International Patent Survey of Products and Processes Concerning Homeopathy.

BACKGROUND: Homeopathy is a complementary medicine characterized by the use of diluted and potentized medicines. Innovations in this area are constantly being proposed in the relevant literature, such as scientific articles and patents. The objective of this study was to carry out a patent survey of homeopathic products and processes. METHODS: A free and international patent database, Espacenet, was used. The search was carried out using the keyword homeop*, with two approaches: (1) no date restrictions for the search and (2) a date limit for the publication years 2008 to 2018. The patents from the limited period were organized as depositor countries, ownerships and groups, including homeopathic formulations, equipment, packaging, production procedures, and analytical methods. RESULTS: Without date restriction, 601 patents were identified in the survey. Of these, 174 were related to homeopathy and published in the period 2008 to 2018. Technologies come mainly from the following countries: United States (55 patents), Russia (24), Germany (15), France (13), India (12), Ukraine (11), Brazil (6), and China (6). Among the ownerships, 69% of patent applications were by independent depositors, 23% by companies, 7.5% by universities, and 0.5% by company/university partnerships. New formulations represented 75.9% of technologies, whilst the others comprised 14.3% for equipment, 3.8% for drugs packaging, 3.8% for production procedures, and 2.2% for analytical methods. CONCLUSIONS: The present review helps visualize the homeopathy-related patents published in recent years, as well as the main countries and researchers investing in the field of homeopathy.

Homeopathy Assessment-Contribution of the Human Sciences.

The recent questions about homeopathy raised by some sceptics have focused an awareness on this therapy and led different protagonists among the scientific community to seek a much-needed re-assessment. The inputs coming from external but benevolent experts will broaden the knowledge and the consciousness of the whole medical community, and more widely of the public, about the meaning and the value of homeopathy.Looking at this from the point of view of the human sciences gives a perspective on the universality of the philosophy that underlies homeopathic thinking, which is particularly visible in the methodological similarities between homeopathic provings and sociological or anthropological observations. It also explains how this view of health and care coincides with the expectations of the public, who no longer want a limited mechanical approach to the human body or more generally to the environment.The input to homeopathy of the human sciences, with their methodological tools and approaches, and highlighting the possibilities offered by mixed-methods research, could enable these notions to be heard and shared in the wider scientific community.

"Imagine the Perfect Vaccine": Homeopathic Vaccine Alternatives and Vaccine Discourse in English Canada.

Advocates of homeopathic vaccines, also known as nosodes, reimagined the risks and benefits of vaccination from 1999 to 2015 by comparing "risky" vaccines to "risk-free" nosodes. I argue that nosodes allowed for a complementary argument to anti-vaccine discourse, fundamentally altering what had been framed as a choice between the risks of vaccination and the risks of vaccine-preventable disease. Despite evidence of their efficacy being flawed, advocates presented nosodes as an alternative to vaccines and a middle ground between anti-vaccination and vaccination. While a campaign from 2013 to 2015 tried to expose nosodes as ineffective, I argue that the campaign was unsuccessful. Instead, the mainstream media brought more attention to nosodes. The history of nosodes further complicates the history of vaccines and alternative medicine in Canada by adding vaccine alternatives to the growing literature on vaccine hesitancy.

Is opium use associated with an increased risk of lung cancer? A case-control study.

BACKGROUND: In recent years, lung cancer (LC) incidence has increased in Iran. The use of opium and its derivatives (O&D) has increased as well. This study aimed to investigate the association between the use of O&D and LC incidence. METHODS: In this case-control study conducted in Kerman, Iran; 140 patients with lung cancer and 280 healthy controls matched by age, sex, and place of residence were included. Data, including O&D use, cigarette smoking, alcohol use, and diet, were collected using a structured questionnaire. The relation between the use of O&D and LC was evaluated using conditional logistic regression adjusted for tobacco smoking, education, daily intake of fruit, vegetables, red meat, and hydrogenated fats. RESULTS: Opium ever-use was associated with an increased risk of LC (Adjusted Odds Ratio (AOR) =5.95, 95% CI: 1.87-18.92). Participants were divided into low and high use groups based on the median of opium use in the control group. A significant dose-response relation was observed between the amount of daily O&D use and LC; and the relation was stronger in high users (AOR low users = 3.81% CI: 1.13-12.77 and OR high users = 9.36, 95% CI: 2.05-42.72). Also, LC was higher among participants starting the use of O&D at younger ages (≤ 41 years old vs never users AOR = 8.64, 95% CI: 1.90-39.18) compared to those who started at an older age (> 41 years old vs never users, AOR = 4.71, 95% CI: 1.38-16.08). The association between opium, and lung cancer among non-smokers was OR: 6.50 (95% CI: 2.89 to 14.64). CONCLUSION: The results of this study show that opium use is probably a dose related risk factor for lung cancer.

