ESHRE guideline: number of embryos to transfer during IVF/ICSI†.

STUDY QUESTION: Which clinical and embryological factors should be considered to apply double embryo transfer (DET) instead of elective single embryo transfer (eSET)? SUMMARY ANSWER: No clinical or embryological factor per se justifies a recommendation of DET instead of eSET in IVF/ICSI. WHAT IS KNOWN ALREADY: DET is correlated with a higher rate of multiple pregnancy, leading to a subsequent increase in complications for both mother and babies. These complications include preterm birth, low birthweight, and other perinatal adverse outcomes. To mitigate the risks associated with multiple pregnancy, eSET is recommended by international and national professional organizations as the preferred approach in ART. STUDY DESIGN, SIZE, DURATION: The guideline was developed according to the structured methodology for development and update of ESHRE guidelines. Literature searches were performed in PUBMED/MEDLINE and Cochrane databases, and relevant papers published up to May 2023, written in English, were included. Live birth rate, cumulative live birth rate, and multiple pregnancy rate were considered as critical outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Based on the collected evidence, recommendations were discussed until a consensus was reached within the Guideline Development Group (GDG). A stakeholder review was organized after the guideline draft was finalized. The final version was approved by the GDG and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE: The guideline provides 35 recommendations on the medical and non-medical risks associated with multiple pregnancies and on the clinical and embryological factors to be considered when deciding on the number of embryos to transfer. These recommendations include 25 evidence-based recommendations, of which 24 were formulated as strong recommendations and one as conditional, and 10 good practice points. Of the evidence-based recommendations, seven (28%) were supported by moderate-quality evidence. The remaining recommendations were supported by low (three recommendations; 12%), or very low-quality evidence (15 recommendations; 60%). Owing to the lack of evidence-based research, the guideline also clearly mentions recommendations for future studies. LIMITATIONS, REASONS FOR CAUTION: The guideline assessed different factors one by one based on existing evidence. However, in real life, clinicians' decisions are based on several prognostic factors related to each patient's case. Furthermore, the evidence from randomized controlled trials is too scarce to formulate high-quality evidence-based recommendations. WIDER IMPLICATIONS OF THE FINDINGS: The guideline provides health professionals with clear advice on best practice in the decision-making process during IVF/ICSI, based on the best evidence currently available, and recommendations on relevant information that should be communicated to patients. In addition, a list of research recommendations is provided to stimulate further studies in the field. STUDY FUNDING/COMPETING INTEREST(S): The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, the literature searches, and the dissemination of the guideline. The guideline group members did not receive payment. DPB declared receiving honoraria for lectures from Merck, Ferring, and Gedeon Richter. She is a member of ESHRE EXCO, and the Mediterranean Society for reproductive medicine and the president of the Croatian Society for Gynaecological Endocrinology and Reproductive Medicine. CDG is the past Chair of the ESHRE EIM Consortium and a paid deputy member of the Editorial board of Human Reproduction. IR declared receiving reimbursement from ESHRE and EDCD for attending meetings. She holds an unpaid leadership role in OBBCSSR, ECDC Sohonet, and AER. KAR-W declared receiving grants for clinical researchers and funding provision to the institution from the Swedish Cancer Society (200170F), the Senior Clinical Investigator Award, Radiumhemmets Forskningsfonder (Dnr: 201313), Stockholm County Council FoU (FoUI-953912) and Karolinska Institutet (Dnr 2020-01963), NovoNordisk, Merck and Ferring Pharmaceuticals. She received consulting fees from the Swedish Ministry of Health and Welfare. She received honoraria from Roche, Pfizer, and Organon for chairmanship and lectures. She received support from Organon for attending meetings. She participated in advisory boards for Merck, Nordic countries, and Ferring. She declared receiving time-lapse equipment and grants with payment to institution for pre-clinical research from Merck pharmaceuticals and from Ferring. SS-R received research funding from Roche Diagnostics, Organon/MSD, Theramex, and Gedeo-Richter. He received consulting fees from Organon/MSD, Ferring Pharmaceuticals, and Merck Serono. He declared receiving honoraria for lectures from Ferring Pharmaceuticals, Besins, Organon/MSD, Theramex, and Gedeon Richter. He received support for attending Gedeon Richter meetings and participated in the Data Safety Monitoring Board of the T-TRANSPORT trial. He is the Deputy of ESHRE SQART special interest group. He holds stock options in IVI Lisboa and received equipment and other services from Roche Diagnostics and Ferring Pharmaceuticals. KT declared receiving payment for honoraria for giving lectures from Merck Serono and Organon. She is member of the safety advisory board of EDQM. She holds a leadership role in the ICCBBA board of directors. ZV received reimbursement from ESHRE for attending meetings. She also received research grants from ESHRE and Juhani Aaltonen Foundation. She is the coordinator of EHSRE SQART special interest group. The other authors have no conflicts of interest to declare. DISCLAIMER: This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose (full disclaimer available at https://www.eshre.eu/Guidelines-and-Legal).

