two years of life. Conclusion Infections and the use of antibiotics and antipyretic-analgesics in early childhood were most frequent in Finland, where socio-economic conditions are the most developed and microbial encounters are sparse. This may reflect on the hygiene hypothesis, a less effective immune system that allows normally harmless microbes to attack and cause clinical infections.
  • Hemilä, Harri; Virtamo, Jarmo; Albanes, Demetrius; Kaprio, Jaakko (2003)
  • Katila, Maija; Saarenpää-Heikkilä, Outi; Saha, Marja-Terttu; Vuorela, Nina; Huhtala, Heini; Korhonen, Laura S.; Lukkarinen, Minna; Tuulari, Jetro J.; Karlsson, Linnea; Karlsson, Hasse; Paavonen, E. Juulia (2021)
    Objectives: To evaluate the prevalence and persistence of snoring during the first two years of life in two Finnish birth cohorts and to assess the associated factors. Study design: The study population comprised 947 children from the CHILD-SLEEP (CS) and 1393 children from the FinnBrain (FB) birth cohorts. Questionnaires were provided to both parents when the child was 24 months of age. The questionnaire consisted of parts concerning the child's sleep and environmental factors. Results: The combined prevalence of habitual snoring in the two birth cohorts at the age of 24 months was 2.3% (95% CI 1.5-3.1), which is markedly lower than reported previously. Children suffering from recurrent infections (CS odds ratio (OR) 3.9, 95% CI 1.2-12.5) or asthma (FB OR 4.3, 1.4-13.5) snored habitually more often. Both the mother's (CS OR 3.2, 1.2-9.0) and father's (CS OR 3.4, 1.4-8.0) snoring every night added to the risk of the child snoring. In the multivariate models, parental snoring (CS adjusted odds ratio (ORa) 2.8, 1.1-6.8), the mother's lower level of education (CS ORa 2.9, 1.2-7.5, FB ORa 2.1, 1.0-4.5), and the mother's lower monthly income (FB ORa 2.9, 1.3-6.3) associated with the child's habitual snoring. Conclusions: The prevalence of habitual snoring in two Finnish birth cohorts is lower than reported previously. The independent risk factors for habitual snoring at the age of two years were the parents' snoring and the mother's low income and low education. (C) 2021 The Authors. Published by Elsevier B.V.
  • Raudasoja, Aleksi J.; Falkenbach, Petra; Vernooij, Robin W. M.; Mustonen, Jussi M. J.; Agarwal, Arnav; Aoki, Yoshitaka; Blanker, Marco H.; Cartwright, Rufus; Garcia-Perdomo, Herney A.; Kilpelainen, Tuomas P.; Lainiala, Olli; Lamberg, Tiina; Nevalainen, Olli P. O.; Raittio, Eero; Richard, Patrick O.; Violette, Philippe D.; Komulainen, Jorma; Sipila, Raija; Tikkinen, Kari A. O. (2022)
    Background: Healthcare costs are rising, and a substantial proportion of medical care is of little value. De-implementation of low-value practices is important for improving overall health outcomes and reducing costs. We aimed to identify and synthesize randomized controlled trials (RCTs) on de-implementation interventions and to provide guidance to improve future research. Methods: MEDLINE and Scopus up to May 24, 2021, for individual and cluster RCTs comparing de-implementation interventions to usual care, another intervention, or placebo. We applied independent duplicate assessment of eligibility, study characteristics, outcomes, intervention categories, implementation theories, and risk of bias. Results: Of the 227 eligible trials, 145 (64%) were cluster randomized trials (median 24 clusters; median follow-up time 305 days), and 82 (36%) were individually randomized trials (median follow-up time 274 days). Of the trials, 118 (52%) were published after 2010, 149 (66%) were conducted in a primary care setting, 163 (72%) aimed to reduce the use of drug treatment, 194 (85%) measured the total volume of care, and 64 (28%) low-value care use as outcomes. Of the trials, 48 (21%) described a theoretical basis for the intervention, and 40 (18%) had the study tailored by context-specific factors. Of the de-implementation interventions, 193 (85%) were targeted at physicians, 115 (51%) tested educational sessions, and 152 (67%) multicomponent interventions. Missing data led to high risk of bias in 137 (60%) trials, followed by baseline imbalances in 99 (44%), and deficiencies in allocation concealment in 56 (25%). Conclusions: De-implementation trials were mainly conducted in primary care and typically aimed to reduce low-value drug treatments. Limitations of current de-implementation research may have led to unreliable effect estimates and decreased clinical applicability of studied de-implementation strategies. We identified potential research gaps, including de-implementation in secondary and tertiary care settings, and interventions targeted at other than physicians. Future trials could be improved by favoring simpler intervention designs, better control of potential confounders, larger number of clusters in cluster trials, considering context-specific factors when planning the intervention (tailoring), and using a theoretical basis in intervention design. Registration: OSF Open Science Framework hk4b2.