Homeopathic Remedies in Psychiatric Disorders: A Meta-analysis of Randomized Controlled Trials.

PURPOSE/BACKGROUND: Homeopathy is a complementary and alternative medicine. Conclusive evidence on the plausibility, efficacy, and safety of these treatments is not currently available. Nonetheless, homeopathic remedies (HRs) are widespread throughout the world and especially in mental disorders. The aim is to assess the efficacy of HRs in the treatment of mental disorders. METHODS/PROCEDURES: We performed a Medline/Embase search for studies written in English and published from any date to October 23, 2018. All randomized controlled trials enrolling patients with any psychiatric disorder and comparing HR with placebo, no treatment, or other psychotropic drugs were included. FINDINGS/RESULTS: A total of 212 studies were screened, 9 met all selection criteria and reported data on major depressive disorder (MDD) (n = 4), generalized anxiety disorder (n = 1), attention-deficit/hyperactivity disorder (n = 2), and premenstrual syndrome/dysphoric disorder (n = 2). Eight of 9 randomized controlled trials showed high risk of bias. Homeopathy showed greater efficacy in MDD compared with fluoxetine, and in premenstrual syndrome/dysphoric disorder compared with placebo, whereas no difference emerged between homeopathy and placebo in MDD and attention deficit/hyperactivity disorder. IMPLICATIONS/CONCLUSIONS: Available data on homeopathy in psychiatric disorders are insufficient to support their use in clinical practice.

Natural language processing of Reddit data to evaluate dermatology patient experiences and therapeutics.

BACKGROUND: There is a lack of research studying patient-generated data on Reddit, one of the world's most popular forums with active users interested in dermatology. Techniques within natural language processing, a field of artificial intelligence, can analyze large amounts of text information and extract insights. OBJECTIVE: To apply natural language processing to Reddit comments about dermatology topics to assess for feasibility and potential for insights and engagement. METHODS: A software pipeline preprocessed Reddit comments from 2005 to 2017 from 7 popular dermatology-related subforums on Reddit, applied latent Dirichlet allocation, and used spectral clustering to establish cohesive themes and the frequency of word representation and grouped terms within these topics. RESULTS: We created a corpus of 176,000 comments and identified trends in patient engagement in spaces such as eczema and acne, among others, with a focus on homeopathic treatments and isotretinoin. LIMITATIONS: Latent Dirichlet allocation is an unsupervised model, meaning there is no ground truth to which the model output can be compared. However, because these forums are anonymous, there seems little incentive for patients to be dishonest. CONCLUSIONS: Reddit data has viability and utility for dermatologic research and engagement with the public, especially for common dermatology topics such as tanning, acne, and psoriasis.

Off-label prescribing during pregnancy in France: the NéHaVi cohort
.

