WHO Expert Committee Research Articles

Updating the WHO Model Lists of Essential Medicines to promote global access to the most cost-effective and safe medicines for mental disorders

IntroductionSince its first publication in 1977, the World Health Organization’s (WHO) Model List of Essential Medicines (EML) has guided the national procurement of medicines deemed essential to inform public health policy worldwide. Aiming to include the most effective, safe, and cost-effective medicines for priority conditions, WHO updates the EML every two years. However, over the past 45 years, updates to the mental health section of the EML have been infrequent, mostly involving the addition of individual medicines. A comprehensive revision of the entire section was never attempted.ObjectivesThe aim of this project was to update the mental health section of the EML to identify the most effective and safest medicines for mental disorders in the light of the most up-to-date evidence base.MethodsA series of nine evidence-based applications were submitted to the WHO Expert Committee on the Selection and Use of Essential Medicines in December 2022, recommending a substantial revision of the entire mental health section.ResultsAll of our applications were accepted by the WHO Expert Committee. For psychotic disorders, aripiprazole, olanzapine, paliperidone, and quetiapine were added as therapeutic alternatives to risperidone; short-acting intramuscular chlorpromazine was replaced by short-acting intramuscular olanzapine; first-generation antipsychotics were limited to oral haloperidol and chlorpromazine. For bipolar disorder, the list now includes second-generation antipsychotics such as quetiapine, aripiprazole, olanzapine, and paliperidone. Tricyclic antidepressants for depressive disorders were limited to amitriptyline alone. Treatment options for anxiety and obsessive-compulsive disorder are now expanded to include SSRIs. For anxiety disorders, diazepam and lorazepam became the only benzodiazepines recommended, with the specific caveat that they should only be used for short-term emergency treatment of acute and severe anxiety symptoms. Finally, chlorpromazine and haloperidol are no longer considered essential medications for psychotic disorders in children under 13 years of age.ConclusionsThe WHO released the 23rd EML in July 2023. After decades of minimal and inconsistent updates, groundbreaking changes have been made to its mental health section. The updated mental health section provides a compelling opportunity to improve the quality of medicine selection at the country level, with the goal of increasing the availability of the safest and most effective psychotropic medicines worldwide.Disclosure of InterestNone Declared

Clinical case of acute hepatitis in a patient with ascariasis

Helminthiases are fairly widespread human parasitic diseases caused by various lower worms - helminths. In the Russian Federation, more than 4.5 million cases of helminthiasis were registered in 2016. According to the WHO Expert Committee, ascariasis affects about 900 million people in the world every year, most of whom are children of preschool and school age. In the Russian Federation, 24,115 cases of ascariasis were registered in 2015. The true prevalence of helminthiasis is much higher. In recent decades, there has been an increase in and manifestation of new helminth infestations as a result of changes in economic and socio-economic conditions, increased migration, and the introduction of helminths, common in countries with tropical and subtropical climates, to Russia. The possibility of a patient having one or another type of helminthiasis is practically not taken into account in clinical practice, which leads to incorrect diagnosis, the development of complications of the disease, and its transition to a chronic form. As a rule, helminthiases are relatively asymptomatic, but in some cases their local manifestations come to the fore clinically and the disease occurs under the guise of infectious and non-infectious diseases.

Availability of access, watch, and reserve (AWaRe) group of antibiotics in community pharmacies located close to a tertiary care hospital in Lalitpur, Nepal.

The access, watch, and reserve (AWaRe) classification of antibiotics was developed in 2019 by the WHO Expert Committee on the Selection and Use of Essential Medicines as a tool to support antibiotic stewardship efforts at local, national, and global levels. The objectives of this study were to assess the availability of antibiotics as per WHO AWaRe classification at community pharmacies located around a tertiary care hospital in Lalitpur and to compare these antibiotics with the national essential medicine list of Nepal. The cross-sectional study was conducted at community pharmacies located within a two-kilometer radius of a teaching hospital from August to November 2022. A total of 82 community pharmacies registered with the Nepal Chemist and Druggists Association and the Department of Drug Administration were studied. Data was collected using a standard proforma containing the names of the antibiotics classified as per the WHO's AWaRe classification. Access group of antibiotics, Ampicillin, (82;100%), Amoxycillin, (82;100%), Flucloxacillin, (82;100%), and Metronidazole, (82;100%) were available in all community pharmacies. Results from the watch group showed that Azithromycin, (80; 97.6%) was available in all pharmacies followed by Cefixime, (80; 97.6%), Ciprofloxacin, (73; 89%), Levofloxacin, (74; 90.2%)and Ofloxacin, (74; 90.2%). Linezolid, (24; 29.3%) was the most common antibiotics available from the reserve group of antibiotics. Colistin was the second commonly available antibiotic. The most available antibiotic from the not recommended group were Ampicillin/Cloxacillin (82; 100%), followed by Piperacillin/Sulbactam, (39; 47.6%). There were differences in the classification of antibiotics between the WHO AWaRe list and the Essential Medicines list of Nepal in terms of numbers of antibiotics listed. Antibiotics from the not recommended and reserve groups were commonly available in community pharmacies. The implementation of antibiotic guidelines should be emphasized along with strict monitoring of the sale of antibiotics without a prescription in community pharmacy settings.

