World Health Organization Study Group Research Articles

WHO classification of meningiomas–A single institutional experience

IntroductionMeningiomas are among the most common intracranial neoplasms worldwide. The World Health Organization (WHO) has classified the neoplasm into three grades with each grade having several histological variants. Several studies done in blacks have shown differences with Caucasian populations regarding the occurrence of histological variants. Our study sought to examine the histological variants of meningioma seen in a predominantly black population using the WHO grading system. MethodsWe conducted a retrospective study of all meningiomas seen in our hospital facility for over twenty years. An analysis of data from all the patients diagnosed with meningioma, who also had surgical biopsies taken, was done. The meningiomas were graded using the WHO grading system and also classified into different histological variants within each grade as described by the WHO study group. ResultsThe study included a total number of 163 biopsies. There were more females diagnosed with meningiomas with a female to male ratio of 1.4. Most of the tumors were grade one, however, there were more males with malignant meningiomas. Transitional meningiomas were the most commonly seen variants among the grade one tumors while atypical and anaplastic were most common in grades two and three, respectively. ConclusionA larger population-based study is needed to provide epidemiological data on the occurrence of meningiomas in blacks.

Changes in the quality of life following surgery for hyperhidrosis

Hyperhidrosis is characterized by diaphoresis that is unrelated to the physiological thermo- regulatory requirements of the body. Primary hyperhidrosis is caused by an idiopathic overactivity of the sympathetic nervous system and can affect the axillae, in more than half of the cases, palms, soles and face. As a result, patients may develop psychologic disorders, such as anxiety and depression, or experience impaired quality of life (QOL). Set of indicators were therefore introduced to describe the relationship between QOL post-surgery for hyperhidrosis and daily life. Recently a World Health Organization study group developed a questionnaire made of 100 question ranging from physical, psychological, environmental and spiritual aspects (WHOQOL0-100); this has been followed by a shorter one (WHOQOL BREF) easier to be completed maintaining the same standard of psychometric assessment. This is made of 26 questions covering the same aspects as the WHOQOL-100 representing however a generic tool to assess QOL. Nevertheless there are other QOL indicators that have to be considered when assessing the impact of primary hyperhidrosis (PH) and postoperative status following surgery for PH.

Aldehyde and Volatile Organic Compound Yields in Commercial Cigarette Mainstream Smoke Are Mutually Related and Depend on the Sugar and Humectant Content in Tobacco.

IntroductionThe World Health Organization (WHO) Framework Convention on Tobacco control recognizes the need for tobacco product regulation. In line with that, the WHO Study Group on Tobacco Product Regulation (TobReg) proposed to regulate nine toxicants in mainstream cigarette smoke, including aldehydes, volatile organic compounds (VOCs), and carbon monoxide (CO). We analyzed their relations in 50 commercially available cigarette brands, using two different smoking regimes, and their dependence on sugar and humectant concentrations in tobacco filler.MethodsWe measured sugar and humectant in tobacco filler and aldehydes, VOCs, and tar, nicotine, and CO (TNCO) in mainstream smoke. The general statistics, correlations between emission yields, and correlations between contents and emissions yields were determined for these data.ResultsFor aldehydes, several significant correlations were found with precursor ingredients in unburnt tobacco when smoked with the Intense regime, most prominently for formaldehyde with sucrose, glucose, total sugars, and glycerol. For VOCs, 2,5-dimethylfuran significantly correlates with several sugars under both International Standards Organization (ISO) and Intense smoking conditions. A correlation network visualization shows connectivity between a sugar cluster, an ISO cluster, and an Intense cluster, with Intense formaldehyde as a central highest connected hub.ConclusionsOur multivariate analysis showed several strong connections between the compounds determined. The toxicants proposed by WHO, in particular, formaldehyde, can be used to monitor yields of other toxicants under Intense conditions. Emissions of formaldehyde, acetaldehyde, acrolein, and 2,5-dimethylfuran may decrease when sugar and humectants contents are lowered in tobacco filler.ImplicationsOur findings suggest that the aldehydes and VOCs proposed by TobReg are a representative selection for smoke component market monitoring purposes. In particular, formaldehyde yields may be useful to monitor emissions of other toxicants under Intense conditions. Since the most and strongest correlations were observed with the Intense regime, policymakers are advised to prescribe this regime for regulatory purposes. Policymakers should also consider sugars and humectants contents as targets for future tobacco product regulations, with the additional advantage that consumer acceptance of cigarette smoke is proportional to their concentrations in the tobacco blend.