OBJECTIVE: To describe the off-label medication use in a cohort of pregnant women. MATERIAL AND METHODS: We performed a multicenter prospective longitudinal observational study in the Haute-Vienne department (France) called the NéHaVi cohort ("Né en Haute-Vienne" meaning "born in Haute-Vienne"). Women who had given birth to a viable baby in one of three maternity wards in the Haute-Vienne were included in the study after giving their informed consent. Data on the progress and outcome of pregnancies, childbirth, and drug or toxic exposure during pregnancy were collected. Drugs were classified, according to the labeling of the summary of product characteristics (SmPC) regarding the use in pregnancy, as follows: on-label, off-label at risk, and off-label contra-indicated. RESULTS: During their pregnancy, the 397 included women gave birth to 400 viable babies (209 boys, 191 girls, 3 sets of twins). All women had used at least 1 health product: 3,533 (92%) drugs, 298 (7.5%) homeopathic products, and 18 (0.5%) herb derivatives. The mean number of different drugs taken was 8.9 ± 5.3 (min 1, max 31). All pregnant women used at least 1 drug either with a license or considered as safe to take during pregnancy. Among the 2,538 (71.6%) on-label drugs, the most frequently used were analgesics (n = 611, 24.1%) (acetaminophen (n = 566)), antianemia preparations (n = 528, 20.8%), drugs for functional gastrointestinal disorder (n = 269, 10.6%), vitamins (n = 192, 7.5%), drugs for acid-related disorders (n = 148, 5.8%), and antibacterials (n = 118, 4.6%). In total, 321 (80.9%, 95% CI: 77.0 - 84.7) pregnant women used at least 1 off-label drug; and more precisely, 285 (71.8%, 95% CI: 67.4 - 76.2) used at least 1 off-label high-risk drug, and 189 (47.6%, 95% CI: 42.7 - 52.5) at least 1 contra-indicated drug. Among the 995 off-label drugs (28.2%), 760 (21.5%) were considered high-risk, including vasoprotectives (n = 156, 20.5%) (treatment of hemorrhoids (n = 147)), antithrombotic agents (n = 91, 11.6%) (heparins (n = 88)), and calcium channel blockers (n = 88, 11.6%). Lastly, 235 (6.7%) off-label drugs used were contraindicated medications (non-steroidal anti-inflammatory drugs during the 3rd trimester (n = 231)). Five babies were born with malformations not related to the drugs used during pregnancy. CONCLUSION: We showed for the first time the magnitude of off-label prescription during pregnancy in France. Women and health professionals should be made more aware of the potential drug-induced risk during pregnancy. Drug adverse effects during pregnancy should be evaluated through an improved notification in pharmacovigilance and appropriate pharmacoepidemiologic studies in order to change SmPC labelings as early as possible, when necessary.

The usage of over-the-counter products by private insured patients in Germany - a claims data analysis with focus on complementary medicine.

BACKGROUND: An important contribution to well-being of human beings can be observed by the use of self-medication products that is reflected in the constantly growing volume of over-the-counter (OTC) drugs. The aim of the current study was to extend the measurement concept for OTCs by exploring the relevance of the peripheral assortment provided by the widely accepted framework of the Anatomical Therapeutical and Chemical (ATC) classification of the WHO. METHODS: The focus was on the prescriptions and drug-related receipts submitted by privately insured persons to 18 private health insurers (PHIs) in Germany from the year 2016. The age- and gender-specific average claims amount per risks of outpatient drug expenditure were used as weights to scale up the relative distributions of the item amounts. The ATC-classification defines the commodity groups and discriminates between the main and the peripheral assortment. A descriptive analysis assessed the OTC frequencies and sum scores of the product groups within the main and peripheral assortment whereby the study group explored and assessed the relevance of each category independently according to the OTCs and integrative medicines. RESULTS: The analysis included 22.1 Mio. packages from the main assortment and examined 10.1 Mio. packages from the peripheral assortment. The latter was examined thoroughly and the commodity groups "Pharmaceutical food products", "Medicinal products for special therapy options" and particular "Hygiene and body care products" meet the defined requirements for OTCs relevant for integrative medicines. A high proportion of OTC products from the peripheral assortment was associated with the categories "medicinal products for special therapy options". Homeopathy and anthroposophy present two special therapy options, which are relevant for the extended OTC measurement. CONCLUSIONS: The analysis of OTC drugs is feasible when the main and the peripheral assortment is available and enable to integrate about 18% of all OTCs, which are neglected by the common ATC-based approach. The presented extended approach may help to identify potential users of OTCs or people in need of OTC use. In case of the highly disputed homeopathy and anthroposophy products, more research among interactions with prescriptions drugs (Rx), nutrition's and other potentially harmful exposures is recommended.

Will We Miss the Opportunity Again?

