World Health Organization Working Group Research Articles

Rapid advice guidelines for management of children with COVID-19.

In December 2019, an infectious disease, caused by a novel coronavirus, emerged in Wuhan City, China. The disease was later named coronavirus disease 2019 (COVID-19) and the virus causing it was named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid spread of COVID-19 worldwide has brought great challenges to local and global public health security and health systems. On March 12, 2020, the World Health Organization (WHO) declared the coronavirus outbreak a global pandemic and raised the risk of a global SARS-CoV-2 outbreak to “very high” (1-6). COVID-19, and its pathogen SARS-CoV-2, represent a novel infectious disease and all populations are therefore susceptible to infection. Its basic reproductive number R0 has been estimated at 3.3 (range 1.4 to 6.5), which is similar to SARS and much higher than Middle East respiratory syndrome (MERS) or influenza (7-10). By April 15, around two million confirmed cases had been reported over 200 countries worldwide. The exact number of patients under the age of 18 remains unknown, but their percentage among all cases is estimated to be less than 2% (11,12). Evidence indicates that the family cluster is the main source of COVID-19 infection for children (13). In contrast to adults, most infected children are asymptomatic or have only mild clinical manifestations. The existing COVID-19 clinical practice guidelines for public health policies have mostly focused on the prevention, diagnosis and treatment in adults, with little attention paid to children. Few of them are based on evidence from systematic reviews (14). Based on the above considerations, an international multidisciplinary working group developed this rapid advice guideline for management of children with COVID-19 using the methods and process proposed by the WHO and GRADE working group (15-17). We present the following article in accordance with the RIGHT reporting checklist (available at http://dx.doi.org/10.21037/atm-20-3754).

Parental education and the WHO neonatal G-6-PD screening program: a quarter century later.

Neonatal screening for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in any population with a male frequency >3-5%, combined with parental education regarding the dietary, environmental and sepsis-related triggers for hemolysis was recommended by the WHO (World Health Organization) Working Group in 1989. As the aim of identifying G-6-PD deficiency in the newborn period is to avert or detect extreme hyperbilirubinemia developing at home, before the development of kernicterus, the parental role in identifying evolving icterus was considered integral to any screening program. Now, a quarter century after publication of this report, severe bilirubin neurotoxicity associated with G-6-PD deficiency continues to be encountered worldwide. Screening programs have not been universally introduced but several national or regional maternal child health programs have implemented neonatal G-6-PD screening. Some reports detail the role of parental education, based on the above mentioned principles, through a variety of audio-visual materials. The paucity of randomized controlled trials or validated evidence to demonstrate the effectiveness of the contribution of parental education fails to meet the ideal testable evidence-based approach. However, our review of the cumulative experience and evidence currently available does supply certain information reflecting a positive impact of screening programs combined with parental input. We propose that the current information is sufficient to continue to support and apply the Working Group's recommendations. In order not to waste unnecessary time available, data may be used in lieu of randomized trials to continue to recommend screening programs, as suggested, in high-risk regions. If the incidence of kernicterus associated with G-6-PD deficiency is to be diminished, G-6-PD screening in combination with parental explanation may be one instance in which the consensus approach suggested by the WHO Working Group, rather than reliance on (nonexistent) evidence-based studies, should continue to be practiced.

Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

P. Fenaux1, D. Haase2, G. F. Sanz3, V. Santini4 & C. Buske5 on behalf of the ESMO Guidelines Working Group* Service d’Hematologie Clinique, Groupe Francophone des Myelodysplasies (GFM), Hopital St Louis (Assistance Publique, Hopitaux de Paris) and Paris 7 University, Paris, France; Clinics of Hematology and Medical Oncology, University Medicine, Goettingen, Germany; Department of Haematology, Hospital Universitario y Politecnico La Fe, Valencia, Spain; Functional Unit of Haematology, AOU Careggi, University of Florence, Firenze, Italy; Comprehensive Cancer Center Ulm, Institute of Experimental Cancer Research, University Hospital, Ulm, Germany

135: Values of TNF alpha in cystic fluid in odontogenic tumor depending on macrophage number in cystic wall