Relationship between lead concentration in maternal and umbilical cord blood and some neonatal outcomes in primiparous opium-dependent mothers in Zahedan, Southeast of Iran in 2022.

BACKGROUND: There are limited studies on maternal and umbilical cord blood lead levels and their relationship with each other and with pregnancy outcomes in women addicted to opium. The present study was conducted with the aim of investigating the relationship between lead concentrations in maternal blood and umbilical cord blood with some neonatal outcomes in primiparous opium-dependent mothers. METHOD: The present study is a cross-sectional and analytical research. A total of 35 mothers addicted to opium and 35 women without addiction from Zahedan city of Iran participated in this study in 2022. Convenience sampling was done, lead levels were measured and pregnancy outcomes checked by a checklist to collect information. Data analysis was done by independent t-tests, Pearson's correlation coefficient, Point-Biserial Correlation Coefficient, multivariate linear regression and multivariate logistic regression using SPSS version 26 software. RESULTS: There was a significant difference in maternal blood lead levels (24.97 ± 8.45 in addicted mothers and 7.5 ± 4.25 in healthy mothers) and in umbilical cord blood lead concentrations (18.68 ± 6.95 in the addicted group and 5.7 ± 2.84 in the healthy group) between the two groups (P < 0.0001 and P < 0.0001, respectively).The lead concentration of all the samples in the addicted group was higher than the high-risk levels. Birth weight, Apgar score, admission to NICU and need for resuscitation were significantly different between the two groups (P < 0.0001, P < 0.0001, p = 0.03 and p = 0.04, respectively). Based on the results of multivariate linear regression test, only addiction can reversely predict the birth weight (Beta= -0.74, P < 0.0001), 1-minute Apgar score (Beta = -0.47, P = 0.004) and 5th minute (Beta= -0.62, P = 0.001). According to multivariate logistic regression test, OR of none of the predictor variables was significant with the outcomes. Maternal and umbilical cord blood lead concentrations were not predictors of pregnancy outcomes. CONCLUSION: The use of opium during pregnancy leads to an increase in the level of lead in maternal blood and umbilical cord blood. Addiction increased adverse pregnancy outcomes but lead concentration did not predict pregnancy complications. It is recommended that the addiction treatment program be included in pre-pregnancy and pregnancy care plans.

Effectiveness of Arsenicum album 30C in Prevention of COVID-19 in Individuals Residing in Containment Zones of Delhi-A Prospective, Community-based, Parallel Cohort Study.

OBJECTIVE: This work was undertaken to evaluate the protective effect of Arsenicum album 30C against COVID-19. DESIGN: The work was designed as a prospective parallel cluster cohort study. INTERVENTION: Participants were enrolled in a homeopathy intervention (HI) cohort (who received Arsenicum album) or in a non-intervention (NI) cohort (who received no systematic intervention) from COVID-19 containment areas of Delhi. Individuals of age 5 years or above were given four medicated pills of Arsenicum album 30C, while those from 1 to 5 years old were given two medicated pills in each dose. RESULTS: The analysis included 10,180 individuals residing in 11 COVID-19 containment areas in Delhi, out of which 6,590 individuals were in the HI cohort and 3,590 individuals were in the NI cohort. The overall protective effect of Arsenicum album 30C was 83.43% (95% confidence interval [CI], 76.77 to 88.17): 45 cases per 6,590 (8.34 per 10,000 person-weeks) in the Arsenicum album 30C group versus 143 cases per 3,590 (45.01 per 10,000 person-weeks) in the NI cohort. The protective effect of Arsenicum album 30C against laboratory confirmed COVID-19 was 74.40% (95% CI, 55.08 to 85.41): 18 cases per 6,590 (3.32 per 10,000 person-weeks) in the Arsenicum album 30C group versus 38 cases per 3,590 (11.85 per 10,000 person-weeks) in the NI cohort. CONCLUSION: The use of Arsenicum album 30C was associated with some protection against probable and laboratory-confirmed COVID-19 in a containment-zone setting. Randomized controlled trials are needed to confirm or refute these results.

Elevated serum lead levels in neonates born to mothers suffering from opiate use disorder.

