Summary Background Alzheimer's disease biomarkers are important for early diagnosis in routine clinical practice and research. Three core CSF biomarkers for the diagnosis of Alzheimer's disease ...(Aβ42, T-tau, and P-tau) have been assessed in numerous studies, and several other Alzheimer's disease markers are emerging in the literature. However, there have been no comprehensive meta-analyses of their diagnostic performance. We systematically reviewed the literature for 15 biomarkers in both CSF and blood to assess which of these were most altered in Alzheimer's disease. Methods In this systematic review and meta-analysis, we screened PubMed and Web of Science for articles published between July 1, 1984, and June 30, 2014, about CSF and blood biomarkers reflecting neurodegeneration (T-tau, NFL, NSE, VLP-1, and HFABP), APP metabolism (Aβ42, Aβ40, Aβ38, sAPPα, and sAPPβ), tangle pathology (P-tau), blood–brain-barrier function (albumin ratio), and glial activation (YKL-40, MCP-1, and GFAP). Data were taken from cross-sectional cohort studies as well as from baseline measurements in longitudinal studies with clinical follow-up. Articles were excluded if they did not contain a cohort with Alzheimer's disease and a control cohort, or a cohort with mild cognitive impairment due to Alzheimer's disease and a stable mild cognitive impairment cohort. Data were extracted by ten authors and checked by two for accuracy. For quality assessment, modified QUADAS criteria were used. Biomarker performance was rated by random-effects meta-analysis based on the ratio between biomarker concentration in patients with Alzheimer's disease and controls (fold change) or the ratio between biomarker concentration in those with mild cognitive impariment due to Alzheimer's disease and those with stable mild cognitive impairment who had a follow-up time of at least 2 years and no further cognitive decline. Findings Of 4521 records identified from PubMed and 624 from Web of Science, 231 articles comprising 15 699 patients with Alzheimer's disease and 13 018 controls were included in this analysis. The core biomarkers differentiated Alzheimer's disease from controls with good performance: CSF T-tau (average ratio 2·54, 95% CI 2·44–2·64, p<0·0001), P-tau (1·88, 1·79–1·97, p<0·0001), and Aβ42 (0·56, 0·55–0·58, p<0·0001). Differentiation between cohorts with mild cognitive impairment due to Alzheimer's disease and those with stable mild cognitive impairment was also strong (average ratio 0·67 for CSF Aβ42, 1·72 for P-tau, and 1·76 for T-tau). Furthermore, CSF NFL (2·35, 1·90–2·91, p<0·0001) and plasma T-tau (1·95, 1·12–3·38, p=0·02) had large effect sizes when differentiating between controls and patients with Alzheimer's disease, whereas those of CSF NSE, VLP-1, HFABP, and YKL-40 were moderate (average ratios 1·28–1·47). Other assessed biomarkers had only marginal effect sizes or did not differentiate between control and patient samples. Interpretation The core CSF biomarkers of neurodegeneration (T-tau, P-tau, and Aβ42), CSF NFL, and plasma T-tau were strongly associated with Alzheimer's disease and the core biomarkers were strongly associated with mild cognitive impairment due to Alzheimer's disease. Emerging CSF biomarkers NSE, VLP-1, HFABP, and YKL-40 were moderately associated with Alzheimer's disease, whereas plasma Aβ42 and Aβ40 were not. Due to their consistency, T-tau, P-tau, Aβ42, and NFL in CSF should be used in clinical practice and clinical research. Funding Swedish Research Council, Swedish State Support for Clinical Research, Alzheimer's Association, Knut and Alice Wallenberg Foundation, Torsten Söderberg Foundation, Alzheimer Foundation (Sweden), European Research Council, and Biomedical Research Forum.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Numerous observational studies suggest that preventable adverse drug reactions are a significant burden in healthcare, but no meta-analysis using a standardised definition for adverse drug reactions ...exists. The aim of the study was to estimate the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions in adult outpatients and inpatients.
Studies were identified through searching Cochrane, CINAHL, EMBASE, IPA, Medline, PsycINFO and Web of Science in September 2010, and by hand searching the reference lists of identified papers. Original peer-reviewed research articles in English that defined adverse drug reactions according to WHO's or similar definition and assessed preventability were included. Disease or treatment specific studies were excluded. Meta-analysis on the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions was conducted.