Deep Sequencing and Molecular Characterisation of BK Virus and JC Virus WHO International Reference Materials for Clinical Diagnostic Use.

Reactivation of JC and BK polyomaviruses during immunosuppression can lead to adverse clinical outcomes. In renal transplant recipients, BKV-associated nephropathy can result in graft loss, while in patients with autoimmune disorders, prolonged immunomodulatory drug use can cause rare onset of progressive multifocal leukoencephalopathy due to JCV reactivation. In such patients, accurate BK and JC viral load determinations by molecular technologies are important for diagnosis and clinical management; however, comparability across centres requires effective standardisation of diagnostic molecular detection systems. In October 2015, the WHO Expert Committee for Biological Standardisation (ECBS) established the 1st WHO International Standards (ISs) for use as primary-order calibrants for BKV and JCV nucleic acid detection. Two multi-centre collaborative studies confirmed their utility in harmonising agreement across the wide range of BKV and JCV assays, respectively. Previous Illumina-based deep sequence analysis of these standards, however, identified deletions in different regions, including the large T-antigen coding region. Hence, further detailed characterization was warranted. Comprehensive sequence characterisation of each preparation using short- and long-read next-generation sequencing technologies was performed with additional corroborative independent digital PCR (dPCR) determinations. Potential error rates associated with long-read sequencing were minimised by applying rolling circle amplification (RCA) protocols for viral DNA (circular dsDNA), generating a full validation of sequence identity and composition and delineating the integrity of full-length BK and JC genomes. The analysed genomes displayed subpopulations frequently characterised by complex gene re-arrangements, duplications and deletions. Despite the recognition of such polymorphisms using high-resolution sequencing methodologies, the ability of these reference materials to act to enhance assay harmonisation did not appear significantly impacted, based on data generated by the 2015 WHO collaborative studies, but highlights cautionary aspects of IS generation and commutability for clinical molecular diagnostic application.