BACKGROUND: This study was performed to investigate lead levels in neonates born to the mothers suffering from opiate use disorder (OUD) and the association of lead levels with the Apgar score. METHODS: The present cross-sectional study included 56 neonates who were referred to the neonatal ward of Amir-Al Momenin Hospital, Zabol. The neonates were divided into two groups: the neonates whose mothers suffered OUD and the control group. Data were collected using a researcher-prepared questionnaire, and blood lead level was determined using the atomic absorption method. Data were statistically analyzed. RESULTS: In all, 56 neonates (28 from OUD mothers and 28 from the control mothers) were included in this study. Among the women with OUD, 16 (57%) used inhaled opium, while 12 (43%) consumed opium orally. There was a significant difference regarding Apgar score (9.76 ± 2.11 versus. 7.11 ± 4.21; p = 0.02) and the neonate's blood lead level (2.33 ± 1.3 µg/dl versus 7.33 ± 5.9 µg/dl) between the control and OUD groups (p < 0.001). The odds ratio of abnormally elevated blood lead level rose with increasing duration of maternal opiate disorder for opiate usage durations of 3 to 5 years (adjusted odds ratio [OR] 42.82, 95% confidence interval [CI] 3.27-561, p = 0.004) and > 5 years (adjusted OR 45.5, 95% CI 2.97-698, p = 0.006). CONCLUSION: The results of this study suggested a significant relationship between maternal opium consumption during pregnancy and neonatal serum lead levels, as well as decreased neonatal Apgar score.

Determination of epidemiological characteristics of addicts treated in drug addiction clinics in Kabul.

According to the Afghanistan Ministry of Health, 3.5 million people use drugs, 2.4 million of which are regular users. In this cross-sectional study, it was aimed to determine epidemiological characteristics of addicts in a treatment center in Kabul. Eight hundred people were included. Statistical analysis was done with SPSS 22.0. The average age was 30.74 years, 88.9% were male, and 50.6% were married. Further, 35.9% have never been trained, 60.5% of participants were living in urban areas, 62.8% were refugees, 17.5% were unemployed, and 30.3% of them had monthly income below 147.1 USD. The average age of starting substance use was 19.9 years. "Friendship environment" was the leading reason to start (36.6%), followed by "reduce troubles" with 22.3%. The most preferred substance was cannabis (46.0%), followed by opium (25.3%) and heroin (17.0%). Heroin was the most commonly used substance lifelong (87.1%), followed by cannabis (66.3%) and opium (65.5%). When compared to individuals younger than 18, heroin use rates were 3.52 times higher in the 18-to-30 age range, 5.49 times higher in the 31-to-45 age range, and 1.86 times higher in urban residents than rural. Cannabis use was 12.24 times more among men than women, 2.79 times higher among divorced or widowed individuals than singles, 1.68 times higher among refugees than non-refugees, and 2.26 times higher among drug traffickers than non-traffickers. Opium use was 1.63 times higher for refugees than non-refugees and 3.24 times higher in those who worked in drug fields than those who did not. Periodic assessment of prevalence of drug use and the establishment of drug use monitoring systems are recommended.

A systematic review of clinical and laboratory findings of lead poisoning: lessons from case reports.

Lead is one of the most toxic heavy metals in the environment. The present review aimed to highlight hazardous pollution sources, management, and review symptoms of lead poisonings in various parts of the world. The present study summarized the information available from case reports and case series studies from 2009 to March 2020 on the lead pollution sources and clinical symptoms. All are along with detoxification methods in infants, children, and adults. Our literature compilation includes results from 126 studies on lead poisoning. We found that traditional medication, occupational exposure, and substance abuse are as common as previously reported sources of lead exposure for children and adults. Ayurvedic medications and gunshot wounds have been identified as the most common source of exposure in the United States. However, opium and occupational exposure to the batteries were primarily seen in Iran and India. Furthermore, neurological, gastrointestinal, and hematological disorders were the most frequently occurring symptoms in lead-poisoned patients. As for therapeutic strategies, our findings confirm the safety and efficacy of chelating agents, even for infants. Our results suggest that treatment with chelating agents combined with the prevention of environmental exposure may be an excellent strategy to reduce the rate of lead poisoning. Besides, more clinical studies and long-term follow-ups are necessary to address all questions about lead poisoning management.

Opioid treatment for opioid withdrawal in newborn infants.

