Background Random error may cause misleading evidence in meta-analyses. The required number of participants in a meta-analysis (i.e. information size) should be at least as large as an adequately powered single trial. Trial sequential analysis (TSA) may reduce risk of random errors due to repetitive testing of accumulating data by evaluating meta-analyses not reaching the information size with monitoring boundaries. This is analogous to sequential monitoring boundaries in a single trial. Methods We selected apparently conclusive (P ≤ 0.05) Cochrane neonatal meta-analyses. We applied heterogeneity-adjusted and unadjusted TSA on these meta-analyses by calculating the information size, the monitoring boundaries, and the cumulative Z-statistic after each trial. We identified the proportion of meta-analyses that did not reach the required information size and the proportion of these meta-analyses in which the Z-curve did not cross the monitoring boundaries. Results Of 54 apparently conclusive meta-analyses, 39 (72%) did not reach the heterogeneity-adjusted information size required to accept or reject an intervention effect of 25% relative risk reduction. Of these 39, 19 meta-analyses (49%) were considered inconclusive, because the cumulative Z-curve did not cross the monitoring boundaries. The median number of participants required to reach the required information size was 1591 (range, 339-6149). TSA without heterogeneity adjustment largely confirmed these results. Conclusions Many apparently conclusive Cochrane neonatal meta-analyses may become inconclusive when the statistical analyses take into account the risk of random error due to repetitive testing.
Summary Background In the Global Burden of Disease Study 2013 (GBD 2013), knowledge about health and its determinants has been integrated into a comparable framework to inform health policy. Outputs of this analysis are relevant to current policy questions in England and elsewhere, particularly on health inequalities. We use GBD 2013 data on mortality and causes of death, and disease and injury incidence and prevalence to analyse the burden of disease and injury in England as a whole, in English regions, and within each English region by deprivation quintile. We also assess disease and injury burden in England attributable to potentially preventable risk factors. England and the English regions are compared with the remaining constituent countries of the UK and with comparable countries in the European Union (EU) and beyond. Methods We extracted data from the GBD 2013 to compare mortality, causes of death, years of life lost (YLLs), years lived with a disability (YLDs), and disability-adjusted life-years (DALYs) in England, the UK, and 18 other countries (the first 15 EU members [apart from the UK] and Australia, Canada, Norway, and the USA [EU15+]). We extended elements of the analysis to English regions, and subregional areas defined by deprivation quintile (deprivation areas). We used data split by the nine English regions (corresponding to the European boundaries of the Nomenclature for Territorial Statistics level 1 [NUTS 1] regions), and by quintile groups within each English region according to deprivation, thereby making 45 regional deprivation areas. Deprivation quintiles were defined by area of residence ranked at national level by Index of Multiple Deprivation score, 2010. Burden due to various risk factors is described for England using new GBD methodology to estimate independent and overlapping attributable risk for five tiers of behavioural, metabolic, and environmental risk factors. We present results for 306 causes and 2337 sequelae, and 79 risks or risk clusters. Findings Between 1990 and 2013, life expectancy from birth in England increased by 5·4 years (95% uncertainty interval 5·0–5·8) from 75·9 years (75·9–76·0) to 81·3 years (80·9–81·7); gains were greater for men than for women. Rates of age-standardised YLLs reduced by 41·1% (38·3–43·6), whereas DALYs were reduced by 23·8% (20·9–27·1), and YLDs by 1·4% (0·1–2·8). For these measures, England ranked better than the UK and the EU15+ means. Between 1990 and 2013, the range in life expectancy among 45 regional deprivation areas remained 8·2 years for men and decreased from 7·2 years in 1990 to 6·9 years in 2013 for women. In 2013, the leading cause of YLLs was ischaemic heart disease, and the leading cause of DALYs was low back and neck pain. Known risk factors accounted for 39·6% (37·7–41·7) of DALYs; leading behavioural risk factors were suboptimal diet (10·8% [9·1–12·7]) and tobacco (10·7% [9·4–12·0]). Interpretation Health in England is improving although substantial opportunities exist for further reductions in the burden of preventable disease. The gap in mortality rates between men and women has reduced, but marked health inequalities between the least deprived and most deprived areas remain. Declines in mortality have not been matched by similar declines in morbidity, resulting in people living longer with diseases. Health policies must therefore address the causes of ill health as well as those of premature mortality. Systematic action locally and nationally is needed to reduce risk exposures, support healthy behaviours, alleviate the severity of chronic disabling disorders, and mitigate the effects of socioeconomic deprivation. Funding Bill & Melinda Gates Foundation and Public Health England.
