| 1. |
- Bui, Christine L, et al.
(author)
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Validation of acute liver injury cases in a population-based cohort study of oral antimicrobial users
- 2014
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In: Current Drug Safety. - : Bentham Science Publishers Ltd.. - 1574-8863 .- 2212-3911. ; 9:1, s. 23-28
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Journal article (peer-reviewed)abstract
- We conducted a cohort study of acute, noninfectious liver injury among oral antimicrobial users. Potential cases were identified in the HealthCore Integrated Research Database (HIRD(SM)) population between July 1, 2001, and March 31, 2009, using ICD-9-CM codes primarily for acute and subacute necrosis of the liver, hepatic coma, and unspecified hepatitis.Liver test results were used to confirm case status according to published criteria. Two physician reviewers experienced in studying acute liver injury (blinded to study drug exposures) evaluated data abstracted from hospital and emergency department records to validate potential cases. Of 715 potential cases having claims associated with any of the primary screening codes, 312 (44%) were valid cases, 108 (15%) were not cases, and 295 (41%) were of uncertain status (records inadequate for validation). Among potential cases with adequate medical records, the PPV for presence of any of the primary codes was 74% (95% CI, 70%-78%). The highest PPV for a single code was for acute and subacute necrosis of the liver (84%; 95% CI, 77%-90%).Evaluation of cases of noninfectious liver injury using hospital and emergency department medical records continues to represent the preferred approach in studies using insurance claims data.
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| 2. |
- Kaye, James A, et al.
(author)
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Risk of acute liver injury associated with the use of moxifloxacin and other oral antimicrobials : a retrospective, population-based cohort study
- 2014
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In: Pharmacotherapy. - : Wiley. - 0277-0008 .- 1875-9114. ; 34:4, s. 336-349
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Journal article (peer-reviewed)abstract
- STUDY OBJECTIVE: To estimate the incidence and relative risk of a hospitalization or emergency visit for noninfectious liver injury in users of eight oral antimicrobials-amoxicillin, amoxicillin-clavulanic acid, clarithromycin, cefuroxime, doxycycline, levofloxacin, moxifloxacin, telithromycin-compared with nonusers of these antimicrobials.DESIGN: Retrospective, observational cohort study with a nested case-control analysis.DATA SOURCE: HealthCore Integrated Research Database.PATIENTS: Adults with continuous health plan enrollment for at least 6 months before study entry who had a new dispensing of a study antimicrobial between July 1, 2001, and March 31, 2009. Cases had diagnoses indicating noninfectious liver injury during follow-up. To control for potentially confounding risk factors, 10 controls at risk for liver injury during follow-up were matched to each case by age, sex, and event date (liver injury date of the case), and analyses were adjusted for medical history, concomitant drugs, and health care service use.MEASUREMENTS AND MAIN RESULTS: Two physician reviewers (blind to exposure) validated the cases. Among 1.3 million antimicrobial users, we identified 607 cases of liver injury, including 82 cases of severe hepatocellular injury and 11 cases of liver failure. Liver injury incidence in nonusers of study antimicrobials was 35/100,000 person-years (95% confidence interval [CI] 29-42/100,000 person-years). For valid cases, the adjusted relative risk among current users of multiple antimicrobials was 3.2 (95% CI 1.6-6.7). Levofloxacin had the highest relative risk for current single use (3.2, 95% CI 1.8-5.8). Relative risks were also elevated for amoxicillin-clavulanic acid (2.5, 95% CI 1.3-5.0), doxycycline (2.5, 95% CI 1.2-5.2), moxifloxacin (2.3, 95% CI 1.1-4.7), and amoxicillin (2.3, 95% CI 1.1-4.7).CONCLUSION: The results support a comparatively high adjusted relative risk of liver injury among patients exposed concurrently to multiple antimicrobials and modest elevations in the risk for several antimicrobials used alone; however, we found little evidence of any strong effect of commonly used antimicrobials on the risk of liver injury.
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| 4. |
- Ekblad, Alf, 1957-, et al.
(author)
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The production and turnover of extramatrical mycelium of ectomycorrhizal fungi in forest soils : role in carbon cycling
- 2013
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In: Plant and Soil. - : Springer Science and Business Media LLC. - 0032-079X .- 1573-5036. ; 366:1-2, s. 1-27
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Research review (peer-reviewed)abstract
- There is growing evidence of the importance of extramatrical mycelium (EMM) of mycorrhizal fungi in carbon (C) cycling in ecosystems. However, our understanding has until recently been mainly based on laboratory experiments, and knowledge of such basic parameters as variations in mycelial production, standing biomass and turnover as well as the regulatory mechanisms behind such variations in forest soils is limited. Presently, the production of EMM by ectomycorrhizal (EM) fungi has been estimated at similar to 140 different forest sites to be up to several hundreds of kg per ha per year, but the published data are biased towards Picea abies in Scandinavia. Little is known about the standing biomass and turnover of EMM in other systems, and its influence on the C stored or lost from soils. Here, focussing on ectomycorrhizas, we discuss the factors that regulate the production and turnover of EMM and its role in soil C dynamics, identifying important gaps in this knowledge. C availability seems to be the key factor determining EMM production and possibly its standing biomass in forests but direct effects of mineral nutrient availability on the EMM can be important. There is great uncertainty about the rate of turnover of EMM. There is increasing evidence that residues of EM fungi play a major role in the formation of stable N and C in SOM, which highlights the need to include mycorrhizal effects in models of global soil C stores.