Risk assessment of toxicants on WHO TobReg priority list in mainstream cigarette smoke using human-smoked yields of Korean smokers

Recently, the World Health Organization Study Group on Tobacco Product Regulation (WHO TobReg) announced a priority list of 38 toxicants among the more than 7000 chemicals found in cigarette smoke, building upon previous lists of toxicants in cigarette smoke. Here, we conducted a comprehensive study on the quantitative exposure and risk characterization of these priority toxicants in mainstream cigarette smoke listed by the WHO TobReg. The human-smoked toxicant yields estimated from spent cigarette butts of a total of 361 smokers using the part-filter method (PFM) were applied to current exposure and risk estimation for the first time. The PFM can estimate human-smoked yields of toxicants using smokers’ maximum mouth-level exposure. The human-smoked yield of each toxicant was converted to systemic uptake by considering bioavailability. Risk indicators—including the incremental lifetime cancer risk (ILCR), cumulative ILCR, hazard quotient (HQ), hazard indices (HIs), and margin of exposure (MOE)—were estimated from the systemic uptake of toxicants combined with Korean exposure factors by gender and age group as well as for total smokers. It was demonstrated that cigarette smoking results in significant cancer and non-cancer health risks. A sensitivity analysis showed that the human-smoked toxicant yield is one of the most important contributors to risk level variations. Our risk estimation suggested that previous risk assessments might have ignored or underestimated the uncertainty of risk assessment. In conclusion, we assessed the risk level of the 38 toxicants on the priority list developed by the WHO TobReg and provided a Korean-specific priority list for the regulations on the emission of cigarette smoke.

Spectrophotometric determination of ammonia levels in tobacco fillers of and sidestream smoke from different cigarette brands in Japan

BackgroundThe ammonia contained in tobacco fillers and mainstream and sidestream cigarette smoke accelerates nicotine dependence in cigarette smokers. Ammonia has been included in the non-exhaustive priority list of 39 tobacco components and emissions of cigarette published by the World Health Organization (WHO) Study Group on Tobacco Product Regulation. The development of a simple ammonia detection method will contribute to the establishment of tobacco product regulation under tobacco control policies and allow surveys to be conducted, even by laboratories with small research budgets.MethodsWe developed a simple colorimetric method based on the salicylate-chlorine reaction and absorption spectrometry with two reagents (sodium nitroprusside and sodium dichloroisocyanurate). To compare this method to conventional ion chromatography, we analyzed the ammonia levels in tobacco fillers extracted from 35 Japanese commercially marketed cigarette brands manufactured by four tobacco companies (Japan Tobacco (JT) Inc., British American Tobacco (BAT), Philip Morris Japan, and Natural American Spirit). We also analyzed the ammonia levels in the sidestream smoke from cigarettes of the brands that were found to contain high or low tobacco filler ammonia levels.ResultsThe ammonia levels in the reference cigarette (3R4F) measured by our method and ion chromatography were similar and comparable to previously reported levels. The ammonia levels in tobacco fillers extracted from 35 cigarette brands ranged from 0.25 to 1.58 mg/g. The mean ammonia level of JT cigarette brands was significantly higher (0.83 ± 0.28 mg/g) than that of Natural American Spirit cigarette brands (0.30 ± 0.08 mg/g) and lower than those in the other two cigarette brands (1.11 ± 0.19 mg/g for BAT and 1.24 ± 0.15 mg/g for Philip Morris) (p < 0.001 by Bonferroni test). The ammonia levels in the sidestream smoke of CABIN, Marlboro Black Menthol, American Spirit Light, and Seven Stars were 5.89 ± 0.28, 5.23 ± 0.12, 6.92 ± 0.56, and 4.14 ± 0.19 mg/cigarette, respectively. The ammonia levels were higher in sidestream smoke than in tobacco filler.ConclusionsOur simple colorimetric could be used to analyze ammonia in tobacco fillers and sidestream smoke. There were significant differences between the ammonia levels of the 35 commercially marketed cigarette brands in Japan manufactured by four tobacco manufacturers. Over 90% of the ammonia in sidestream smoke was in gaseous phase.