The aggressive behavior and high recurrence rate of odontogenic keratocyst suggests their neoplastic potential and prompted the World Health Organization Working Group to classify it as a benign tumor with odontogenic epithelium. Since, TNF- α is a pleiotropic cytokine, that is considered as a primary modifier of inflammatory and immune reaction in response to various inflammatory diseases and tumor as well, it is very interesting to analyzed their concentration in our type of tumor. We analyzed concentration of TNF- α in cystic fluid of 25 odontogenic keratocysts, confirmed by histopathology and obtained from patients undergoing surgery, under local anesthesia, and after aspiration of cystic fluid from non-ruptured cysts. TNF- α was determined by ELISA assay, using original instructions. Presence of inflammatory cells in peri-cystic tissues and macrophages was analyzed by immunohistochemistry, using monoclonal antibodies for detection of CD3, CD20, and CD68 cells on tissues section. Cell caunt was expressed as percentage of these cells of the total cell population. Degree of vascularisation and presence of macrophages was estimated by enumeration using light microscopy. Results shows that TNF- α is detectable in cysts fluid, but in low values in all investigated cyst (range from 20–50 pg/ml). All cysts have a similar concentration of TNF- α in cystic fluid, irrespective of the cystic wall thickness, protein concentration, the number of inflammed cells, degree of epithelium proliferation and presence of vascularisation having been analyzed histologically (Mann–Whitney U-test, p > 0.05). These results indicated that our type of tumor have a low level of TNF- α and low inflammation in comparison to other inflammatory cystic type in oral region, that have a much more elevated TNF- α level.

Anatomy of the Pain Centre waiting list at the Centre hospitalier de l'Université de Montréal (CHUM)

BackgroundWaiting list management at chronic pain clinics has become a serious problem throughout Canada. We analyzed the waiting list at the Centre hospitalier de l’Université de Montréal (CHUM) Pain Centre.MethodsThe present study is an observational, prospective study. We used a specifically designed survey questionnaire. Survey findings were analyzed with descriptive statistical methods.ResultsA total of 270 patients were contacted; only 146 were included. Of these, 93 were women and 53 men. The average age was 55.9 years. Fifty-two percent of the patients were referred by a medical specialist; 34% by family physicians; 3% for emergency; and 11% unknown. The mean for pain score was 6.7/10. Seventy-three percent were taking pain killers with an average improvement on their pain score of 52%. Ten percent of respondents were not taking any type of analgesic medication, while 17% were taking over-the-counter drugs. Fifty-three percent of the patients had been suffering from chronic pain for 5 years or less, while 10% had been suffering and awaiting specialized pain treatment for more than 20 years.ConclusionOur data suggests that accessibility to specialized health care is not the sole obstacle to the timely and effective management of chronic pain. Seventy-three percent of the patients were taking some form of pharmaceutical treatment for pain and reported an average improvement rate of 52% on their pain score under medication. Such inconsistency may be attributable to patients’ lack of compliance with their treatment. The World Health Organization Working Group recommended in chronic patients a novel approach to health care, based on patient therapeutic education. Our results show that patients need to acquire self-management skills regarding their chronic conditions.

A Response to the Comments by Boister and McGrady

The authors contend Neil Boister’s and Benn McGrady’s arguments for situating a treaty against the illegal trade in counterfeit medicine under the auspices of the United Nations Office of Drugs and Crime (UNDOC), and update readers on developments, since the publication of their earlier paper proposing the creation of such a treaty, at theWorld Health Organization (WHO). We thank Professors Boister and McGrady for their contribution on achieving a treaty against counterfeit medicines. In this reply, we both respond to their argument for situating such a treaty under the auspices of the UN Office of Drugs and Crime (UNODC) c a proposal we consider to be on balance a poor idea c and update readers on the latest developments at the World Health Organization (WHO).We remain convinced that WHO is, for now, still the best institution under which to negotiate and achieve a treaty for improving the quality of medicines. But first, we must provide an update on an important issue of nomenclature. Our paper referred to deliberately false medicines as ‘counterfeit’ medicines. That was theWHO-approved term for about two decades, but it is now obsolete, after a decision in March 2011 by a WHO Working Group to reject it. * Associate Professor in the Faculties of Law and Medicine, University of Ottawa, Canada. [aattaran@uottawa.ca] ** Legatum Fellow in Global Prosperity, American Enterprise Institute, Washington DC, USA.

Health care provider obligations in caring for patients with tuberculosis

It is well acknowledged that physicians and other health care providers have an obligation to provide clinical care to their patients even under occasionally difficult circumstances. However, the exact degree and extent of that obligation, and the various scenarios under which it might be lessened or even cease to exist, have recently become the focus of much discussion and debate. The reason for this emerging debate is twofold: the recent occurrence of pandemic viruses such as severe acute respiratory syndrome and H1N1, and the emergence of highly resistant strains of infectious pathogens such as multi and extensively drug-resistant tuberculosis (TB). Health care providers have been asked to place themselves at risk to an extent many did not foresee when they chose to enter their profession, and many have done so under difficult conditions, often without adequate supplies and support. The present article explores the ethical obligations as well as the reciprocal rights of health care providers who are caring for patients with TB, with a particular focus on drug-resistant strains of the bacterium. It is a condensed version of a World Health Organization (WHO) Working Paper prepared for the WHO Working Group on Ethics and Tuberculosis.