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| 5. |
- Frisch, M, et al.
(author)
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Cultural bias in the AAP's 2012 Technical Report and Policy Statement on male circumcision
- 2013
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In: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 131:4, s. 796-800
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Journal article (peer-reviewed)abstract
- The American Academy of Pediatrics recently released its new Technical Report and Policy Statement on male circumcision, concluding that current evidence indicates that the health benefits of newborn male circumcision outweigh the risks. The technical report is based on the scrutiny of a large number of complex scientific articles. Therefore, while striving for objectivity, the conclusions drawn by the 8 task force members reflect what these individual physicians perceived as trustworthy evidence. Seen from the outside, cultural bias reflecting the normality of nontherapeutic male circumcision in the United States seems obvious, and the report’s conclusions are different from those reached by physicians in other parts of the Western world, including Europe, Canada, and Australia. In this commentary, a different view is presented by non–US-based physicians and representatives of general medical associations and societies for pediatrics, pediatric surgery, and pediatric urology in Northern Europe. To these authors, only 1 of the arguments put forward by the American Academy of Pediatrics has some theoretical relevance in relation to infant male circumcision; namely, the possible protection against urinary tract infections in infant boys, which can easily be treated with antibiotics without tissue loss. The other claimed health benefits, including protection against HIV/AIDS, genital herpes, genital warts, and penile cancer, are questionable, weak, and likely to have little public health relevance in a Western context, and they do not represent compelling reasons for surgery before boys are old enough to decide for themselves.
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| 6. |
- He, Jia, et al.
(author)
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A population-based survey of the epidemiology of symptom-defined gastroesophageal reflux disease : the Systematic Investigation of Gastrointestinal Diseases in China
- 2010
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In: BMC Gastroenterology. - 1471-230X. ; 10, s. 94-
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Journal article (peer-reviewed)abstract
- Background: The epidemiology of gastroesophageal reflux disease (GERD) has yet to be investigated using the symptomatic threshold criteria recommended by the Montreal Definition. This study aimed to determine the prevalence of symptom-defined GERD across five regions of China, and to investigate variables associated with GERD. Methods: A representative sample of 18 000 adults (aged 18-80 years) were selected equally from rural and urban areas in each region (n = 1800). According to the Montreal Definition, GERD is present when mild symptoms of heartburn and/ or regurgitation occur on >= 2 days a week, or moderate-to-severe symptoms of heartburn and/or regurgitation occur on >= 1 day a week. Results: In total, 16 091 participants completed the survey (response rate: 89.4%) and 16 078 responses were suitable for analysis. Applying the Montreal criteria, the prevalence of symptom-defined GERD was 3.1% and varied significantly (p < 0.001) among the five regions (from 1.7% in Guangzhou to 5.1% in Wuhan) and between rural and urban populations (3.8% vs 2.4%). Factors significantly associated with GERD included living in a rural area and a family history of gastrointestinal diseases. Conclusions: This population-based survey found that the prevalence of symptom-defined GERD in China was 3.1%, which is lower than that found in Western countries.
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| 7. |
- Jick, S. S., et al.
(author)
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Mortality of patients with multiple sclerosis : a cohort study in UK primary care
- 2014
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In: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 261:8, s. 1508-1517
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Journal article (peer-reviewed)abstract
- We aimed to estimate rates, causes and risk factors of all-cause mortality in a large population-based cohort of multiple sclerosis (MS) patients compared with patients without MS. Using data from the UK General Practice Research Database, we identified MS cases diagnosed during 2001-2006 and validated using patients' original records where possible. We also included MS cases during 1993-2000 identified and validated in an earlier study. Cases were matched to up to ten referents without MS by age, sex, index date (date of first MS diagnosis for cases and equivalent reference date for controls), general practice and length of medical history before first MS diagnosis. Patients were followed up to identify deaths; hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox-proportional regression. MS patients (N = 1,822) had a significantly increased risk of all-cause mortality compared with referents (N = 18,211); adjusted HR 1.7 (95 % CI 1.4-2.1). Compared with referents, female MS patients had a higher but not significantly different HR for death than males; adjusted HR 1.86 (95 % CI 1.46-2.38) vs. HR 1.31 (95 % CI 0.93-1.84), respectively. The most commonly recorded cause of death in MS patients was 'MS' (41 %), with a higher proportion recorded among younger patients. A significantly higher proportion of referents than MS patients had cancer recorded as cause of death (40 vs. 19 %). Patients with MS have a significant 1.7-fold increased risk of all-cause mortality compared with the general population. MS is the most commonly recorded cause of death among MS patients.