BACKGROUND: Neonatal abstinence syndrome (NAS) due to opioid withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss, seizures and neurodevelopmental problems. OBJECTIVES: To assess the effectiveness and safety of using an opioid for treatment of NAS due to withdrawal from opioids in newborn infants. SEARCH METHODS: We ran an updated search on 17 September 2020 in CENTRAL via Cochrane Register of Studies Web and MEDLINE via Ovid. We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for eligible trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi- and cluster-RCTs which enrolled infants born to mothers with opioid dependence and who were experiencing NAS requiring treatment with an opioid. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trial eligibility and risk of bias, and independently extracted data. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included 16 trials (1110 infants) with NAS secondary to maternal opioid use in pregnancy. Seven studies at low risk of bias were included in sensitivity analysis. Opioid versus no treatment / usual care: a single trial (80 infants) of morphine and supportive care versus supportive care alone reported no difference in treatment failure (risk ratio (RR) 1.29, 95% confidence interval (CI) 0.41 to 4.07; very low certainty evidence). No infant had a seizure. The trial did not report mortality, neurodevelopmental disability and adverse events. Morphine increased days hospitalisation (mean difference (MD) 15.00, 95% CI 8.86 to 21.14; very low certainty evidence) and treatment (MD 12.50, 95% CI 7.52 to 17.48; very low certainty evidence), but decreased days to regain birthweight (MD -2.80, 95% CI -5.33 to -0.27) and duration (minutes) of supportive care each day (MD -197.20, 95% CI -274.15 to -120.25). Morphine versus methadone: there was no difference in treatment failure (RR 1.59, 95% CI 0.95 to 2.67; 2 studies, 147 infants; low certainty evidence). Seizures, neonatal or infant mortality and neurodevelopmental disability were not reported. A single study reported no difference in days hospitalisation (MD 1.40, 95% CI -3.08 to 5.88; 116 infants; low certainty evidence), whereas data from two studies found an increase in days treatment (MD 2.71, 95% CI 0.22 to 5.21; 147 infants; low certainty) for infants treated with morphine. A single study reported no difference in breastfeeding, adverse events, or out of home placement. Morphine versus sublingual buprenorphine: there was no difference in treatment failure (RR 0.79, 95% CI 0.36 to 1.74; 3 studies, 113 infants; very low certainty evidence). Neonatal or infant mortality and neurodevelopmental disability were not reported. There was moderate certainty evidence of an increase in days hospitalisation (MD 11.45, 95% CI 5.89 to 17.01; 3 studies, 113 infants), and days treatment (MD 12.79, 95% CI 7.57 to 18.00; 3 studies, 112 infants) for infants treated with morphine. A single adverse event (seizure) was reported in infants exposed to buprenorphine. Morphine versus diluted tincture of opium (DTO): a single study (33 infants) reported no difference in days hospitalisation, days treatment or weight gain (low certainty evidence). Opioid versus clonidine: a single study (31 infants) reported no infant with treatment failure in either group. This study did not report seizures, neonatal or infant mortality and neurodevelopmental disability. There was low certainty evidence for no difference in days hospitalisation or days treatment. This study did not report adverse events. Opioid versus diazepam: there was a reduction in treatment failure from use of an opioid (RR 0.43, 95% CI 0.23 to 0.80; 2 studies, 86 infants; low certainty evidence). Seizures, neonatal or infant mortality and neurodevelopmental disability were not reported. A single study of 34 infants comparing methadone versus diazepam reported no difference in days hospitalisation or days treatment (very low certainty evidence). Adverse events were not reported. Opioid versus phenobarbital: there was a reduction in treatment failure from use of an opioid (RR 0.51, 95% CI 0.35 to 0.74; 6 studies, 458 infants; moderate certainty evidence). Subgroup analysis found a reduction in treatment failure in trials titrating morphine to ≧ 0.5 mg/kg/day (RR 0.21, 95% CI 0.10 to 0.45; 3 studies, 230 infants), whereas a single study using morphine < 0.5 mg/kg/day reported no difference compared to use of phenobarbital (subgroup difference P = 0.05). Neonatal or infant mortality and neurodevelopmental disability were not reported. A single study (111 infants) of paregoric versus phenobarbital reported seven infants with seizures in the phenobarbital group, whereas no seizures were reported in two studies (170 infants) comparing morphine to phenobarbital. There was no difference in days hospitalisation or days treatment. A single study (96 infants) reported no adverse events in either group. Opioid versus chlorpromazine: there was a reduction in treatment failure from use of morphine versus chlorpromazine (RR 0.08, 95% CI 0.01 to 0.62; 1 study, 90 infants; moderate certainty evidence). No seizures were reported in either group. There was low certainty evidence for no difference in days treatment. This trial reported no adverse events in either group. None of the included studies reported time to control of NAS. Data for duration and severity of NAS were limited, and we were unable to use these data in quantitative synthesis. AUTHORS' CONCLUSIONS: Compared to supportive care alone, the addition of an opioid may increase duration of hospitalisation and treatment, but may reduce days to regain birthweight and the duration of supportive care each day. Use of an opioid may reduce treatment failure compared to phenobarbital, diazepam or chlorpromazine. Use of an opioid may have little or no effect on duration of hospitalisation or treatment compared to use of phenobarbital, diazepam or chlorpromazine. The type of opioid used may have little or no effect on the treatment failure rate. Use of buprenorphine probably reduces duration of hospitalisation and treatment compared to morphine, but there are no data for time to control NAS with buprenorphine, and insufficient evidence to determine safety. There is insufficient evidence to determine the effectiveness and safety of clonidine.