Coronavirus disease 2019 (COVID-19), caused by a new coronavirus, first appeared in late 2019. What initially seemed to be a mild influenza quickly revealed itself as a serious and highly contagious disease, and the planet was soon faced with a significant morbidity and mortality associated with this pathogen. For homeopathy, shunned during its 200 years of existence by conventional medicine, this outbreak is a key opportunity to show potentially the contribution it can make in treating COVID-19 patients. This should be done through performance of impeccably controlled, prospective, randomized clinical trials, with publication of their findings in well-ranked conventional medicine journals. If the homeopathy community fails to take advantage of this rare opportunity, it might wait another century for the next major pandemic.

Use of complementary and alternative medicine treatments by mothers of children with developmental disabilities: a cross sectional study.

This study aims to determine the rates of complementary and alternative medicine methods used by mothers of children with developmental disabilities, reasons for using methods, and comparison of methods according to diagnosis groups. The cohort in this cross-sectional and correlational study consisted of the mothers of 390 students with developmental disabilities; 77.2% of the mothers reported using at least one complementary and alternative medicine treatment. The highest level of use was found in the groups of mothers of children with cerebral palsy (100%) and autism spectrum disorder (88.5%). The most commonly used treatments were biological therapies consisting of special diets and multivitamins, manipulative and body-based methods including massage and exercise, and mind-body interventions such as prayer, wearing amulets, and seeking help from a Muslim preacher (hodja). However, mothers never used alternative medicine treatments such as homeopathy, acupuncture, or Ayurveda, nor did they use energy-based healing techniques such as reiki, tai chi, yoga, kinesiology, or neurofeedback exercises. Health care professionals, especially nurses as health care team members, should be knowledgeable and careful about the benefits, side effects, administration methods, and contraindications of complementary and alternative medicine treatments.

Do sociodemographic characteristics associated with the use of CAM differ by chronic disease?

BACKGROUND: Complementary and alternative medicine (CAM) is oftenused to alleviate the discomfort, disability and pain involved in many chronic diseases. Besides this, females, middle-aged and higher educated people are also known to use CAM the most. This study explores whether the sociodemographic characteristics associated with CAM use differ by type of disease. METHODS: The following data were taken from the Belgian Health Interview Survey 2013 for the individuals aged 15+ years (n = 8942): sociodemographic characteristics, past 12-month diseases (using a list) and contact with a homeopath, chiropractor, acupuncturist and/or osteopath (CAM-therapists) in the past year. The association between CAM use and disease, controlled for gender, age, education and conventional medicine use, was assessed through logistic regressions. When interactions with the sociodemographic characteristics were found, stratified regressions were conducted. RESULTS: People with musculoskeletal diseases [odds ratio (OR) = 2.6], allergy (OR = 1.4) and severe headache (OR = 1.5) had higher odds of using CAM in the past year with statistical significance. For musculoskeletal diseases, the odds of using CAM was higher, with statistical significance, for every sociodemographic subclass. For allergy, CAM use was higher among men, people aged 45+ years and lower educated people, while for severe headache CAM use was higher among women, people aged 45+ years and higher educated people, all with statistical significance. CONCLUSIONS: Sociodemographic characteristics associated with CAM use differ by diseases. The role of CAM in disease management cannot be ignored. Making physicians aware for which disease CAM is used and by whom, may facilitate disease management.

A cross-sectional assessment of knowledge, attitudes and self-perceived effectiveness of complementary and alternative medicine among pharmacy and non-pharmacy university students.