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| 8. |
- Johansson, Saga, et al.
(author)
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Prospective Drug Safety Monitoring Using the UK Primary-Care General Practice Research Database Theoretical Framework, Feasibility Analysis and Extrapolation to Future Scenarios
- 2010
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In: Drug Safety. - : Springer Science and Business Media LLC. - 0114-5916 .- 1179-1942. ; 33:3, s. 223-232
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Journal article (peer-reviewed)abstract
- Background: Post-launch drug safety monitoring is essential for the detection of adverse drug signals that may be missed during preclinical trials. Traditional methods of postmarketing surveillance such as spontaneous reporting have intrinsic limitations, many of which can be overcome by the additional application of structured pharmacoepidemiological approaches. However, further improvement in drug safety monitoring requires a shift towards more proactive pharmacoepidemiological methods that can detect adverse drug signals as they occur in the population. Objective: To assess the feasibility of using proactive monitoring of an electronic medical record system, in combination with an independent endpoint adjudication committee, to detect adverse events among users of selected drugs. Methods: UK General Practice Research Database (GPRD) information was used to detect acute liver disorder associated with the use of amoxicillin/clavulanic acid (hepatotoxic) or low-dose aspirin (acetylsalicylic acid [non-hepatotoxic]). Individuals newly prescribed these drugs between 1 October 2005 and 31 March 2006 were identified. Acute liver disorder cases were assessed using GPRD computer records in combination with case validation by an independent endpoint adjudication committee. Signal generation thresholds were based on the background rate of acute liver disorder in the general population. Results: Over a 6-month period, 8148 patients newly prescribed amoxicillin/clavulanic acid and 5577 patients newly prescribed low-dose aspirin were identified. Within this cohort, searches identified 11 potential liver disorder cases from computerized records: six for amoxicillin/clavulanic acid and five for low-dose aspirin. The independent endpoint adjudication committee refined this to four potential acute liver disorder cases for whom paper-based information was requested for final case assessment. Final case assessments confirmed no cases of acute liver disorder. The time taken for this study was 18 months (6 months for recruitment and 12 months for data management and case validation). To reach the estimated target exposure necessary to raise or rule out a signal of concern to public health, we determined that a recruitment period 2-3 times longer than that used in this study would be required. Based on the real market uptake of six commonly used medicinal products launched between 2001 and 2006 in the UK (budesonide/eformoterol [fixed-dose combination], duloxetine, ezetimibe, metformin/rosiglitazone [fixed-dose combination], tiotropium bromide and tadalafil) the target exposure would not have been reached until the fifth year of marketing using a single database. Conclusions: It is feasible to set Lip a system that actively monitors drug safety using a healthcare database and an independent endpoint adjudication committee. However, future successful implementation will require multiple databases to be queried so that larger study populations are included. This requires further development and harmonization of international healthcare databases.
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| 9. |
- Sundqvist, Maja K., et al.
(author)
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Interactive effects of vegetation type and elevation on aboveground and belowground properties in a subarctic tundra
- 2011
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In: Oikos. - Copenhagen : Munksgaard. - 0030-1299 .- 1600-0706. ; 120:1, s. 128-142
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Journal article (peer-reviewed)abstract
- An improved knowledge of how contrasting types of plant communities and their associated soil biota differ in their responses to climatic variables is important for better understanding the future impacts of climate change on terrestrial ecosystems. Elevational gradients serve as powerful study systems for answering questions on how ecological processes can be affected by changes in temperature and associated climatic variables. In this study, we evaluated how plant and soil microbial communities, and abiotic soil properties, change with increasing elevation in subarctic tundra in northern Sweden, for each of two dominant but highly contrasting vegetation types, namely heath (dominated by woody dwarf shrubs) and meadow (dominated by herbaceous species). To achieve this, we measured plant community characteristics, microbial community properties and several soil abiotic properties for both vegetation types across an elevation gradient of 500 to 1000 m. We found that the two vegetation types differed not only in several above- and belowground properties, but also in how these properties responded to elevation, pointing to important interactive effects between vegetation type and elevation. Specifically, for the heath, available soil nitrogen and phosphorus decreased with elevation whereas fungal dominance increased, while for the meadow, idiosyncratic responses to elevation for these variables were found. These differences in belowground responses to elevation among vegetation types were linked to shifts in the species and functional group composition of the vegetation. Our results highlight that these two dominant vegetation types in subarctic tundra differ greatly not only in fundamental aboveground and belowground properties, but also in how these properties respond to elevation and are therefore likely to be influenced by temperature. As such they highlight that vegetation type, and the soil abiotic properties that determine this, may serve as powerful determinants of how both aboveground and belowground properties respond to strong environmental gradients.
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