Data Collection during the COVID-19 Pandemic: Learning from Experience, Resulting in a Bayesian Repertory.

BACKGROUND: A novel pandemic disease offered the opportunity to create new, disease-specific, symptom rubrics for the homeopathic repertory. OBJECTIVE: The aim of this study was to discover the relationship between specific symptoms and specific medicines, especially of symptoms occurring frequently in this disease. MATERIALS AND METHODS: Worldwide collection of data in all possible formats by various parties was coordinated by the Liga Medicorum Homeopathica Internationalis. As the data came in, more symptoms were assessed prospectively. Frequent analysis and feedback by electronic newsletters were used to improve the quality of the data. Likelihood ratios (LRs) of symptoms were calculated. An algorithm for combining symptom LRs was programmed and published in the form of an app. The app was tested against 18 well-described successful cases from Hong Kong. RESULTS: LRs of common symptoms such as 'Fatigue' and 'Headache' provided better differentiation between medicines than did existing repertory entries, which are based only on the narrow presence or absence of symptoms. A mini-repertory for COVID-19 symptoms was published and supported by a web-based algorithm. With a choice of 20 common symptoms, this algorithm produced the same outcome as a full homeopathic analysis based upon a larger number of symptoms, including some that are traditionally considered more specific to particular medicines. CONCLUSION: A repertory based on clinical data and LRs can differentiate between homeopathic medicines using a limited number of frequently occurring epidemic symptoms. A Bayesian computer algorithm to combine symptoms can complement a full homeopathic analysis of cases.

A cross-sectional study of errors in physicians orders' of antiseizure medications among people with epilepsy from rural India.

AIMS: To enumerate and classify errors in physicians' orders of antiseizure medications (ASMs) to people with epilepsy presenting to neurology clinic. METHODS: This cross-sectional study was conducted in the neurology clinic of a teaching hospital catering to a predominantly rural population. People in whom a diagnosis of epilepsy was confirmed and who presented for the first time with a prior prescription for antiseizure medication/s were included. Their immediate previous prescriptions were assessed for errors, enumerated and classified according to WHO guidelines for prescription writing. RESULTS: Hundred prescriptions of 334 patients screened were analyzed. The number of ASMs prescribed to a participant was 2 ±â€¯0.6 (mean ±â€¯SD). We identified a mean of 5 ±â€¯4 (median: 3; range: 1-7) errors in each order. These included superscription errors, e.g., missing information on seizure control and frequency (n = 90, 90%), generic name (n = 62, 62%), patient identifiers (n = 57, 57%), prescribers' identifiers (n = 29, 29%) and diagnosis or indication for prescribing the medication/s (n = 55, 55%). The most common inscription and subscription errors were dosing errors (22%) and pharmaceutical form errors (20%) followed by omission (13%), duplication (13%), substitution (12%), commission (9%) and frequency errors (8%). Errors were more common among prescriptions provided by primary-care and Ayurvedic, Yoga and Naturopathy, Unani, Siddha and Homeopathy (AYUSH) physicians compared to specialists (P < 0.05). CONCLUSIONS: Errors are common among medication orders provided by non-specialist and specialist physicians. Primary care and AYUSH are more liable to make errors underscoring the need to educate them in basic epilepsy treatment.

Nineteenth-Century Homeopathic Repertories Predict Increased Urinary Excretion of Bile in Cholestasis but Not in Non-Cholestatic Infant Jaundice.