BACKGROUND: Traditional medicine has always been Pakistan's cultural heritage, providing health care to a large part of its population. Thus, we aimed to assess and compare the knowledge, attitude, and perception about complementary and alternative medicine (CAM) between pharmacy and non-pharmacy students, the results of which may be helpful in devising national health-education policy. METHODS: A cross-sectional study was conducted by enrolling 937 students, pharmacy (437) and non-pharmacy (500), of Punjab University, Lahore. A self-administered questionnaire was used for data collection. Data were analyzed using SPSS. (IBM v22). RESULTS: Data suggested that majority of students knew about the use of traditional herbs and considered massage (P: 84.4%, NP: 82%, p = 0.099), homeopathy, herbs (P: 86.5%, NP: 81%, p = 0.064], yoga [P: 357 (81.7%), NP: 84%), p = 0.42] and spiritual healing (P: 85.6%, NP: 86.2%, p = 0.55) as effective and least harmful CAM modalities. The pharmacy students had better knowledge about CAM modalities compared to non-pharmacy students. Despite utilizing non-reliable sources of CAM information and their belief that CAM is practiced by quacks, the majority of students had positive attitudes and perceptions about CAM usage. Students also believed that CAM had a positive impact on health outcomes [P: 3.19 ± 1.04, NP: 3.02 ± 1.09, p = 0.008] and acceded to include CAM in the pharmacy curriculum. However, non-pharmacy students scored higher in their beliefs that CAM usage should be discouraged due to the non-scientific basis of CAM (P: 3.04 ± 0.97, NP: 3.17 ± 1.02, p = 0.028) and a possible threat to public health (P: 3.81 ± 1.74, NP: 4.06 ± 1.56, p = 0.02). On the other hand, pharmacy students believed that patients might get benefits from CAM modalities (P: 4.31 ± 1.48, NP: 4.12 ± 1.45, p = 0.02). Majority of students perceived that spiritual healing is the most useful and safer CAM modality, while acupuncture (P: 25.4%, NP: 21.8%, p = 0.0005), hypnosis (P: 26.8%, NP: 19.6%, p = 0.001) and chiropractic (P: 18.8%, NP: 11.6%, p = 0.0005) were among the harmful ones. CONCLUSION: In conclusion, despite poor knowledge about CAM, students demonstrated positive attitudes and beliefs regarding CAM. They exhibited better awareness about yoga, spiritual healing/prayer, herbs, and massage. Students also showed willingness to advance their knowledge about CAM and favored its inclusion in the curriculum.

A Study of Siberia's Medicinal Plants Used in Homeopathy.

BACKGROUND: A current priority of national health care in Russia is to expand the range of drug substances, based on naturally occurring compounds, to use for treating socially significant diseases, such as cancer and cardiovascular diseases. OBJECTIVE: The main objective of our study was to compile a contemporary list of Siberia's 'homeopathic plants', describing for each plant the corresponding therapeutic indications or main symptoms of disease. METHODS: The textbook, Global Resources of Homeopathic Medicinal Raw Materials, was used to scrutinize the 709 species that are allowed for use in Russia, designating each of the 709 as either indigenous or non-indigenous to the region of Siberia. A homeopathic repertory, containing description of more than 1,800 single-component homeopathic medicines, was used to identify Siberia's medicinal plants used in homeopathy, along with the medical indications of each. RESULTS: The medicinal plants of Siberia used in homeopathy comprise 137 species of flowering plants, gymnosperms and sporophytes, belonging to 52 families. The most represented are the Compositae, Rosaceae, and Lamiaceae families. CONCLUSION: The inventory of Siberian plants has allowed us to identify the plants of this region used in homeopathy and will help to inform research on additional species with the potential for introduction into homeopathic practice.

An Assessment of a Public Health Initiative of Homeopathy for Primary Teething.

BACKGROUND: During primary teething, children suffer from running nose, mild fever, diarrhoea and other mild irritations and inflammations. A public health programme, 'Homoeopathy for the Healthy Child', was undertaken on a pilot basis focusing on promotion of healthy teething by provision of home-based care through six pre-identified homeopathic medicines for complaints commonly observed during primary teething. This article assesses the feasibility of this programme and reports the impact of this initiative on teething profile in children and episodes of diarrhoea and upper respiratory tract infection (URTI). MATERIALS AND METHODS: Accredited Social Health Activists (ASHAs) were trained in child care and usage of a kit comprising six medicines, namely Calcarea phosphoricum 6X (CP), Ferrum phosphoricum 3X, Magnesium phosphoricum 6X, Belladonna 30C, Chamomilla 30C and Podophyllum 30C. Calcarea phosphoricum was given regularly to each participating child from 6 months to 1 year of age. Home-based care for diarrhoea, URTI and mild fever was provided by ASHAs using the other five medicines in the kit. Dentition pattern and diarrhoea/URTI episodes were recorded over a period of the next 12 months. RESULTS: Eleven thousand four-hundred and twenty-six children were followed up regularly. Amongst those who enrolled at 6-7 months, a larger proportion of children were approaching expected teething in successive months as compared with children enrolled at 12 months, thus indicating that teething delays, if any, were overcome during this period. Incidence of diarrhoea and URTI showed decrease in the months after enrolment. Children responded favourably to the medicines given by ASHAs at the time of diarrhoea/URTI episodes, and ASHAs expressed satisfaction with the programme. CONCLUSION: An approach with regular use of CP and home-based care with homeopathy through health workers for common problems in teething children is acceptable to the community and enhances outreach of services to the public at large. Observations in terms of the healthy teething period may be further validated through studies of homeopathy with suitable comparator group.