CORRECTION OF CHANGES IN LIPID METABOLISM AND REDOX SYSTEM IN PATIENTS WITH STEMI IN THE SETTING OF INSULIN RESISTANCE

Myocardial infarction (STEMI) remains one of the most important problems of modern Cardiology both in Ukraine and worldwide due to its recalcitrant indices of incidence, disability and mortality. The prevalence of metabolic syndrome (MS) and DM2 in Ukraine is quite high, accounting for 20-28% in the general population and over 50% in certain demographics. In persons with abdominal obesity, metabolic syndrome and DM2, there is a 30% total risk of developing MI in the next 8 years, and their mortality rate is double thatof persons without metabolic disorders. The unfavorable prognosis in such patients is attributed to insulin resistance as an additional risk factor for CAD progression and the development of ACS, which determines the need to develop methods for correction of these abnormal processes.
 The aim of the research: to explore the efficacy of correcting the disorders of lipid profile and prooxidant/antioxidant system balance in patients with STEMI in a setting of insulin resistance and high risk of reperfusion complications by using dapagliflozin, a SGLT2 inhibitor.
 The methods of the research. The basis of the work has been underlain by the analysis of a comprehensive assessment and surgical treatment (percutaneous coronary intervention) in 73 patients with STEMI in the setting of insulin resistance in MS and DM2. The parameters of lipid profile and the activity of the components in the prooxidant/antioxidant system were determined by spectrophotometric methods; the absorbancy was measured on a Biomat 5 spectrophotometer (United Kingdom).The diagnosis of ACS was verified according to ESC Guidelines in the presence of a typical anginal attack, ACS-specific ECG changes with time (reciprocal ST displacement) and the signs of necrosis-resorption syndrome.The diagnosis was subsequently confirmed by the results of urgent coronary angiography. The diagnosis of MS and type 2 DM was made according to the recommendations of the WHO Expert Committee (2013) and the updated ADA/EASD consensus (2018).
 Results. In order to improve lipid profile and redox system balance in pre- and postoperative period, the patients were prescribed dapagliflozin at the dose of 10 mg/day, which allowed compensation of hyperglycemia, reduction of insulin resistance and stabilizing the activity of prooxidant/antioxidant system, preventing post-PCI reperfusion complications and stabilizing the clinical condition of comorbid patients in the postoperative period owing to a 40.4% reduction in the incidence of rhythm and conductivity disorders, and a 55.3% reduction in manifestations of acute heart failure. There has been a substantial reduction in free radical oxidation in the setting of dapagliflozin treatment, as suggested by a 1.3-fold reduction (р<0.05) in active products of thiobarbituric acid in the serum and a simultaneous restoration of functioning of enzymatic antioxidant systems, a 1.5-fold reduction (p<0.05) in the degree of superoxide dismutase blockage with an increased activity of catalase and ceruloplasmin.
 Conclusions. The use of dapagliflozin in pre- and postoperative patients with STEMI in the setting of insulin resistance and high surgical risk contributes to improvement of lipid metabolism and a significant reduction in the activity of free radical oxidation with restoration of functioning of enzymatic antioxidant systems in the body, which allows for a significant reduction in the incidence of rhythm and conduction disorders and the manifestations of acute heart failure.

Herb Stevia Rebaudiana’s Functionalities, Safety, and Applications: A Review

Herb Stevia rebaudiana extract, also known as sweetleaf, was originally discovered for its sweetening function. Researches show that this plant extract is embedded with multiple functionalities such as antioxidant, antidiabetics, anti-inflammation, and antimicrobial. This review article helps re-arrange the scientific affairs of those stevia extract’s functions. Sweetness indexes of steviol glycosides were summarized together for comparison while various in vitro, in vivo approaches were reviewed to quantify those functions’ capacities and to depict the related mechanism. The regulation of steviol glycoside compounds such as rebaudioside A was established by global authorities such as US Food and Drug Administration (FDA) and Joint FAO/ WHO Expert Committee (JECFA) to ensure the safety endorsement prior to commercialization. In applications, we first used sentiment analysis to catch a good command of the stevia-containing products’ market performance. Then, we investigated the product development progress of stevia-containing food products in the categories of beverage, bakery, dairy, and confectionery. Those stevia-containing food consumer goods can be acceptable by certain customers.

Stability analysis of the reference standard of <i>Mycoplasma arginini</i> strain G230 used for testing biologicals for mycoplasmas

The State Pharmacopoeia of the Russian Federation (Ph.Rus.) requires a preparatory evaluation of culture medium suitability using the reference standard (RS) of the Mycoplasma arginini G230 test strain in order to ensure reliable results when testing medicines for mycoplasmas using a microbiological (culture) method. The RS retains the stability of physico-chemical properties and the certified characteristic value (titre) for one year if stored under the specified temperature conditions (–20 ºC to –30 ºC). Deviations from this range and transportation in ambient conditions can alter the properties of the RS and consequently result in biologicals substandard in terms of mycoplasmas. Experts from the Reference Materials Committee of the International Organisation for Standardisation (ISO), the State System for Ensuring the Uniformity of Measurements, and the WHO Expert Committee on Biological Standardisation emphasise the need to study the stability of RSs not only under the specified long-term storage conditions, but also with short-term deviations from such conditions. The aim of the study was to analyse the stability of the M. arginini G230 test strain RS under the specified long-term storage conditions and with short-term exposure to elevated temperatures. Materials and methods: the study used the RS of M. arginini G230 by the Scientific Centre for Expert Evaluation of Medicinal Products and culture media and solutions required per the Ph.Rus. general chapter on mycoplasma tests (OFS.1.7.2.0031.15). The stability of RS’s characteristics, including the certified value (titre), was determined using Ph.Rus. methods. The experiment involved two testing regimes with short-term exposure to elevated temperatures. Control samples were stored at –20±2 °С. Statistical data processing was carried out by the serial dilution method using McCrady’s table with the calculation of the arithmetic mean of the most probable number (MPN) for the limiting dilution (titre). Results: as demonstrated in the study under the specified conditions, the RS retains its characteristics for a period exceeding its shelf life (for up to 16 months). The main characteristics of the RS remain stable after 30-day exposure to elevated temperatures (25±2 ºC and 37±2 ºC). The certified value (titre) of the RS decreases after exposure to 37±2 ºC for 10 and 30 days. Conclusions: the study proved the possibility of storing and transporting the RS at a temperature lower than 25±2 ºC for up to 30 days with no subsequent changes to the quality within the 1-year shelf life. The conditions of 37±2 ºC cannot be used for the purpose.