Data were analysed from 16 original studies on outpatients with 48797 emergency visits or hospital admissions and from 8 studies involving 24128 inpatients. No studies in primary care were identified. Among adult outpatients, 2.0% (95% confidence interval (CI): 1.2-3.2%) had preventable adverse drug reactions and 52% (95% CI: 42-62%) of adverse drug reactions were preventable. Among inpatients, 1.6% (95% CI: 0.1-51%) had preventable adverse drug reactions and 45% (95% CI: 33-58%) of adverse drug reactions were preventable.
This meta-analysis corroborates that preventable adverse drug reactions are a significant burden to healthcare among adult outpatients. Among both outpatients and inpatients, approximately half of adverse drug reactions are preventable, demonstrating that further evidence on prevention strategies is required. The percentage of patients with preventable adverse drug reactions among inpatients and in primary care is largely unknown and should be investigated in future research.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A systematic review of the nonsurgical treatment of patients with appendiceal abscess or phlegmon, with emphasis on the success rate, need for drainage of abscesses, risk of undetected serious ...disease, and need for interval appendectomy to prevent recurrence.
Patients with appendiceal abscess or phlegmon are traditionally managed by nonsurgical treatment and interval appendectomy. This practice is controversial with proponents of immediate surgery and others questioning the need for interval appendectomy.
A Medline search identified 61 studies published between January 1964 and December 2005 reporting on the results of nonsurgical treatment of appendiceal abscess or phlegmon. The results were pooled taking the potential clustering on the study-level into account. A meta-analysis of the morbidity after immediate surgery compared with that after nonsurgical treatment was performed.
Appendiceal abscess or phlegmon is found in 3.8% (95% confidence interval (CI), 2.6-4.9) of patients with appendicitis. Nonsurgical treatment fails in 7.2% (CI: 4.0-10.5). The need for drainage of an abscess is 19.7% (CI: 11.0-28.3). Immediate surgery is associated with a higher morbidity compared with nonsurgical treatment (odds ratio, 3.3; CI: 1.9-5.6; P < 0.001). After successful nonsurgical treatment, a malignant disease is detected in 1.2% (CI: 0.6-1.7) and an important benign disease in 0.7% (CI: 0.2-11.9) during follow-up. The risk of recurrence is 7.4% (CI: 3.7-11.1).
The results of this review of mainly retrospective studies support the practice of nonsurgical treatment without interval appendectomy in patients with appendiceal abscess or phlegmon.
Preterm birth is the leading cause of death in children younger than 5 years worldwide. Although preterm survival rates have increased in high-income countries, preterm newborns still die because of ...a lack of adequate newborn care in many low-income and middle-income countries. We estimated global, regional, and national rates of preterm birth in 2014, with trends over time for some selected countries.
We systematically searched for data on preterm birth for 194 WHO Member States from 1990 to 2014 in databases of national civil registration and vital statistics (CRVS). We also searched for population-representative surveys and research studies for countries with no or limited CRVS data. For 38 countries with high-quality data for preterm births in 2014, data are reported directly. For countries with at least three data points between 1990 and 2014, we used a linear mixed regression model to estimate preterm birth rates. We also calculated regional and global estimates of preterm birth for 2014.
We identified 1241 data points across 107 countries. The estimated global preterm birth rate for 2014 was 10·6% (uncertainty interval 9·0–12·0), equating to an estimated 14·84 million (12·65 million–16·73 million) live preterm births in 2014. 12· 0 million (81·1%) of these preterm births occurred in Asia and sub-Saharan Africa. Regional preterm birth rates for 2014 ranged from 13·4% (6·3–30·9) in North Africa to 8·7% (6·3–13·3) in Europe. India, China, Nigeria, Bangladesh, and Indonesia accounted for 57·9 million (41×4%) of 139·9 million livebirths and 6·6 million (44×6%) of preterm births globally in 2014. Of the 38 countries with high-quality data, preterm birth rates have increased since 2000 in 26 countries and decreased in 12 countries. Globally, we estimated that the preterm birth rate was 9×8% (8×3–10×9) in 2000, and 10×6% (9×0–12×0) in 2014.
Preterm birth remains a crucial issue in child mortality and improving quality of maternal and newborn care. To better understand the epidemiology of preterm birth, the quality and volume of data needs to be improved, including standardisation of definitions, measurement, and reporting.