INTRODUCTION: There are two types of bilirubin: conjugated bilirubin, prevalent in cholestatic jaundice, and unconjugated bilirubin, prevalent in hematologic jaundice. Conjugated bilirubin is water soluble and is excreted in urine, whereas unconjugated bilirubin is neither water soluble nor excreted in urine. Homeopathic repertories published prior to the discovery of the two types of bilirubin in 1913 present an opportunity to test the reliability of homeopathic repertories and associated materia medica. If procedures involved in the collecting of homeopathic observations are reliable, then in repertories published prior to 1913, medicines listed for cholestatic jaundice should exhibit a stronger association with urine bile than medicines listed for hematologic jaundice. MATERIALS AND METHODS: In three repertories published prior to 1913, medicines associated with jaundice were further classified into groups labeled "Cholestatic" or "Infant, mostly hematologic". Medicines were identified as "Cholestatic" if associated with both white/clay-colored stool and liver/gallbladder symptoms. Medicines were identified as "Infant, mostly hematologic" if associated with infant jaundice without meeting criteria for the "Cholestatic" group. Controls were medicines appearing in Hahnemann's Materia Medica Pura. Each category was assessed for green urine-usually reflective of bile in urine. RESULTS: In Knerr's repertory, the "Cholestatic" group demonstrated a significantly greater association with green urine than controls (p < 0.05, Fisher's exact test), whereas the "Infant, mostly hematologic" group did not differ significantly from controls. For Lippe's and Boenninghausen's repertories, statistical significance was not demonstrated. Across repertories, the overall weighted pooled odds ratio (OR) demonstrated significance in the association between the "Cholestatic" group and green urine (OR, 2.384; 95% confidence interval, 1.234 to 4.607), whereas the "Infant, mostly hematologic" group was similar to that of controls (OR, 0.754; 95% confidence interval, 0.226 to 2.514). CONCLUSIONS: Based on the presence or absence of bile in the urine, homeopathic repertories from the 19th century can distinguish between disease processes involving conjugated bilirubin and disease processes involving unconjugated bilirubin.

Electronic Registration in Complementary/Homeopathic Medical Practice with Identification of 'Best Homeopathic Cases': A Pilot Study.

BACKGROUND: Practice-based registration could identify 'general' and 'homeopathic' prognostic factors for therapeutic success in patients who seek complementary and alternative medicine (CAM)/homeopathic treatment. Identification of 'best homeopathic cases' within a database could inform clinical research and improve homeopathic practice. OBJECTIVE: To investigate the feasibility of registration in daily CAM/homeopathic practice, evaluate patient-reported outcome measures and tools for identifying 'best homeopathic cases' and to make recommendations for an electronic database. METHODS: In 2015 and 2016, 25 homeopathic doctors registered details of a maximum of 20 patients each, with 6 months of follow-up (extended follow-up for 'best homeopathic cases'), in Excel or in the Homeopathic Administration and Registration Program (HARP) database. Informed consent was obtained from each patient. Patient-perceived change of main complaint was measured by a 7-point Likert scale. Best homeopathic cases were defined by treatment with one homeopathic medicine, ≥ 2 months of follow-up, result score +2 to +4 on a 9-point Likert scale by the doctor, and by changes that could be attributed to the homeopathic medicine. Association between scores for change of main complaint and scores for 'best homeopathic case' was analysed by the Kruskal gamma test. RESULTS: Three-hundred and ninety-nine patients were included. In 49.1%, the main complaint was present for ≥ 2 years. The most common diagnosis was 'fatigue' (N = 56; 14%). Major improvement in the main complaint (score +3) was reported by 22 to 26% at consecutive follow-up visits. One-hundred and ninety-six patients were treated with a single homeopathic medicine, among whom 66 'best homeopathic cases' were identified. The correlation between patient-reported changes of main complaint and assessment by the doctor was significant (gamma = 0.832; p < 0.001). CONCLUSIONS: Registration of (co-)diagnoses, chronicity, treatments and outcomes in homeopathic practice with identification of 'best homeopathic cases' is feasible, using the tools provided. A user-friendly electronic database for efficient recording is recommended.

The role of domain-general cognitive resources in children's construction of a vitalist theory of biology.

Some episodes of learning are easier than others. Preschoolers can learn certain facts, such as "my grandmother gave me this purse," only after one or two exposures (easy to learn; fast mapping), but they require several years to learn that plants are alive or that the sun is not alive (hard to learn). One difference between the two kinds of knowledge acquisition is that hard cases often require conceptual construction, such as the construction of the biological concept alive, whereas easy cases merely involve forming new beliefs formulated over concepts the child already has (belief revision, a form of knowledge enrichment). We asked whether different domain-general cognitive resources support these two types of knowledge acquisition (conceptual construction and knowledge enrichment that supports fast mapping) by testing 82 6-year-olds in a pre-training/training/post-training study. We measured children's improvement in an episode involving theory construction (the beginning steps of acquisition of the framework theory of vitalist biology, which requires conceptual change) and in an episode involving knowledge enrichment alone (acquisition of little known facts about animals, such as the location of crickets' ears and the color of octopus blood). In addition, we measured children's executive functions and receptive vocabulary to directly compare the resources drawn upon in the two episodes of learning. We replicated and extended previous findings highlighting the differences between conceptual construction and knowledge enrichment, and we found that Executive Functions predict improvement on the Vitalism battery but not on the Fun Facts battery and that Receptive Vocabulary predicts improvement the Fun Facts battery but not on the Vitalism battery. This double dissociation provides new evidence for the distinction between the two types of knowledge acquisition, and bears on the nature of the learning mechanisms involved in each.