A survey of Eutylone Prevalence in New Zealand during 2020 and 2021

This study provides an insight into the prevalence of eutylone in New Zealand by analysis of the post-mortem forensic toxicology cases over the period 2020 and 2021, as well as analysis of suspected drug items collected from three music festivals between December 2020 and February 2021. Eutylone, also known as bk-EBDB or n-ethylbutylone, is a synthetic cathinone that has no known therapeutic use. In New Zealand it is sold recreationally as an alternative to methylendioxymethamphetamine (MDMA) and has increasingly been found as an adulterant or substitution substance in MDMA samples. Eutylone is known to cause harm and has been associated with fatalities [World Health Organization. “WHO Expert Committee on Drug Dependence: forty-fourth report.” (2022)]. In many cases, users are unaware that the eutylone is present believing they are taking MDMA. ESR undertakes post-mortem forensic toxicology casework for the whole of New Zealand. We investigated the post-mortem cases received during 2020 and 2021 for eutylone and investigated trends. In addition to the post-mortem forensic toxicology cases, ESR analysed 656 drug samples from three music festivals held between December 2020 and February 2021 for the presence of drugs including eutylone. The post-mortem blood samples were analysed using liquid chromatography with time of flight mass spectrometry (LC-TOFMS) for eutylone. Eutylone was detected in three cases during 2020 and in twelve (12) cases during 2021. Of the 12 cases from 2021, ten decedents were male, nine cases had a known cause of death (e.g. hanging), two cases were at or just after a music festival and two cases appeared to be drug overdoses where multiple drugs were involved. Eutylone was the only drug detected in three of the cases (all with a known cause of death). When other drugs were involved the most common were methamphetamine ( n = 4), MDMA ( n = 3), alcohol ( n = 3) and cannabis ( n = 3). For the 656 samples analysed from the three music festivals MDMA and eutylone were detected in 33% and 32% of the samples, respectively. This can be contrasted with a previous survey from December 2018 to March 2019 that found MDMA in 64% of samples and eutylone detected in less than 1% of the samples. If a mixture was present in a sample, it was common for it to contain both eutylone and MDMA. There was a significant increase in eutylone detections both in blood samples from post-mortem forensic toxicology casework and in seized drug samples over the time period studied, with associated increases in the harm, including deaths, associated with the drug use. It has been postulated that this trend was influenced by factors such as the limited supply of MDMA in New Zealand due to law enforcement activity including a large MDMA seizure prior to the survey period for the music festivals, COVID-19 restrictions and the use of eutylone as an adulterant or replacement drug.

International Legal Aspects of Control of Trafficking in New Psychoactive Substances

Aim. To analyze relevant provisions of the main national and international regulatory legal acts in the field of monitoring and control of new potentially dangerous substances.Tasks. To study the current legal regulation of legal and illicit trafficking of new psychoactive substances in the Russian Federation and the EAEU states. To examine new amendments in the legislation of the European Union regulating the substances traffic control and illicit traffic countering. To provide an overview of the procedures of new psychoactive substances scheduling under the International Drug Control Conventions. To formulate proposals for improving the national and international anti-drug legislation.Methods. The methods of logical and comparative legal analysis, as well as the legal prediction method have been used in this article.Results. The legislation of the EAEU countries in the field of the control of the legal and illicit trafficking of new psychoactive substances needs to be improved and harmonized. The substances scheduling procedures under the international drug control conventions in the EU and the UN are very difficult multi-stage and excessively long. The timing of adoption of new regulatory acts certainly does not correspond to the potential danger of uncontrolled trafficking of new potentially dangerous psychoactive substances for public health.Conclusion. The penalties under Art. 234.1 of the Russian Federation Criminal Code “Illicit trafficking of potentially dangerous psychoactive substances” should be toughened. The legal procedure for forming the state Register of new psychoactive substances must be changed. In the EAEU countries, it should be necessary to make agreement at the interstate level about a uniform approach to the introduction and content of criminal justice responses to the illicit trafficking of new psychoactive substances. In the EU countries and in the frame of the UN, the scheduling procedure under international drug control should be changed regarding new psychoactive substance. All such substances of this kind should be included in a Special Annex for which certain agreed control measures would be prescribed, with the possibility of subsequent expert evaluation of the potential danger of the substance to individual and public health. These established control measures in the fut ure might be toughened or reduced based on the WHO Expert Committee on Drug Dependence critical review and the Commission on Narcotic Drugs (CND) position.