Pathodiagnostic parameters for meningioma grading

Meningiomas are usually slow-growing benign tumors, for which complete removal can be difficult and recurrence is an issue. In this study the relationship between pathodiagnostic parameters, histological grade, and MIB-1 monoclonal antibody expression in meningioma diagnosed over 10 years in Shohada Hospital, Tehran, was assessed. All cases were re-evaluated according to the latest World Health Organization (WHO) Classification. Between January 1997 and December 2006, a total of 4885 intracranial tumors were diagnosed at Shohada Hospital, 378 (7.74%) of which were meningiomas. All slides stained with hematoxylin and eosin were reviewed by two independent pathologists and all the diagnoses reconfirmed; histological anaplasia was classified according to the grading of the WHO Working Group 2000 as benign (Grade I), atypical with incipient signs of anaplasia (Grade II), or overtly anaplastic (Grade III). The mean age of patients with meningiomas was 49.11 ± 12.99 years (range 6–78 years, median = 50); females outnumbered males by a ratio of 1.7 to 1. Presenting symptoms were headache/vertigo (66.7%) and epilepsy (28.5%). Convexity meningiomas were most common, followed by meningiomas of the sphenoid ridge and cerebellopontine angle. There was no relationship between the location of the tumor and the histopathological features. The association between mitotic rate, increased cellularity, nucleo-cytoplasmic ratio, and sheet-like spreading was especially strong. Histopathological study of completely resected meningiomas showed that loss of architecture, frequent mitotic figures, a high cellularity, increased nucleo-cytoplasmic ratio, a prominent nucleolus, brain invasion, and necrosis were correlated with the grade of the meningiomas. Overall, the mitotic count was the most important marker for tumor grade.

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

Preventing initiation of tobacco product use, promoting cessation of tobacco use, and protecting the public from exposure to second hand smoke are recognised by the World Health organization (WHO) Framework...

Workgroup Report: Developing Environmental Health Indicators for European Children: World Health Organization Working Group

A working group coordinated by the World Health Organization developed a set of indicators to protect children’s health from environmental risks and to support current and future European policy needs. On the basis of identified policy needs, the group developed a core set of 29 indicators for implementation plus an extended set of eight additional indicators for future development, focusing on exposure, health effects, and action. As far as possible, the indicators were designed to use existing information and are flexible enough to be developed further to meet the needs of policy makers and changing health priorities. These indicators cover most of the priority topic areas specified in the Children’s Environment and Health Action Plan for Europe (CEHAPE) as adopted in the Fourth Ministerial Conference on Health and Environment in 2004, and will be used to monitor the implementation of CEHAPE. This effort can be viewed as an integral part of the Global Initiative on Children’s Environmental Health Indicators, launched at the World Summit on Sustainable Development in 2002.

Columnar Cell Lesions and Flat Epithelial Atypia of the Breast

Lesions of the breast characterized by enlarged terminal duct lobular units lined by columnar epithelial cells are being encountered increasingly in breast biopsies performed because of mammographic microcalcifications. Some of these lesions feature banal columnar cells in either a single layer (columnar cell change) or showing stratification and tufting but without complex architectural patterns (columnar cell hyperplasia). In other columnar cell lesions, the lining cells exhibit cytologic atypia, most commonly of the low-grade, monomorphic type. Such lesions were included among lesions originally categorized by Azzopardi as “clinging carcinoma” (monomorphic type), and were more recently included among lesions designated “flat epithelial atypia” (FEA) by the World Health Organization Working Group on Tumors of the Breast. The role of columnar cell lesions and, in particular, FEA in breast tumor progression is still emerging. FEA commonly coexists with well-developed examples of atypical ductal hyperplasia, low-grade ductal carcinoma in situ, and tubular carcinoma. These findings, in conjunction with the results of recent genetic studies, suggest that FEA is a neoplastic lesion that may represent either a precursor to or the earliest morphological manifestation of DCIS. However, the few available clinical outcome studies suggest that the risk of progression of FEA to invasive cancer is extremely low, supporting the notion that categorizing such lesions as “clinging carcinoma” and managing them as if they were fully developed DCIS will result in overtreatment of many patients. Additional studies are needed to better understand the biological nature and clinical significance of these lesions.

Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife.