WHO and the March of Dimes.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ
To examine the external validity of the Family Affluence Scale (FAS) among adolescents in Sweden by using register data for parental earned income, level of education and occupational status.
Data ...from the baseline (2015-2019) of the Study of Adolescence Resilience and Stress (STARS), comprising 2283 13-year-olds in the region of Västra Götaland, were used. The FAS III consists of six items: unshared bedroom, car ownership, computer/tablet ownership, dishwasher, number of bathrooms and number of holidays abroad. Register data regarding earned income, educational level and occupational status from Statistics Sweden (2014-2018) were linked to adolescents. In total, survey data were available for 2280 adolescents, and register data were available for 2258 mothers and 2204 fathers.
Total parental earned income was moderately correlated with adolescents' scoring on FAS (0.31 < r < 0.48, p < 0.001), depending on examination year. The low FAS group mainly comprised low-income households, and the high FAS group mainly comprised high-income households. Correlations between mothers' and fathers' educational level and adolescents' scoring on FAS were low (r = 0.19 and r = 0.21, respectively, p < 0.001). FAS was higher among adolescents whose parents were working, but the correlation between parents' occupational status and FAS was low (r = 0.22, p < 0.001).
The FAS can mainly identify low- and high-income households in Sweden. It may be used as an alternative measure of parental earned income in studies using self-reported socioeconomic status among adolescents.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The timing of the first antenatal care visit is paramount for ensuring optimal health outcomes for women and children, and it is recommended that all pregnant women initiate antenatal care in the ...first trimester of pregnancy (early antenatal care visit). Systematic global analysis of early antenatal care visits has not been done previously. This study reports on regional and global estimates of the coverage of early antenatal care visits from 1990 to 2013.
Data were obtained from nationally representative surveys and national health information systems. Estimates of coverage of early antenatal care visits were generated with linear regression analysis and based on 516 logit-transformed observations from 132 countries. The model accounted for differences by data sources in reporting the cutoff for the early antenatal care visit.
The estimated worldwide coverage of early antenatal care visits increased from 40·9% (95% uncertainty interval UI 34·6–46·7) in 1990 to 58·6% (52·1–64·3) in 2013, corresponding to a 43·3% increase. Overall coverage in the developing regions was 48·1% (95% UI 43·4–52·4) in 2013 compared with 84·8% (81·6–87·7) in the developed regions. In 2013, the estimated coverage of early antenatal care visits was 24·0% (95% UI 21·7–26·5) in low-income countries compared with 81·9% (76·5–87·1) in high-income countries.
Progress in the coverage of early antenatal care visits has been achieved but coverage is still far from universal. Substantial inequity exists in coverage both within regions and between income groups. The absence of data in many countries is of concern and efforts should be made to collect and report coverage of early antenatal care visits to enable better monitoring and evaluation.
Department of Reproductive Health and Research, WHO and UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ
To study seasonal inter-individual and intra-individual variations in serum 25-hydroxy vitamin D (25(OH)D) and to explore parameters associated with 25(OH)D in a healthy Swedish adult population. 540 ...blood donors (60 % men; mean age 41 ± 13 years) and 75 thrombocyte donors (92 % men, aged 46 ± 11 years) were included. Serum was collected during 12 months and analyzed for 25(OH)D and parathyroid hormone (S-iPTH). The blood donors answered questionnaires concerning vitamin D supplements, smoking, physical activity, sunbed use and sun holidays. Repeated serum samples were collected from the thrombocyte donors to study the intra-individual variations in S-25(OH)D. S-25(OH)D varied greatly over the year correlating with the intensity of the UV-B irradiation (
r
S
= 0.326;
p
< 0.001). During January–March, a S-25(OH)D level below the thresholds of 50 and 75 nmol/L was observed in 58 and 88 %, respectively, and during July–September in 11 and 50 % (
p
< 0.001). S-25(OH)D was negatively correlated with body mass index and S-iPTH, but was significantly higher in holiday makers in sunny destinations, sunbed users, non-smokers, and in the physically active. The intra-individual analyses showed a mean increase in S-25(OH)D by 8 nmol/L/month between April and August. Approximately 75 % had serum 25(OH)D values <75 nmol/L during 75 % of the year and 50 % had serum 25(OH)D <50 nmol/L during 50 % of the year. Serum 25(OH)D was strongly associated with parameters related to sun exposure, but only weakly with intake of vitamin D supplements.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Early diagnosis and prompt, effective treatment of uncomplicated malaria is critical to prevent severe disease, death and malaria transmission. We assessed the impact of rapid malaria diagnostic ...tests (RDTs) by community health workers (CHWs) on provision of artemisinin-based combination therapy (ACT) and health outcome in fever patients.