BLOOD PRESSURE IN RELATION TO BODY MASS INDEX AMONG THE MONPA: ALTITUDINAL DIFFERENCE

Background and Objectives: Many studies have well documented that there is a positive association between body mass index and systolic blood pressure as well as body mass index and diastolic blood pressure. The present study examines body mass index and blood pressure in two Arunachal Monpa populations namely the Dirang (low altitude population) and Tawang (high altitude population) Monpa. Material and Methods: Healthy, 303 adult Dirang (Male: 146, Female: 157) and 472 Tawang (Male: 210, Female: 262) Monpa were randomly selected. The body mass index cut-off value for Asian people was considered as recommended by the WHO expert group (WHO 2000). While blood pressure values were classified according to the WHO expert committee (WHO 1996). Results: This study reveals a positive relationship between body mass index and blood pressure. Mean SBP and DBP both were considerably higher among the Dirang than that of the Tawang Monpa. Blood pressure values were correlated more with body mass index among the Tawang Monpa than their counterparts. Conclusion: Present study is indicative of altitudinal stresses on biological traits in highlander Tawang Monpas than that of the Dirang Monpas.

International collaborative study to evaluate and calibrate two recombinant L chain Ferritin preparations for use as a WHO International Standard.

To evaluate and calibrate two candidate preparations for the 4th International Standard for Ferritin (Human, Recombinant) (codes: 19/118 and 19/162) against the 3rd International Standard for Ferritin (Human, Recombinant) (code: 94/572), and three serum commutability samples in an international collaborative study involving 12 laboratories in nine countries. Eleven of the 12 participating laboratories performed Ferritin quantitation using automated assay platforms and one laboratory used a manual ELISA kit. There was better overall agreement between all laboratories and between assay methods for the potency of preparation 19/118 than for preparation 19/162. The overall geometric mean potency (from all methods) of the candidate 4th International Standard, 19/118, was 10.5 µg/ampoule, with inter-laboratory variability, expressed as % geometric coefficient of variation (GCV), of 4.7%. Accelerated stability studies have predicted both 19/118 and 19/162 to be very stable for long term storage at-20°C. The candidate 4th International Standard for Ferritin (Human, Recombinant) (19/118) has been shown to be immunologically similar to the 3rd International Standard for Ferritin (Human, Recombinant) (94/572). It was recommended to and accepted by the WHO Expert Committee on Biological Standardization that 19/118 be established as the 4th International Standard for Ferritin (Human, Recombinant) with an assigned potency of 10.5µg/ampoule and expanded uncertainty limits 10.2-10.8µg/ampoule (95% confidence; k=2.23).

WHO international standard for SARS-CoV-2 antibodies to determine markers of protection

Several studies have shown that neutralising antibody level is a good biomarker for the correlate of protection against SARS-CoV-2 infection.1–3 However, results from these studies are presented using assays that have not been calibrated using a common reference standard, making it difficult to define the exact level of neutralising antibodies required for protection and to compare with current and future studies. The most recent study4 is the only one we have identified that reports the neutralising antibody level using WHO international units by calibrating their neutralisation assays against the WHO international standard for SARS-CoV-2 immunoglobulin; the international standard was established by the WHO Expert Committee on Biological Standardization as a primary calibrant to harmonise the measurement of anti-SARS-CoV-2 antibodies and was made available in December, 2020 from the WHO Collaborative centre, the National Institute for Biological Standards and Control (NIBSC), UK.

Religion and the World Health Organization: an evolving relationship

Much has been written about WHO. Relatively little is known, however, about the organisation’s evolving relationship with health-related personal beliefs, ‘faith-based organisations’ (FBOs), religious leaders and religious communities (‘religious actors’)....