Homeopathic medicinal products for preventing and treating acute respiratory tract infections in children.

BACKGROUND: Acute respiratory tract infections (ARTIs) are common and may lead to complications. Most children experience between three and six ARTIs annually. Although these infections are self-limiting, symptoms can be distressing. Many treatments are used to control symptoms and shorten illness duration. Most have minimal benefit and may lead to adverse effects. Oral homeopathic medicinal products could play a role in childhood ARTI management if evidence for effectiveness is established. OBJECTIVES: To assess the effectiveness and safety of oral homeopathic medicinal products compared with placebo or conventional therapy to prevent and treat acute respiratory tract infections in children. SEARCH METHODS: We searched CENTRAL (2017, Issue 11) including the Cochrane Acute Respiratory Infections Specialised Register, MEDLINE (1946 to 27 November 2017), Embase (2010 to 27 November 2017), CINAHL (1981 to 27 November 2017), AMED (1985 to December 2014), CAMbase (searched 29 March 2018), British Homeopathic Library (searched 26 June 2013 - no longer operating). We also searched the WHO ICTRP and ClinicalTrials.gov trials registers (29 March 2018), checked references, and contacted study authors to identify additional studies. SELECTION CRITERIA: Double-blind, randomised controlled trials (RCTs) or double-blind cluster-RCTs comparing oral homeopathy medicinal products with identical placebo or self-selected conventional treatments to prevent or treat ARTIs in children aged 0 to 16 years. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included eight RCTs of 1562 children receiving oral homeopathic medicinal products or a control treatment (placebo or conventional treatment) for upper respiratory tract infections (URTIs). Four treatment studies examined the effect on URTI recovery, and four studies investigated the effect on preventing URTIs after one to three months of treatment, followed up for the remainder of the year. Two treatment and two prevention studies involved homeopaths individualising treatment. The other studies used predetermined, non-individualised treatments. All studies involved highly diluted homeopathic medicinal products.We found several limitations to the included studies, in particular methodological inconsistencies and high attrition rates, failure to conduct intention-to-treat analysis, selective reporting, and apparent protocol deviations. We assessed three studies as at high risk of bias in at least one domain, and many had additional domains with unclear risk of bias. Three studies received funding from homeopathy manufacturers; one support from a non-government organisation; two government support; one was cosponsored by a university; and one did not report funding support.Methodological inconsistencies and significant clinical and statistical heterogeneity precluded robust quantitative meta-analysis. Only four outcomes were common to more than one study and could be combined for analysis. Odds ratios (OR) were generally small with wide confidence intervals (CI), and the contributing studies found conflicting effects, so there was little certainty that the efficacy of the intervention could be ascertained. All studies assessed as at low risk of bias showed no benefit from oral homeopathic medicinal products; trials at uncertain and high risk of bias reported beneficial effects.We found low-quality evidence that non-individualised homeopathic medicinal products confer little preventive effect on ARTIs (OR 1.14, 95% CI 0.83 to 1.57). We found low-quality evidence from two individualised prevention studies that homeopathy has little impact on the need for antibiotic usage (N = 369) (OR 0.79, 95% CI 0.35 to 1.76). We also assessed adverse events, hospitalisation rates and length of stay, days off school (or work for parents), and quality of life, but were not able to pool data from any of these secondary outcomes.There is insufficient evidence from two pooled individualised treatment studies (N = 155) to determine the effect of homeopathy on short-term cure (OR 1.31 favouring placebo, 95% CI 0.09 to 19.54; very low-quality evidence) and long-term cure rates (OR 0.99, 95% CI 0.10 to 9.67; very low-quality evidence). Adverse events were reported inconsistently; however, serious events were not reported. One study found an increase in the occurrence of non-severe adverse events in the treatment group. AUTHORS' CONCLUSIONS: Pooling of two prevention and two treatment studies did not show any benefit of homeopathic medicinal products compared to placebo on ARTI recurrence or cure rates in children. We found no evidence to support the efficacy of homeopathic medicinal products for ARTIs in children. Adverse events were poorly reported, so conclusions about safety could not be drawn.

Whooping Cough Alleviated by Homeopathic Medicines: A Case Report.