  • Vuori-Holopainen, Elina; Peltola, Heikki (2001)
    Identification of the etiology of childhood pneumonia is difficult, even in the cases that most likely have bacterial origins. A positive blood culture result is diagnostic but rare (50% of cases (virological tests were rarely done); (2) lung tap is safer than is generally considered; (3) potential pneumothorax is mostly symptomless and resolves spontaneously without impairing recovery; and (4) in comparison with routine diagnostic tools, lung tap offers so many advantages that it warrants reconsideration at centers where personnel have experience in handling potential pneumothorax.
  • Hemilä, Harri; Virtamo, Jarmo; Albanes, Demetrius; Kaprio, Jaakko (2006)
  • Viitanen, Sanna Johanna; Lappalainen, Anu Katriina; Christensen, M. B.; Sankari, Satu Marja; Rajamäki, Minna (2017)
    BACKGROUND: Acute-phase proteins (APPs) are sensitive markers of inflammation, and serum C-reactive protein (CRP) recently has been shown to be a useful diagnostic marker in dogs with bacterial pneumonia (BP). In humans with community-acquired pneumonia, APPs also have great utility as follow-up markers aiding in the assessment of treatment response. OBJECTIVES: The aim of our study was to investigate the applicability of APPs as markers of treatment response in dogs with BP. ANIMALS: Nineteen dogs diagnosed with BP and 64 healthy dogs. METHODS: The study was conducted as a prospective longitudinal observational study. Serum CRP, serum amyloid A (SAA), and haptoglobin concentrations were followed during a natural course of BP. Normalization of serum CRP was used to guide the duration of antibiotic treatment (treatment was stopped 5-7 days after CRP normalized) in 8 of 17 dogs surviving to discharge; 9 of 17 dogs were treated according to conventional recommendations. RESULTS: All measured APPs initially were significantly increased, but the magnitude of increase was not correlated to disease severity. C-reactive protein and SAA concentrations decreased rapidly after initiation of antimicrobial treatment. When normalization of serum CRP was used to guide the duration of antibiotic treatment, treatment duration was significantly (P = .015) decreased without increasing the number of relapses. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum CRP and SAA reflected the recovery process well and therefore may be used as markers of treatment response. According to the results, the normalization of serum CRP may be used to guide the duration of antibiotic treatment in dogs with BP.
  • Hemilä, Harri; Chalker, Elizabeth (2013)
    BACKGROUND: Vitamin C (ascorbic acid) for preventing and treating the common cold has been a subject of controversy for 70 years. OBJECTIVES: To find out whether vitamin C reduces the incidence, the duration or severity of the common cold when used either as a continuous regular supplementation every day or as a therapy at the onset of cold symptoms. SEARCH METHODS: We searched CENTRAL 2012, Issue 11, MEDLINE (1966 to November week 3, 2012), EMBASE (1990 to November 2012), CINAHL (January 2010 to November 2012), LILACS (January 2010 to November 2012) and Web of Science (January 2010 to November 2012). We also searched the U.S. National Institutes of Health trials register and WHO ICTRP on 29 November 2012. SELECTION CRITERIA: We excluded trials which used less than 0.2 g per day of vitamin C and trials without a placebo comparison. We restricted our review to placebo-controlled trials. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. We assessed 'incidence' of colds during regular supplementation as the proportion of participants experiencing one or more colds during the study period. 'Duration' was the mean number of days of illness of cold episodes. MAIN RESULTS: Twenty-nine trial comparisons involving 11,306 participants contributed to the meta-analysis on the risk ratio (RR) of developing a cold whilst taking vitamin C regularly over the study period. In the general community trials involving 10,708 participants, the pooled RR was 0.97 (95% confidence interval (CI) 0.94 to 1.00). Five trials involving a total of 598 marathon runners, skiers and soldiers on subarctic exercises yielded a pooled RR of 0.48 (95% CI 0.35 to 0.64).Thirty-one comparisons examined the effect of regular vitamin C on common cold duration (9745 episodes). In adults the duration of colds was reduced by 8% (3% to 12%) and in children by 14% (7% to 21%). In children, 1 to 2 g/day vitamin C shortened colds by 18%. The severity of colds was also reduced by regular vitamin C administration.Seven comparisons examined the effect of therapeutic vitamin C (3249 episodes). No consistent effect of vitamin C was seen on the duration or severity of colds in the therapeutic trials.The majority of included trials were randomised, double-blind trials. The exclusion of trials that were either not randomised or not double-blind had no effect on the conclusions. AUTHORS' CONCLUSIONS: The failure of vitamin C supplementation to reduce the incidence of colds in the general population indicates that routine vitamin C supplementation is not justified, yet vitamin C may be useful for people exposed to brief periods of severe physical exercise. Regular supplementation trials have shown that vitamin C reduces the duration of colds, but this was not replicated in the few therapeutic trials that have been carried out. Nevertheless, given the consistent effect of vitamin C on the duration and severity of colds in the regular supplementation studies, and the low cost and safety, it may be worthwhile for common cold patients to test on an individual basis whether therapeutic vitamin C is beneficial for them. Further therapeutic RCTs are warranted.