Effects of Ultra-Low-Dose Aspirin in Thrombosis and Haemorrhage.

BACKGROUND: Aspirin is the oldest and possibly the most widely used pharmacologically active substance still used in allopathic medicine. Its effect on fever and inflammation has paved the way to its anti-thrombotic effect. Dilutions of aspirin have been tested for many years in the University of Bordeaux, in humans as well as in animal models. METHODS: This article is a review of the totality of articles published by the Laboratory of Hematology of the Faculty of Pharmacy of the University of Bordeaux, reporting different doses and dilutions of aspirin, different kinds of inhibitors, transgenic mice and animal models of disease such as portal hypertension and cirrhosis. RESULTS: Homeopathic dilutions of aspirin, notably 15 cH, have shown a pro-thrombotic effect in humans and in in-vivo animal studies. Longitudinal studies in rats have also shown an initial anti-thrombotic effect followed by a pro-thrombotic effect of aspirin several days after a single high-dose administration. This pro-thrombotic effect seems to act by inhibiting the cyclooxygenase (COX)-2 pathway in studies performed with COX selective inhibitors and in knock-out mice without COX-1 or COX-2. This effect may explain the thrombo-embolic complications described after aspirin withdrawal for the purposes of surgery or after non-compliance with anti-platelet therapy, and it may be beneficial in normalising primary haemostasis and decreasing haemorrhage in animal models of portal hypertension and cirrhosis. CONCLUSIONS: Aspirin 15 cH acts through the inhibition of the COX-2 pathway producing a clear pro-thrombotic effect. Further studies should clarify if the pro-thrombotic effect of aspirin withdrawal and the effect of aspirin 15 cH are related, as secondary effects of the same drug. Clarifying this last outcome may be of great significance to public health.

Effect of Adjuvant Homeopathy with Usual Care in Management of Thrombocytopenia Due to Dengue: A Comparative Cohort Study.

BACKGROUND: Dengue is an emerging threat to public health. At present, no clear modalities are available for the prevention and management of thrombocytopenia due to dengue. This article reports the clinical outcomes of integrative homeopathic care in a hospital setting during a severe outbreak of dengue in New Delhi, India, during the period September to December 2015. METHODS: Based on preference, 138 patients received a homeopathic medicine along with usual care (H+UC), and 145 patients received usual care (UC) alone. Assessment of thrombocytopenia (platelet count < 100,000/mm3) was the main outcome measure. Kaplan-Meier analysis enabled comparison of the time taken to reach a platelet count of 100,000/mm3. RESULTS: There was a statistically significantly greater rise in platelet count on day 1 of follow-up in the H+UC group compared with UC alone (mean difference = 12,337; 95% confidence interval [CI], 5,421 to 19,252; p = 0.001). This trend persisted until day 5 (mean difference = 14,809; 95% CI, 1,615 to 28,004; p = 0.02). The time taken to reach a platelet count of 100,000/mm3 was nearly 2 days earlier in the H+UC group compared with UC alone (H+UC: 3.44 days ± standard error of the mean [SEM] 0.18; 95% CI, 3.08 to 3.80; UC: 5.28 days ± SEM 0.29; 95% CI, 4.71 to 5.86; p < 0.001). CONCLUSION: These results suggest a positive role of adjuvant homeopathy in thrombocytopenia due to dengue. Randomized controlled trials may be conducted to obtain more insight into the comparative effectiveness of this integrative approach.

[Sociodemographic profile of the homeopathy user in Spain]. / Perfil sociodemográfico del usuario de la homeopatía en España.