Assessment of novel tobacco heating product THP1.0. Part 3: Comprehensive chemical characterisation of harmful and potentially harmful aerosol emissions

For a tobacco heating product (THP), which heats rather than burns tobacco, the emissions of toxicants in the aerosol were compared with those in cigarette smoke under a machine-puffing regimen of puff volume 55 ml, puff duration 2 s and puff interval 30 s. The list of toxicants included those proposed by Health Canada, the World Health Organization Study Group on Tobacco Product Regulation (TobReg), the US Food and Drug Administration and possible thermal breakdown products. In comparison to the University of Kentucky 3R4F reference cigarette the toxicant levels in the THP1.0 emissions were significantly reduced across all chemical classes. For the nine toxicants proposed by TobReg for mandated reduction in cigarette emissions, the mean reductions in THP1.0 aerosol were 90.6–99.9% per consumable with an overall average reduction of 97.1%. For the abbreviated list of harmful and potentially harmful constituents of smoke specified by the US Food and Drug Administration Tobacco Products Scientific Advisory Committee for reporting in cigarette smoke (excluding nicotine), reductions in the aerosol of THP1.0 were 84.6–99.9% per consumable with an overall average reduction of 97.5%.

Influence of measurement uncertainty on the world health organization recommended regulation for mainstream cigarette smoke constituents

The World Health Organization Study Group on Tobacco Product Regulation (WHO TobReg) proposed mandated ceilings on 9 prioritized mainstream cigarette smoke constituents determined from the market-specific median of nicotine-normalized yield distributions. Considering the requirements for assessing and reporting of compliance with ceilings, it is of great importance to estimate the measurement uncertainty. To have a better understanding of influence of measurement uncertainty on the WHO recommended regulation for cigarette smoke constituents, in the present study, the measurement uncertainties were evaluated systematically based on series of collaborative studies reported by three different authorities over the years from 2012 to 2016, according to the approaches guided in ISO/TS 21748. Furthermore, the compliance assessment of 20 representative cigarette samples with proposed ceilings was conducted by taking measurement uncertainty into account. This work demonstrated that measurement uncertainty had great influence on the implementation of the regulated mandated lowering of toxic smoke constituents, both on the setting of ceilings and the compliance assessment as well.

Health-related Quality of Life in Accordance with Fracture History and Comorbidities in Korean Patients with Osteoporosis.