In the third Joint Danube Survey (JDS3), emerging organic contaminants were analysed in the dissolved water phase of samples from the Danube River and its major tributaries. Analyses were performed using solid-phase extraction (SPE) followed by ultra-high-pressure liquid chromatography triple-quadrupole mass spectrometry (UHPLC-MS-MS) and gas chromatography–mass spectrometry (GC–MS). The polar organic compounds analysed by UHPLC-MS-MS were 1H-benzotriazole, methylbenzotriazoles, carbamazepine, 10,11-dihydro-10,11-dihydroxy-carbamazepine, diclofenac, sulfamethox-azole, 2,4-D (2,4-dichlorophenoxyacetic acid), MCPA (2-methyl-4-chlorophenoxyacetic acid), metolachlor, cybutryne (irgarol), terbutryn, DEET ( , -diethyl- -toluamide), and several perfluoroalkyl acids (C –C ; C = perfluorooctanoic acid (PFOA)) and perfluorooctansulfonic acid (PFOS). In addition, several organophosphorus flame retardants were analysed by GC-MS. The most relevant compounds identified in the 71 water samples, in terms of highest median and maximum concentrations, were 1H-benzotriazole, tris(1-chloro-2-propyl)phosphate (TCPP), methylbenzotriazoles, carbama-zepine and its metabolite, DEET, sulfamethoxazole, tris(isobutyl)phosphate (TiBP), tris(2-chloroethyl)phosphate (TCEP), PFOA, PFOS and diclofenac. The concentrations of these compounds in the samples were generally below the environmental quality standard (EQS) threshold values, with the exception of PFOS, the concentration of which exceeded the annual average water EQS limit of 0.65 ng/L along the whole river, and also exceeded the fish biota EQS of 9.1 μg/kg. In addition, the proposed EQS for diclofenac, of 0.1 μg/L, was exceeded in the Arges River in Romania (255 ng/L).
The present study involved segmental testing of hair in two clinical cases with known dosage histories. Hair analysis confirmed the first patient's exposure to the prescribed sertraline and citalopram for several months. Citalopram was generally distributed along the hair shaft in accordance with the drug ingestion period. By contrast, “false” positive results were observed for sertraline in distal hair segments, corresponding to a period of no sertraline exposure, which may indicate incorporation from sweat or sebum, which transport the drugs along the hair surface. The second patient received various drugs during her treatment for brain cancer. Metoclopramide, morphine, oxazepam, paracetamol, sumatriptan, tramadol, and zopiclone, which had been part of the therapy, were all detected in the proximal hair segment. The results of these two cases indicated that results—especially concerning the time of drug intake—must be interpreted with caution and allow for the possibility of incorporation from sweat or sebum.
While working on the concept of employing human faces as a biometric tool for personal identification, it is common to come across certain hindrances such as illumination, pose variation and facial hair. But, dealing with the aging process of an individual has been generally overlooked until recently. This relatively untouched aspect may enable us more insight while tackling identification problems. As the face matures, it changes some of its most enduring properties (e.g., shape of the cranium) and acquires new attributes (e.g., wrinkles). These changes are the basis of information about the aging of the face. The human brain can analyze the face and estimate the approximate age of an individual, though this estimation is not accurate. The perception of age in the human brain is still a subject of research. This article takes the phenomenon of “aging of face” into consideration and following the same, this study has been carried out to analyze the kind of change occurring in the facial soft tissue thickness with progression of age and can be used along with other biological markers for personal identification or in developing automatic facial age estimation. The data can be used as an additional feature for corroboration or authentication in individualization. This preliminary study will help in forensic investigation although a database needs to be generated on other populations.
Meta-analysis is a method to obtain a weighted average of results from various studies. In addition to pooling effect sizes, meta-analysis can also be used to estimate disease frequencies, such as incidence and prevalence. In this article we present methods for the meta-analysis of prevalence. We discuss the logit and double arcsine transformations to stabilise the variance. We note the special situation of multiple category prevalence, and propose solutions to the problems that arise. We describe the implementation of these methods in the MetaXL software, and present a simulation study and the example of multiple sclerosis from the Global Burden of Disease 2010 project. We conclude that the double arcsine transformation is preferred over the logit, and that the MetaXL implementation of multiple category prevalence is an improvement in the methodology of the meta-analysis of prevalence.
In healthcare settings drug diversion and impairment of physicians are major concerns requiring a rapid and efficient method for surveillance and detection. A Direct Analysis in Real Time ion source coupled to a JEOL AccuTOFTM time-of-flight mass spectrometer (DART-MS) method was developed to screen parenteral pharmaceutical formulations for potential drug diversion. Parenteral pharmaceutical formulations are also known as injectable formulations and are used with intravenous, subcutaneous, intramuscular and intra-articular administration. A library was created using the mass spectra data collected by a DART-MS operated in switching mode at 20, 60 and 90 V settings. This library contained 17 commonly encountered drugs in parenteral pharmaceutical formulations that included the surgical analgesic: fentanyl, hydromorphone and morphine; anesthetic: baclofen, bupivacaine, ketamine, midazolam, ropivacaine and succinylcholine; and a mixture of other drug classes: caffeine, clonidine, dexamethasone, ephedrine, heparin, methadone, oxytocin and phenylephrine. Randomly selected 200 de-identified parenteral pharmaceutical formulations containing one or more drugs were submitted for analysis to the FIRM Toxicology Laboratory at Virginia Commonwealth University Health and were screened using the DART-MS. The drug contents of the de-identified formulations were previously confirmed by a published high performance liquid chromatography (HPLC) method. The drugs in the formulations were rapidly and successfully identified using the generated library. The DART-MS and HPLC results were in complete agreement for all 200 parenteral pharmaceutical formulations.