  • Hemila, Harri (2016)
    Background: Vitamin E has influenced the immune system in laboratory studies. Dozens of animal experiments have found that vitamin E offered protection against infections caused by viruses and bacteria. Previously, significant heterogeneity was found in the effect of vitamin E supplementation on pneumonia in humans. The aim of this study was to examine how the effect of vitamin E on pneumonia risk depends on age. Methods: Secondary analysis of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention study in Finland, 1985-1993, was performed. Participants were male smokers aged 50-69 years at the baseline who started to smoke at >= 21 years (N=7,469). Intervention was 50 mg/d of vitamin E for 5-8 years. The outcome was the incidence of hospital-treated, community-acquired pneumonia by the age at the follow-up. Results: Among 2,216 participants who smoked 5-19 cigarettes per day at baseline and exercised at leisure time, vitamin E supplementation reduced the incidence of pneumonia by 69% (95% confidence interval [CI]: 43%-83%; 57 pneumonia cases). In this subgroup, vitamin E prevented pneumonia in 12.9% of participants by the age of 74 years. Among 5,253 participants who smoked >= 20 cigarettes per day at baseline or did not exercise, the incidence of pneumonia was 14% lower in the vitamin E participants (95% CI: -38% to +21%; 139 cases). One-third of the participants quit smoking for a period, of whom 27 got pneumonia. The incidence of pneumonia was 72% (95% CI: 31%-89%) lower in the vitamin E group, and this benefit was also seen among those males who smoked >20 cigarettes per day at baseline or did not exercise. Conclusion: Although the evidence of benefit from vitamin E against pneumonia in elderly males is strong in this analysis, the overall findings about vitamin E have been complex. Further research on vitamin E in nonsmoking elderly males is warranted.
  • Hemila, Harri (2016)
    Analyses in nutritional epidemiology usually assume a uniform effect of a nutrient. Previously, four subgroups of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of Finnish male smokers aged 50-69 years were identified in which vitamin E supplementation either significantly increased or decreased the risk of pneumonia. The purpose of this present study was to quantify the level of true heterogeneity in the effect of vitamin E on pneumonia incidence using the I-2 statistic. The I-2 value estimates the percentage of total variation across studies that is explained by true differences in the treatment effect rather than by chance, with a range from 0 to 100 %. The I-2 statistic for the effect of vitamin E supplementation on pneumonia risk for five subgroups of the ATBC population was 89% (95% CI 78, 95 %), indicating that essentially all heterogeneity was true variation in vitamin E effect instead of chance variation. The I-2 statistic for heterogeneity in vitamin E effects on pneumonia risk was 92% (95% CI 80, 97 %) for three other ATBC subgroups defined by smoking level and leisure-time exercise level. Vitamin E decreased pneumonia risk by 69% among participants who had the least exposure to smoking and exercised during leisure time (7.6% of the ATBC participants), and vitamin E increased pneumonia risk by 68% among those who had the highest exposure to smoking and did not exercise (22% of the ATBC participants). These findings refute there being a uniform effect of vitamin E supplementation on the risk of pneumonia.