BackgroundThe purpose of this study was to explore health-related quality of life (HRQOL) among Korean patients with osteoporosis and to measure the impact of fractures and comorbidity on their quality of life (QOL) using the Korean National Health and Nutrition Examination Survey (KNHANES) data with a nationwide representativeness.MethodsThis study was based on 4-year-data obtained from the KNHANES 2008 to 2011. Osteoporosis was diagnosed in 2,078 survey participants according to their bone mineral density measurements using dual energy X-ray absorptiometry. According to the World Health Organization study group, T-scores at or above -1.0 are considered normal, those between -1.0 and -2.5 as osteopenia, and those at or below -2.5 as osteoporosis The EuroQol five-dimensional questionnaire (EQ-5D) index score was used to assess the QOL.ResultsOf 2,078 patients diagnosed with osteoporosis, fractures were found to occur at 11.02%. Wrist fracture was the most frequent, affecting 4.52% of the patients, with a significantly different prevalence among men and women (P<0.001). The overall EQ-5D index score was 0.84±0.01 among patients with osteoporosis. With the exception of cancer, the EQ-5D index score were significantly lower for those having osteoarthritis, rheumatoid arthritis, hypertension, diabetes, chronic obstructive pulmonary disease and cardiovascular events compared to those without the related diseases.ConclusionsWe found that low health utility was associated with previous spine fracture and comorbidities in patients with osteoporosis. In particular, the number of fracture experiences greatly deteriorated the HRQOL in patients with osteoporosis. Thus, prevention of secondary fractures and chronic care model for comorbidities should be a priority for osteoporosis management in order to improve HRQOL.

Fibrocalculus Pancreatic Diabetes in a Young Female: A Rare Form of Secondary Diabetes

Fibrocalculus pancreatic diabetes (FCPD) is a rare form of diabetes. FCPD is one of the two forms of malnutrition related diabetes mellitus (MRDM), the other one being protein deficient diabetes mellitus (PDDM). Fibrocalculus pancreatic diabetes was introduced for this form of diabetes by the World Health Organization study group report on diabetes. Several case reports of FCPD have been described in literature from tropical, poverty striken African and Asian countries for over 50 years. In India most cases are reported from Southern and Eastern India specifically from Kerala, Chennai and Odisha. From Jharkhand it is not reported.

Empirical characterisation of ranges of mainstream smoke toxicant yields from contemporary cigarette products using quantile regression methodology

Approximately 100 toxicants have been identified in cigarette smoke, to which exposure has been linked to a range of serious diseases in smokers. Smoking machines have been used to quantify toxicant emissions from cigarettes for regulatory reporting. The World Health Organization Study Group on Tobacco Product Regulation has proposed a regulatory scenario to identify median values for toxicants found in commercially available products, which could be used to set mandated limits on smoke emissions. We present an alternative approach, which used quantile regression to estimate reference percentiles to help contextualise the toxicant yields of commercially available products with respect to a reference analyte, such as tar or nicotine. To illustrate this approach we examined four toxicants (acetone, N′-nitrosoanatabine, phenol and pyridine) with respect to tar, and explored International Organization for Standardization (ISO) and Health Canada Intense (HCI) regimes. We compared this approach with other methods for assessing toxicants in cigarette smoke, such as ratios to nicotine or tar, and linear regression. We concluded that the quantile regression approach effectively represented data distributions across toxicants for both ISO and HCI regimes. This method provides robust, transparent and intuitive percentile estimates in relation to any desired reference value within the data space.

Longitudinal study of long-term smoking behaviour by biomarker-supported determination of exposure to smoke

BackgroundLong-term studies of smokers who switch to lower nicotine yield cigarettes have been identified by the World Health Organization Study Group TobReg and the US Food and Drug Administration as one key area where new knowledge is required to guide science based regulation. The limited number of long-term switching studies have concluded that smokers who switch to lower nicotine yield cigarettes show evidence of partial compensation. Since the European Union tobacco product directive of 2001 introduced tar and nicotine yield ceilings, there has been no long-term observational switching study. To address the limitations of previous studies where smokers were forced switched for relatively short durations, we plan to undertake a long-term study of spontaneous switching which is appropriately powered and includes non-switchers as a control group.Methods/designHealthy adult smokers aged 21–64 years will be enrolled into this 5-year non-residential, multicentre study across 10 cities in Germany. They will be assessed at 10 timepoints with 6 month intervals during which inclusion criteria will be reassessed and spent cigarette filter tips, saliva and 24 h urine samples will be collected. These samples will be used to determine average daily cigarette consumption, estimate mouth-level exposure to tar and nicotine and measure selected biomarkers of exposure, respectively. Spontaneous changes in subjects’ preferred cigarette products and any consequent change in tar or nicotine yield will be monitored. Subjects will be required to complete questionnaires on quality of life, smoking behaviours, smoking-related sensory attributes and recent life changes.DiscussionThe planned study is anticipated to contribute to understanding smokers’ behaviours and their consequent exposure to smoke constituents. It will also allow assessment of compensatory changes in their behaviour following spontaneous switching of cigarette product smoked. Data from this study are expected to provide insights into study design and conduct for non-clinical assessment of smokers’ exposure as part of post marketing surveillance programmes.Trial registrationCurrent Controlled Trials Database reference ISRCTN95019245.