OBJECTIVE: To identify the sociodemographic profile of the homeopathy user in Spain. DESIGN: Quantitative study. LOCATION: Spain. CORPUS: The Centre for Sociological Research database (Study 3205, February 2018), with a total of 2,486 interviews, and the sub-sample that includes all patients who have claimed to use homeopathy in Spain in the last 12 months (n=124). MAIN MEASUREMENTS: The percentages, means and/or standard deviation of the factors were calculated, as well as the significance of the changes in the different variables analysed in the general population, and the specific users of homeopathy in Spain. This was determined by the variance analysis or Pearson's χ2 test, depending on the nature of the variable in the study. RESULTS: The homeopathy user-type profile in Spain is a woman, of middle/high social status, with higher university studies, and with a progressive political ideology. CONCLUSIONS: The Spanish profile is similar to that in other international studies.

Preimplantation genetic testing for aneuploidy by microarray analysis of polar bodies in advanced maternal age: a randomized clinical trial.

STUDY QUESTION: Does preimplantation genetic testing for aneuploidy (PGT-A) by comprehensive chromosome screening (CCS) of the first and second polar body to select embryos for transfer increase the likelihood of a live birth within 1 year in advanced maternal age women aged 36-40 years planning an ICSI cycle, compared to ICSI without chromosome analysis? SUMMARY ANSWER: PGT-A by CCS in the first and second polar body to select euploid embryos for transfer does not substantially increase the live birth rate in women aged 36-40 years. WHAT IS KNOWN ALREADY: PGT-A has been used widely to select embryos for transfer in ICSI treatment, with the aim of improving treatment effectiveness. Whether PGT-A improves ICSI outcomes and is beneficial to the patients has remained controversial. STUDY DESIGN, SIZE, DURATION: This is a multinational, multicentre, pragmatic, randomized clinical trial with intention-to-treat analysis. Of 396 women enroled between June 2012 and December 2016, 205 were allocated to CCS of the first and second polar body (study group) as part of their ICSI treatment cycle and 191 were allocated to ICSI treatment without chromosome screening (control group). Block randomization was performed stratified for centre and age group. Participants and clinicians were blinded at the time of enrolment until the day after intervention. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertile couples in which the female partner was 36-40 years old and who were scheduled to undergo ICSI treatment were eligible. In those assigned to PGT-A, array comparative genomic hybridization (aCGH) analysis of the first and second polar bodies of the fertilized oocytes was performed using the 24sure array of Illumina. If in the first treatment cycle all oocytes were aneuploid, a second treatment with PB array CGH was offered. Participants in the control arm were planned for ICSI without PGT-A. Main exclusion criteria were three or more previous unsuccessful IVF or ICSI cycles, three or more clinical miscarriages, poor response or low ovarian reserve. The primary outcome was the cumulative live birth rate after fresh or frozen embryo transfer recorded over 1 year after the start of the intervention. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 205 participants in the chromosome screening group, 50 (24%) had a live birth with intervention within 1 year, compared to 45 of the 191 in the group without intervention (24%), a difference of 0.83% (95% CI: -7.60 to 9.18%). There were significantly fewer participants in the chromosome screening group with a transfer (relative risk (RR) = 0.81; 95% CI: 0.74-0.89) and fewer with a miscarriage (RR = 0.48; 95% CI: 0.26-0.90). LIMITATIONS, REASONS FOR CAUTION: The targeted sample size was not reached because of suboptimal recruitment; however, the included sample allowed a 90% power to detect the targeted increase. Cumulative outcome data were limited to 1 year. Only 11 patients out of 32 with exclusively aneuploid results underwent a second treatment cycle in the chromosome screening group. WIDER IMPLICATIONS OF THE FINDINGS: The observation that the similarity in birth rates was achieved with fewer transfers, less cryopreservation and fewer miscarriages points to a clinical benefit of PGT-A, and this form of embryo selection may, therefore, be considered to minimize the number of interventions while producing comparable outcomes. Whether these benefits outweigh drawbacks such as the cost for the patient, the higher workload for the IVF lab and the potential effect on the children born after prolonged culture and/or cryopreservation remains to be shown. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the European Society of Human Reproduction and Embryology. Illumina provided microarrays and other consumables necessary for aCGH testing of polar bodies. M.B.'s institution (UZBrussel) has received educational grants from IBSA, Ferring, Organon, Schering-Plough, Merck and Merck Belgium. M.B. has received consultancy and speakers' fees from Organon, Serono Symposia and Merck. G.G. has received personal fees and non-financial support from MSD, Ferring, Merck-Serono, Finox, TEVA, IBSA, Glycotope, Abbott and Gedeon-Richter as well as personal fees from VitroLife, NMC Healthcare, ReprodWissen, BioSilu and ZIVA. W.V., C.S., P.M.B., V.G., G.A., M.D., T.E.G., L.G., G.Ka., G.Ko., J.L., M.C.M., M.P., A.S., M.T., K.V., J.G. and K.S. declare no conflict of interest. TRIAL REGISTRATION NUMBER: NCT01532284. TRIAL REGISTRATION DATE: 7 February 2012. DATE OF FIRST PATIENT'S ENROLMENT: 25 June 2012.