Summary Background Malaria is one of the greatest causes of mortality worldwide. Use of the most effective treatments for malaria remains inadequate for those in need, and there is concern over the emergence of resistance to these treatments. In 2010, the Global Fund launched the Affordable Medicines Facility—malaria (AMFm), a series of national-scale pilot programmes designed to increase the access and use of quality-assured artemisinin based combination therapies (QAACTs) and reduce that of artemisinin monotherapies for treatment of malaria. AMFm involves manufacturer price negotiations, subsidies on the manufacturer price of each treatment purchased, and supporting interventions such as communications campaigns. We present findings on the effect of AMFm on QAACT price, availability, and market share, 6–15 months after the delivery of subsidised ACTs in Ghana, Kenya, Madagascar, Niger, Nigeria, Uganda, and Tanzania (including Zanzibar). Methods We did nationally representative baseline and endpoint surveys of public and private sector outlets that stock antimalarial treatments. QAACTs were identified on the basis of the Global Fund's quality assurance policy. Changes in availability, price, and market share were assessed against specified success benchmarks for 1 year of AMFm implementation. Key informant interviews and document reviews recorded contextual factors and the implementation process. Findings In all pilots except Niger and Madagascar, there were large increases in QAACT availability (25·8–51·9 percentage points), and market share (15·9–40·3 percentage points), driven mainly by changes in the private for-profit sector. Large falls in median price for QAACTs per adult equivalent dose were seen in the private for-profit sector in six pilots, ranging from US$1·28 to $4·82. The market share of oral artemisinin monotherapies decreased in Nigeria and Zanzibar, the two pilots where it was more than 5% at baseline. Interpretation Subsidies combined with supporting interventions can be effective in rapidly improving availability, price, and market share of QAACTs, particularly in the private for-profit sector. Decisions about the future of AMFm should also consider the effect on use in vulnerable populations, access to malaria diagnostics, and cost-effectiveness. Funding The Global Fund to Fight AIDS, Tuberculosis and Malaria, and the Bill & Melinda Gates Foundation.
The occurrence of seven trace elements and forty three antibiotics was investigated in manure-based fertilizers from the Zhejiang province of China. These trace elements included copper, zinc, arsenic, chromium, mercury, lead and cadmium. The targeted antibiotics included four groups: sulfonamides, tetracyclines, fluoroquinolones and chloramphenicols. The median amounts of copper, zinc, arsenic, chromium, mercury, lead and cadmium in the analyzed samples were 160, 465, 7.9, 21.2, 0.3, 8.1 and 0.6 mg·kg , respectively. Seventeen antibiotics were detected. Enrofloxacin was the most frequently detected compound, with a detection rate of 39.3% and concentrations ranging from 6.7 μg·kg to 4091 μg·kg . Based on the referred loading rates in agricultural soil, 10% of the collected manure-based fertilizer samples might pose a high potential ecological risk due to the presence of antibiotics. Occurrence of seven trace elements and forty three antibiotics was investigated in manure-based fertilizers in Zhejiang province of China. The trace elements included copper, zinc, arsenic, chromium, mercury, lead and cadmium; the targeted antibiotics included four groups: sulfonamides, tetracyclines, fluoroquinolones and chloramphenicols. The medium values of copper, zinc, arsenic, chromium, mercury, lead and cadmium in the analyzed samples were 160, 465, 7.9, 21.2, 0.3, 8.1 and 0.6 mg·kg , respectively. Seventeen antibiotics were detected. Enrofloxacin was the most frequently detected compound with the detection rate of 39.3% and the concentrations ranged from 6.7 μg·kg to 4091 μg·kg . Based on the referred loading rates, 10% of the collected manure-based fertilizers might pose a high potential ecological risk after their application onto agriculture soil due to the presence of antibiotics.
This paper examines the objectives for performing sensitivity analysis in medical cost-effectiveness analysis and the implications of expected utility maximization for methods to perform such analyses. The analysis suggests specific approaches for optimal decision making under uncertainty and specifying such decisions for subgroups based on the ratio of expected costs to expected benefits, and for valuing research using value of information calculations. Though ideal value of information calculations may be difficult, certain approaches with less stringent data requirements may bound the value of information. These approaches suggest methods by which the vast cost-effectiveness literature may help inform priorities for medical research. (C) 2001 Elsevier Science B.V.