Tobacco Smoke–Related Health Effects Induced by 1,3-Butadiene and Strategies for Risk Reduction

1,3-Butadiene (BD) is a smoke component selected by the World Health Organization (WHO) study group on Tobacco Product Regulation (TobReg) for mandated lowering. We examined the tobacco smoke–related health effects induced by BD and possible health impacts of risk reduction strategies. BD levels in mainstream smoke (MSS) from international and Canadian cigarettes and environmental tobacco smoke (ETS) were derived from scientific journals and international government reports. Dose-response analyses from toxicity studies from government reports were evaluated and the most sensitive cancer and noncancer endpoints were selected. The risks were evaluated by taking the ratio (margin of exposure, MOE) from the most sensitive toxicity endpoint and appropriate exposure estimates for BD in MSS and ETS. BD is a good choice for lowering given that MSS and ETS were at levels for cancer (leukemia) and noncancer (ovarian atrophy) risks, and the risks can be significantly lowered when lowering the BD concentrations in smoke. Several risk reduction strategies were analyzed including a maximum level of 125% of the median BD value per milligram nicotine obtained from international brands as recommended by the WHO TobReg, tobacco substitute sheets, dual and triple carbon filters, and polymer-derived carbon. The use of tobacco substitute sheet with a polymer-derived carbon filter resulted in the most significant change in risk for cancer and noncancer effects. Our results demonstrate that MOE analysis might be a practical way to assess the impact of risk reduction strategies on human health in the future.

Editor's Choice

Editor's Choice

Letter from the Editor

Basic & Clinical Pharmacology & ToxicologyVolume 111, Issue 6 p. 361-361 Letter from the EditorFree Access Letter from the Editor First published: 14 November 2012 https://doi.org/10.1111/bcpt.12030AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat The three organizations, the International Union of Basic and Clinical Pharmacology (IUPHAR), the Council for International Organizations of Medical Sciences (CIOMS) and the World Health Organization (WHO), have recently published a joint position paper 1 on clinical pharmacology in health care, teaching and research. It is an updated and edited version of a similar position paper 2 published in Basic & Clinical Pharmacology & Toxicology in July 2010 in connection with the 16th World Congress on Basic and Clinical Pharmacology in Copenhagen. The new position paper can be downloaded from the website of CIOMS: www.cioms.ch. The ambition is that the document will set the scene for the discipline in the first half of the 21st century in accordance with the concepts of an earlier WHO report published as long ago as in 1970 3. As the Editor-in-Chief of BCPT has been deeply involved in writing the position paper, it will not be reviewed here. The aim of this letter is simply to draw the attention of the readers of BCPT to its existence. References 1Abernethy D, Birkett D, Brøsen K, Cascorbi I, Gustafsson LL, Hoppu K et al. Clinical Pharmacology in health care, teaching and research. Edited by: M Orme, F Sjöqvist, D Birkett 2012. Available on www.cioms.ch 2Birkett D, Brøsen K, Cascorbi I, Gustafsson LL, Maxwell S, Rago L et al. Clinical pharmacology in research, teaching and health care: considerations by IUPHAR, the International Union of Basic and Clinical Pharmacology. Basic Clin Pharmacol Toxicol 2010; 107: 531– 59. 3 World Health Organization, Clinical pharmacology. Scope, organization, training. Report of a WHO study group. World Health Organ Tech Rep Ser 1970; 446: 5– 21. Volume111, Issue6December 2012Pages 361-361 ReferencesRelatedInformation