Twenty-two CHWs from five villages in Kibaha District, a high-malaria transmission area in Coast Region, Tanzania, were trained to manage uncomplicated malaria using RDT aided diagnosis or clinical diagnosis (CD) only. Each CHW was randomly assigned to use either RDT or CD the first week and thereafter alternating weekly. Primary outcome was provision of ACT and main secondary outcomes were referral rates and health status by days 3 and 7. The CHWs enrolled 2930 fever patients during five months of whom 1988 (67.8%) presented within 24 hours of fever onset. ACT was provided to 775 of 1457 (53.2%) patients during RDT weeks and to 1422 of 1473 (96.5%) patients during CD weeks (Odds Ratio (OR) 0.039, 95% CI 0.029-0.053). The CHWs adhered to the RDT results in 1411 of 1457 (96.8%, 95% CI 95.8-97.6) patients. More patients were referred on inclusion day during RDT weeks (10.0%) compared to CD weeks (1.6%). Referral during days 1-7 and perceived non-recovery on days 3 and 7 were also more common after RDT aided diagnosis. However, no fatal or severe malaria occurred among 682 patients in the RDT group who were not treated with ACT, supporting the safety of withholding ACT to RDT negative patients.
RDTs in the hands of CHWs may safely improve early and well-targeted ACT treatment in malaria patients at community level in Africa.
ClinicalTrials.gov NCT00301015.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background Several highly publicised rapes and murders of young women in India and South Africa have focused international attention on sexual violence. These cases are extremes of the wider ...phenomenon of sexual violence against women, but the true extent is poorly quantified. We did a systematic review to estimate prevalence. Methods We searched for articles published from Jan 1, 1998, to Dec 31, 2011, and manually search reference lists and contacted experts to identify population-based data on the prevalence of women's reported experiences of sexual violence from age 15 years onwards, by anyone except intimate partners. We used random effects meta-regression to calculate adjusted and unadjusted prevalence for regions, which we weighted by population size to calculate the worldwide estimate. Findings We identified 7231 studies from which we obtained 412 estimates covering 56 countries. In 2010 7·2% (95% CI 5·2–9·1) of women worldwide had ever experienced non-partner sexual violence. The highest estimates were in sub-Saharan Africa, central (21%, 95% CI 4·5–37·5) and sub-Saharan Africa, southern (17·4%, 11·4–23·3). The lowest prevalence was for Asia, south (3·3%, 0–8·3). Limited data were available from sub-Saharan Africa, central, North Africa/Middle East, Europe, eastern, and Asia Pacific, high income. Interpretation Sexual violence against women is common worldwide, with endemic levels seen in some areas, although large variations between settings need to be interpreted with caution because of differences in data availability and levels of disclosure. Nevertheless, our findings indicate a pressing health and human rights concern. Funding South African Medical Research Council, Sigrid Rausing Trust, WHO.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The aim was to investigate whether children born after assisted reproduction technology (ART), particularly after frozen-thawed embryo transfer (FET), are at higher risk of childhood cancer than ...children born after fresh embryo transfer and spontaneous conception. We performed a registry-based cohort study using data from the 4 Nordic countries: Denmark, Finland, Norway, and Sweden. The study included 7,944,248 children, out of whom 171,774 children were born after use of ART (2.2%) and 7,772,474 children were born after spontaneous conception, representing all children born between the years 1994 to 2014 in Denmark, 1990 to 2014 in Finland, 1984 to 2015 in Norway, and 1985 to 2015 in Sweden. Rates for any cancer and specific cancer groups in children born after each conception method were determined by cross-linking national ART registry data with national cancer and health data registries and population registries. We used Cox proportional hazards models to estimate the risk of any cancer, with age as the time scale. Children born after FET had a higher risk of childhood cancer than children born after fresh embryo transfer and spontaneous conception. The results should be interpreted cautiously based on the small number of children with cancer, but the findings raise concerns considering the increasing use of FET, in particular freeze-all strategies without clear medical indications.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