An affordable pneumococcal conjugate vaccine after 20 years

An affordable pneumococcal conjugate vaccine after 20 years

Comperative Study on the Intervention of ‘Spice ‘ Mixture (SM) Prepared by Natural Food Additives (NFA) Alone or Intervention of SM with Mind Calming Exercise in the Management on Female Obesity

Obesity has become huge health problem in the entire world. In Sri Lanka, the prevalence of obesity is estimated to be 20.3% in men and 36.5% in women in four provinces. Further, the highest prevalence rate in Western Province, especially in Colombo was estimated to be 32.2%, among adults. Obesity is associated with osteoarthritis, obstructive sleep apnea, gall stones, and hiatus hernia. In addition to this obesity is related to numerous other problems, such as menstrual and mental disorders and varicose vein etc. According to the concept of Unani four treatment modalities are there; they are known as Dieto therapy (Ilaj Bil Ghiza), Pharmaco therapy (Ilaj Bil Dawa), Regimental therapy (Ilaj Bit Tadbeer) and Surgery (Ilaj Bil Yad). Biomarkers such as Lipid profile (VLDL, LDL, HDL And Serum triglycerides), Haemoglobin percentage, SGPT and SC (Serum Creatinine) were considered. Blood sample analysis was performed at NATH (National Ayurvedic Teaching Hospital), Borella, National Diabetic Centre, Rajagiriya and Asiri Hospitals Ltd. According to Unani or Greco-Arabic medical concept, improper digestion may play a main role to cause obesity. Improper digestion was corrected by using a ‘spice’ mixture made by Natural Food Additives (NFA), which possesses the actions of carminative, digestive and strengthens the gastro-intestinal tract. The preparation of ‘spice’ mixture included Natural Food Additives (NFA). They are Cumin (Cuminum cyminum), Garlic (Allium sativum), Curry Leaves (Murraya koenigii), Ceylon Cinnamon (Cinnamomum zeylanicum) and Black Pepper (Piper nigram). Studies revealed that waist circumferences (WC) is closely linked to CV disease risk factors. Also, WHO Expert Committee on Obesity in Asian and Pacific populations suggested that revised cutoff points for WC: 90 cm for men and 80 cm for women to identify patients with abdominal obesity. South Asians are more prone to insulin resistance and dyslipidaemic state of abdominal obesity. Study concluded that the intervention of ‘spice’ mixture reduces obesity and the effective mind calm exercises would give more beneficial effect in weight reduction.

Establishment of transfusion-relevant bacteria reference strains for red blood cells.

Red blood cell concentrates (RBCC) are susceptible to bacterial contamination despite cold storage. A reliable evaluation of strategies to minimize the risk of RBCC-associated bacterial transmission requires the use of suitable reference bacteria. Already existing Transfusion-Relevant Bacteria Reference Strains (TRBRS) for platelet concentrates fail to grow in RBCC. Consequently, the ISBT TTID, Working Party, Bacterial Subgroup, conducted an international study on TRBRS for RBCC. Six bacterial strains (Listeria monocytogenes PEI-A-199, Serratia liquefaciens PEI-A-184, Serratia marcescens PEI-B-P-56, Pseudomonas fluorescens PEI-B-P-77, Yersinia enterocolitica PEI-A-105, Yersinia enterocolitica PEI-A-176) were distributed to 15 laboratories worldwide for enumeration, identification, and determination of growth kinetics in RBCC at days 7, 14, 21, 28, 35 and 42 of storage after low-count spiking (10-25CFU/RBCC). Bacterial proliferation in RBCC was obtained for most strains, except for S. marcescens, which grew only at 4 of 15 laboratories. S.liquefaciens, S.marcescens, P.fluorescens and the two Y.enterocolitica strains reached the stationary phase between days 14 and 21 of RBCC storage with a bacterial concentration of approximately 109 CFU/ml. L.monocytogenes displayed slower growth kinetics reaching 106 -107 CFU/ml after 42days. The results illustrate the importance of conducting comprehensive studies to establish well-characterized reference strains, which can be a tool to assess strategies and methods used to ameliorate blood safety. The WHO Expert Committee on Biological Standardization adopted the five successful strains as official RBCC reference strains. Our study also highlights the relevance of visual inspection to interdict contaminated RBC units.