The Variable Presentations and Broadening Geographic Distribution of Hepatic Fascioliasis

We report 2 unrelated cases of hepatic fascioliasis in travelers returning to the United States from Africa and the Middle East. The first case presented with acute infection. Prominent clinical features included abdominal pain, elevated liver transaminases, serpiginous hepatic lesions, pericapsular hematoma, and marked peripheral eosinophilia. The second case was diagnosed in the chronic stage of infection and presented with right upper quadrant abdominal pain, cystic hepatic lesions, and an adult fluke in the common bile duct. We review the life cycle of Fasciola species, the corresponding clinical features during the stages of human infection, diagnostic methods, and the evolving understanding of the epidemiology of human fascioliasis, particularly emphasizing fascioliasis in African countries.

Use of the precautionary principle in the debate about emissions limits: a cautionary note

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A letter from Nigel Gray

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Mandated lowering of toxicants in cigarette smoke: a description of the World Health Organization TobReg proposal

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Are universal standards for optimal infant growth appropriate? Evidence from a Hong Kong Chinese birth cohort

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Can the WHO criteria for diagnosing osteoporosis be applied to calcaneal quantitative ultrasound?

With the increasing number of quantitative ultrasound (QUS) devices in use worldwide it is important to develop strategies for the clinical use of QUS. The aims of this study were to examine the age-dependence of T-scores and the prevalence of osteoporosis using the World Health Organization Study Group criteria for diagnosing osteoporosis and to examine the T-score threshold that would be appropriate to identify women at risk of osteoporosis using QUS. Two groups of women were studied: (i) 420 healthy women aged 20-79 years with no known risk factors associated with osteoporosis; (ii) 97 postmenopausal women with vertebral fractures. All subjects had dual-energy X-ray absorptiometry (DXA) measurements of the spine and hip and QUS measurements on three calcaneal ultrasound devices (Hologic Sahara, Hologic UBA575+, Osteometer DTUone). A subgroup of 102 (76 on the DTUone) healthy women aged 20-40 years was used to estimate the young adult mean and SD for each QUS and DXA measurement parameter to calculate T-scores. The age-related decline in T-scores for QUS measurement parameters was half the rate observed for the bone mineral density (BMD) measurements. The average T-score for a woman aged 65 years was -1.2 for QUS measurements and -1.75 for the BMD measurements. When osteoporosis was defined by a T-score < or = -2.5 the prevalence of osteoporosis in healthy postmenopausal women was 17%, 16% and 12% for lumbar spine, femoral neck and total hip BMD respectively. When the same definition was used for QUS measurements the prevalence of osteoporosis ranged from 2% to 8% depending on which ultrasound device and measurement parameter was used. Four different approaches, based on DXA-equivalent prevalence rates of osteoporosis, were utilized to examine which T-score threshold would be appropriate for identifying postmenopausal women at risk of osteoporosis using QUS measurements. These ranged from -1.05 to -2.12 depending upon the approach used to estimate the threshold and on which QUS device the measurements were performed, but all were significantly lower than the threshold of -2.5 used for BMD measurements. In conclusion, the WHO threshold of T = -2.5 for diagnosing osteoporosis requires modification when using QUS to assess skeletal status. For the three QUS devices used in this study, a T-score threshold of -1.80 would result in the same percentage of postmenopausal women classified as osteoporotic as the WHO threshold for BMD measurements. Corresponding T-score thresholds for individual measurement parameters on the two commercially available devices were -1.61, -1.94 and -1.90 for Sahara BUA, SOS and estimated heel BMD respectively and -1.45 and -2.10 for DTU BUA and SOS respectively Additional studies are needed to determine suitable T-score thresholds for other commercial QUS devices.