Lead poisoning outbreak among opium users in the Islamic Republic of Iran, 2016-2017.

OBJECTIVE: To describe an outbreak of lead poisoning among opium users in the Islamic Republic of Iran and estimate the number of affected people in the country. METHODS: We used data from the country's largest poison treatment centre to illustrate the epidemiology of an outbreak of lead poisoning in oral opium users. We describe the government's referral and treatment guidelines in response to the outbreak. Based on the number of individuals treated and previous studies on the prevalence of oral opium use we estimated the total number of people at risk of lead-contaminated opium nationwide. FINDINGS: In February 2016, we noticed a steep increase in the numbers of oral opium users referred to our poison treatment centre with abdominal pain, anaemia and constipation. Numbers peaked in June 2016 but the outbreak was ongoing in August 2017. The mean blood lead level in a sample of 80 patients was 140.3 µg/dL (standard deviation: 122.6). Analysis of an illegal opium sample showed 3.55 mg lead in 1 g opium. Treatment was exposure reduction with opioid substitutes and laxatives, or chelation therapy if indicated. Over 7 months, 4294 poison cases were seen at main referral hospitals in Tehran out of an estimated 31 914 oral opium users in the city. We estimate more than 260 000 out of 773 800 users nationwide remain untreated and at risk of poisoning. CONCLUSION: Lead-contaminated opium and heroin that has transited through the Iranian markets is a global risk and highlights a need for better monitoring of illegal drug supplies.

Comparison of the TOFscan and the TOF-Watch SX during Recovery of Neuromuscular Function.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Quantitative neuromuscular monitoring is required to ensure neuromuscular function has recovered completely at the time of tracheal extubation. The TOFscan (Drager Technologies, Canada) is a new three-dimensional acceleromyography device that measures movement of the thumb in multiple planes. The aim of this observational investigation was to assess the agreement between nonnormalized and normalized train-of-four values obtained with the TOF-Watch SX (Organon, Ireland) and those obtained with the TOFscan during recovery from neuromuscular blockade. METHODS: Twenty-five patients were administered rocuronium, and spontaneous recovery of neuromuscular blockade was allowed to occur. The TOFscan and TOF-Watch SX devices were applied to opposite arms. A preload was applied to the TOF-Watch SX, and calibration was performed before rocuronium administration. Both devices were activated, and train-of-four values were obtained every 15 s. Modified Bland-Altman analyses were conducted to compare train-of-four ratios measured with the TOFscan to those measured with the TOF-Watch SX (when train-of-four thresholds of 0.2 to 1.0 were achieved). RESULTS: Bias and 95% limits of agreement between the TOF-Watch SX and the TOFscan at nonnormalized train-of-four ratios between 0.2 and 1.0 were 0.021 and -0.100 to 0.141, respectively. When train-of-four measures with the TOF-Watch SX were normalized, bias and 95% limits of agreement between the TOF-Watch SX and the TOFscan at ratios between 0.2 and 1.0 were 0.015 and -0.097 to 0.126, respectively. CONCLUSIONS: Good agreement between the TOF-Watch SX with calibration and preload application and the uncalibrated TOFscan was observed throughout all stages of neuromuscular recovery.