An expert meeting was organized by the World Health Organization (WHO) and held in Stockholm on 15-18 June 1997. The objective of this meeting was to derive consensus toxic equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and dioxinlike polychlorinated biphenyls (PCBs) for both human, fish, and wildlife risk assessment. Based on existing literature data, TEFs were (re)evaluated and either revised (mammals) or established (fish and birds). A few mammalian WHO-TEFs were revised, including 1,2,3,7,8-pentachlorinated DD, octachlorinated DD, octachlorinated DF, and PCB 77. These mammalian TEFs are also considered applicable for humans and wild mammalian species. Furthermore, it was concluded that there was insufficient in vivo evidence to continue the use of TEFs for some di-ortho PCBs, as suggested earlier by Ahlborg et al. [Chemosphere 28:1049-1067 (1994)]. In addition, TEFs for fish and birds were determined. The WHO working group attempted to harmonize TEFs across different taxa to the extent possible. However, total synchronization of TEFs was not feasible, as there were orders of a magnitude difference in TEFs between taxa for some compounds. In this respect, the absent or very low response of fish to mono-ortho PCBs is most noticeable compared to mammals and birds. Uncertainties that could compromise the TEF concept were also reviewed, including nonadditive interactions, differences in shape of the dose-response curve, and species responsiveness. In spite of these uncertainties, it was concluded that the TEF concept is still the most plausible and feasible approach for risk assessment of halogenated aromatic hydrocarbons with dioxinlike properties.

Toxic Equivalency Factors (TEFs) for PCBs, PCDDs, PCDFs for Humans and Wildlife

An expert meeting was organized by the World Health Organization (WHO) and held in Stockholm on 15-18 June 1997. The objective of this meeting was to derive consensus toxic equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and dioxinlike polychlorinated biphenyls (PCBs) for both human, fish, and wildlife risk assessment. Based on existing literature data, TEFs were (re)evaluated and either revised (mammals) or established (fish and birds). A few mammalian WHO-TEFs were revised, including 1,2,3,7,8-pentachlorinated DD, octachlorinated DD, octachlorinated DF, and PCB 77. These mammalian TEFs are also considered applicable for humans and wild mammalian species. Furthermore, it was concluded that there was insufficient in vivo evidence to continue the use of TEFs for some di-ortho PCBs, as suggested earlier by Ahlborg et al. [Chemosphere 28:1049-1067 (1994)]. In addition, TEFs for fish and birds were determined. The WHO working group attempted to harmonize TEFs across different taxa to the extent possible. However, total synchronization of TEFs was not feasible, as there were orders of a magnitude difference in TEFs between taxa for some compounds. In this respect, the absent or very low response of fish to mono-ortho PCBs is most noticeable compared to mammals and birds. Uncertainties that could compromise the TEF concept were also reviewed, including nonadditive interactions, differences in shape of the dose-response curve, and species responsiveness. In spite of these uncertainties, it was concluded that the TEF concept is still the most plausible and feasible approach for risk assessment of halogenated aromatic hydrocarbons with dioxinlike properties.

Reports on surveillance of antimicrobial resistance in individual countries.

In preparation for the meeting of the World Health Organization Working Group on Monitoring and Management of Bacterial Resistance to Antimicrobial Agents, representatives of 10 countries were asked to provide brief reports on the status of surveillance in their countries. Some gave extensive information on the methods used to test susceptibility of nosocomial pathogens to a variety of antibiotics; some described in detail the network of reference laboratories available to hospitals and individual clinicians for monitoring, identifying, and testing infectious agents; others chose to describe how their countries deal with the resistance of the most frequently isolated pathogen to a commonly used drug. The following summary of these reports shows the broad range of problems encountered and solutions undertaken by these 10 countries in dealing with the increasingly alarming problem of bacterial resistance to antimicrobial agents.

Health criteria for radon indoors

Reports on the deliberations of a World Health Organization working group which met in Eilat, Israel, in 1993 to discuss “risk assessment values”, and a unified approach to the control of human exposure to radon, which is known to cause lung cancer in human beings. Summarizes the working group′s conclusions and recommendations.

The world health organization monica project (monitoring trends and determinants in cardiovascular disease): A major international collaboration

A World Health Organization Working Group has developed a major international collaborative study with the objective of measuring over 10 years, and in many different populations, the trends in, and determinants of, cardiovascular disease. Specifically the programme focuses on trends in event rates for validated fatal and non-fatal coronary heart attacks and strokes, and on trends in cardiovascular risk factors (blood pressure, cigarette smoking and serum cholesterol) in men and women aged 25–64 in the same defined communities. By this means it is hoped both to measure changes in cardiovascular mortality and to see how far they are explained; on the one hand by changes in incidence mediated by risk factor levels; and on the other by changes in case-fatality rates, related to medical care. Population centres need to be large and numerous; to reliably establish 10-year trends in event rates within a centre 200 or more fatal events in men per year are needed, while for the collaborative study a multiplicity of internally homogeneous centres showing differing trends will provide the best test of the hypotheses. Forty-one MONICA Collaborating Centres, using a standardized protocol, are studying 118 Reporting Units (sub-populations) with a total population aged 25–64 (both sexes) of about 15 million