Establishment of a WHO Reference Reagent for anti-Mullerian hormone

BackgroundThere is a need for a reference material to support the development and ensure the quality of immunoassays for human AMH. A batch of ampoules, coded 16/190, containing lyophilised recombinant AMH was evaluated in a WHO Collaborative Study. The aims of the study were to determine the AMH content in terms of the calibration of each immunoassay method, to predict long-term stability and to assess the suitability of the preparation to calibrate AMH immunoassays.MethodsStudy participants were asked to report the AMH content of specific dilutions of coded ampoules of 16/190 and a comparator preparation containing approximately half the AMH content. In each assay, participants also reported the AMH content of 22 patient samples to assess commutability. A robust all-laboratory geometric mean of the content estimates was determined using the laboratory geometric mean estimates. Commutability was assessed using a difference in bias approach. Stability was predicted by the measurement of thermally accelerated degradation samples.ResultsSeven laboratories performed twenty-one immunoassay method-platform combinations, sixteen of which provided data which met the validity criteria, giving a consensus geometric mean estimate of AMH content of 511 ng/ampoule (95% CI, 426–612, n = 16, GCV 42%) and a robust geometric mean of 489 ng/ampoule. By contrast, the GCV% for the all-laboratory geometric mean of the relative content estimates for the comparator sample to 16/190 was 12%. Commutability was assessed using 20 of the 22 representative patient samples. Of the valid assays, 16/190 was within the limits of acceptable commutability for 6 methods, partially commutable for a further 3 methods and non-commutable when measured by 7 methods. The preparation was predicted to be highly stable when stored at − 20 °C.ConclusionThe majority of methods met the validity criteria. Content estimates showed a high between-method variability, yet assays exhibited a similar proportionality of response as demonstrated using the comparator sample. 16/190 was commutable in some but not all methods. On the basis of these results, it was agreed by the WHO Expert Committee on Biological Standardization to establish 16/190 as a WHO Reference Reagent for AMH with a content defined by consensus immunoassay of 489 ng/ampoule.

Evaluation of cerebrovascular reactivity by ultrasonography in type 2 diabetic patients with hypertension*

BACKGROUNDCerebrovascular reactivity (CVR) reflects cerebrovascular reserve capacity, and cerebrovascular reactivity damage prognosticates a very high risk of stroke. OBJECTIVETo evaluate CVR by detecting the increase rate of blood flow volume of middle cerebral artery (MCA) before and after breathholding in diabetic patients with hypertension, and observe the effects of hypertension on cerebrovascular reserve capacity of diabetic patients. DESIGNControlled observation. SETTINGSDepartment of Function, Affiliated Hospital of Hebei University; Department of Special Diagnosis, the 202 Hospital of Chinese PLA. PARTICIPANTSInpatients or outpatients with type 2 diabetes mellitus (DM) or primary hypertension admitted to Departments of Gastroenterology and Cardiology, Affiliated Hospital of Hebei University and the 202 Hospital of Chinese PLA from April to December 2004 were involved in this experiment. Inclusive criteria: type 2 DM met the criteria of the report on diabetes diagnosis announced in 1999 by WHO expert committee, totally 88 patients were involved. Primary hypertension met the diagnosis criteria announced in 1999 by WHO/ISH, totally 42 patients were involved. Another group of 43 concurrent subjects who received physical examination served as controls. According to the disease condition, the involved patients were assigned into 3 groups: DM group (only diabetic patients), hypertension group (only hypertension patients) and DM complicated with hypertension group (diabetic patients with hypertension). Informed consent for the examination was obtained from all the involved subjects. METHODSBefore MCA of subjects was detected, bilateral carotid artery was routinely detected by high-frequency ultrasonography. Subjects were rejected when stenosis rate of unilateral internal carotid artery or common carotid artery ≥ 70%. Vessels were expanded with transcranial color Duplex Doppler by breath holding test for detecting vascular reactivity. Hypercapnia was created by BHT. The mean velocity and diameter of blood flow were detected under the quiescent condition and 25 s after breath holding with transcranial color-coded duplex sonography. The volume of blood flow of MCA was calculated according to the following formula: Volume of blood flow of MCA (mL/ min) = (the diameter of blood flow /2)2 × π × mean blood flow velocity × 60. The increase rates of mean blood flow velocity and blood flow volume of patients with hypercapnia were calculated as compared with under the quiescent condition to evaluate cerebrovascular reactivity. MAIN OUTCOME MEASURESMean blood flow velocity, blood flow diameter and MCA blood flow volume as well as the increase rates of them. RESULTSAmong the 173 participates, 103 patients and 39 healthy controls were involved in the final analysis, and the other 31 dropped out due to not accomplishing the examination, (1)Comparison of blood flow parameter of MCA under the quiescent condition: The mean blood flow velocity of DM complicated by hypertension group was significantly higher than that of DM group (P < 0.05) and control group (P < 0.05); The blood flow diameter of DM complicated by hypertension group was significantly smaller than that of control group (P < 0.01). Under the quiescent condition, significant difference was not found in the intergroup comparison of blood flow volume of MCA. (2) Comparison of increase rate of blood flow parameter: In the DM group, hypertension group. DM complicated by hypertension group and control group, the increase rate of mean blood flow velocity of was (29.34±4.50) %, (29.35±4.35) %, (26.68±4.99) % and (30.99±3.54) %, respectively, the increase rate of blood flow volume of MCA was (35.32±5.08) %, (35.36±6.16) %, (31.78±7.11) % and (37.26±4.17) %, respectively, and the increase rate of blood flow diameter was (2.29±1.09) %, (2.27±0.95) %, (1.97±1.05) % and (2.36±0.46) %, respectively. The increase rate of mean blood flow velocity and that of blood flow volume of MCA in the DM complicated by hypertension group were significantly lower than those in the other 3 groups (P < 0.05). CONCLUSIONCVR is markedly lowered and cerebrovascular reserve capacity is damaged in diabetic patients with hypertension.

Identification of Nonylphenol and Glucolipid MetabolismRelated Proteins in the Serum of Type 2 Diabetes Patients

To identify serum nonylphenol (NP) and glucolipid metabolism-related proteins in Type 2 diabetes (T2D) patients. We performed a hospital-based, case-control study in patients admitted to the Department of Endocrinology, Hospital of Zunyi Medical University, Zunyi City, China from Mar to Nov of 2014. The study included 112 T2D cases diagnosed in accordance with the 2013 WHO Expert Committee Diabetes Diagnosing Criteria, and 125 healthy individuals with normal fasting blood glucose (FBG) when receiving physical examination in the same period in the Municipal Physical Examination Center. Blood samples from subjects in the 2 groups underwent detection of biochemical indices, including FBG, blood fat, and NP. Glucolipid metabolism-related proteins, including estrogen receptor (ER), sterol regulatory element-binding protein-1c (SREBP-1c), wingless-type MMTV integration site family member 5a (Wnt5a), and peroxisome proliferator-activated receptor-γ (PPAR-γ). These indices were compared between the 2 groups to analyze the correlation between serum NP levels and glucolipid metabolic proteins. The subjects in the diabetes group had higher triglycerides (TG), total cholesterol (TC), NP, ER, SREBP-1c, Wnt5a, FBG, and TG levels than the healthy group, but lower levels of low-density lipoprotein cholesterol (LDL-C) and PPAR-γ than the healthy group. No significant differences in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were found between the two groups. The serum NP levels were shown to be positively correlated with SREBP-1c but negatively correlated with PPAR-γ. The serum NP levels of T2D patients is higher than the levels in healthy controls, and its levels correlate with SREBP-1c and PPAR-γ levels.

Removal of the innocuity test from The International Pharmacopoeia and WHO recommendations for vaccines and biological products

The innocuity test was indicated as a quality control test to release pharmaceutical and biological products to the market. The test was intended to detect possible extraneous toxic contaminants derived from the manufacturing processes of the product. The test was included in WHO Recommendations and Guidelines for vaccines, biotherapeutics and blood products and in some monographs on antibiotics in The International Pharmacopoeia. Over the past years, the requirements in WHO Recommendations/Guidelines for conducting the test evolved such that it could be waived for routine release of product once consistency of production was established to the satisfaction of the NRA, or that the need for this test should be discussed and agreed with the NRA. However, some users of WHO written standards for biologicals (i.e., Recommendations, Guidelines) and WHO specifications for pharmaceuticals (i.e., The International Pharmacopoeia) requested that the innocuity test be deleted from WHO written standards based on its lack of specificity and scientific relevance. In response to that request, we studied the history of this test and its use by the member states of WHO, and the recommendations in WHO written standards. The outcomes of the study were reviewed by the relevant WHO Expert Committee on Biological Standardization and Expert Committee on Specifications for Pharmaceutical Products who then decided to discontinue this test in WHO Recommendations for vaccines and biologicals and to omit the test from The International Pharmacopoeia.