Context • Pertussis cough (whooping cough) is distressing due to the intensity and chronicity of its cough. No specific drugs are available that can alleviate the cough's intensity or significantly shorten its duration. Homeopathic medicines are used for a wide variety of medical conditions, including cough. Objective • The study investigated the benefits of homeopathic medicines for whooping cough, to alleviate the cough's intensity and to shorten its duration. Design • The current study was a case series of patients with whooping cough. Setting • The study took place at one of the suburban hospital clinics of the Ann & Robert H. Lurie Children's Hospital of Chicago (Chicago, IL, USA). Participants • Participants were 20 patients aged 21 mo to 20 y, of whom 11 were female and 18 were male, who visited the hospital clinic for treatment of the chronic cough that is characteristic of whooping cough. The details of the cases of 3 representative participants are highlighted in the text. Intervention • The 3 representative patients all received 1 dose weekly of a 30c dilution of homeopathic pertussinum and a 6c dilution of homeopathic Drosera 3 times daily. The homeopathic medicines most often used for the other participants were the same doses of pertussinum and Drosera. Outcome Measures • Verbal feedback from patient or family were obtained at the follow-up visits. Results • The intensity and duration of participant's coughs were alleviated within days to 1 wk in most cases. Conclusions • Homeopathic medicines can alleviate the intensity or reduce the duration of whooping cough, with no adverse effects.

A Pilot Study of Prospective Data Collection by Italian Homeopathic Doctors.

OBJECTIVE: The main purpose of this article is to report the systematic data collection pertaining to the consultations of a group of qualified homeopathic physicians. Studies have been performed concerning: (1) the most frequently treated pathologies; (2) the symptoms reported by patients, with a particular focus on "fear" symptoms; and (3) the evaluation of the outcomes of the treatment, including likelihood ratio (LR) for fear symptoms of mostly prescribed remedies. DESIGN: Prospective observational study. SETTING: Individualized homeopathic treatment at private homeopathic surgeries in Italy. PARTICIPANTS: Adult patients asking for homeopathic therapy for a series of common ailments. OUTCOME MEASURES: Types of diseases and remedies used and clinical parameters (frequency of acute attacks, and their intensity and duration); the overall outcome of the cure was registered using the Outcome Related to Impact on Daily Living (ORIDL) scale. RESULTS: Only 94 patients could be enrolled by eight homeopathic doctors in a 2-year period between 2015 and 2017. Ninety (72 females, 18 males) patients completed the observation period. The most represented pathologies belonged to the group "Anxiety and anxiety disorders" followed by gastrointestinal ailments. The most prescribed remedy was Phosphorus (9 cases), followed by Natrum muriaticum (4 cases) and Ignatia (4 cases). The intensity of the symptoms and the frequency of the attacks decreased during the course of the study. Most patients reported a positive outcome (ORIDL scale). In the "Phosphorus" group, LR values were calculated for fear symptoms: LR+ for fear of dark = 2.25 (95% confidence interval [CI] = 0.56 to 9.02), LR- for fear of crowds = 1.27 (95% CI = 1.13 to 1.42), and LR- for fear of ghosts = 1.12 (95% CI = 1.04 to 1.22). CONCLUSION: The recruited group was smaller than expected, but data from most participants could be collected. Positive clinical outcomes were recorded and LR of a few specific fears contributed to distinguish Phosphorus patients from the remaining population.

[Teething: from symptomatology to practical approach].

Scopo della presente trattazione è promuovere la consapevolezza del pediatra nei confronti della sintomatologia legata alla dentizione nei bambini con il supporto delle evidenze più significative reperibili nella letteratura scientifica. Dopo la caratterizzazione dei disturbi più comuni, con la relativa incidenza e durata nella popolazione pediatrica, e del ruolo dell'infiammazione saranno definiti i limiti delle terapie attualmente disponibili. Saranno quindi illustrate le prerogative di un medicinale omeopatico, Camilia® (Boiron, Francia), che interviene sull'infiammazione locale e sistemica e sulla composita fenomenologia correlata al processo di dentizione, con il vantaggio di un'azione multifunzionale ed efficace e l'assenza di effetti indesiderati o rischi di interazione con altri farmaci.

Symptoms associated with teething and response to three treatments, including homeopathic medicine: a multicenter prospective observational study among 190 French pediatricians.

BACKGROUND: Primary tooth eruption in infants is associated with a range of local and systemic symptoms although this remains a subject of much debate. In addition, data are limited on the role of physicians in managing infant teething, and on the benefit of homeopathic treatments. METHODS: We conducted an observational, multicenter, prospective survey evaluating teething symptoms, and symptom course following routine medical management by French pediatricians in 597 infants aged from 3 to 24 months. We also examined the response to treatment with routinely prescribed teething medications; the homeopathic agent, Camilia® and topically applied gingival agents (Delabarre® or Dolodent®). RESULTS: Most infants (96.6%) had buccogingival symptoms and 93.3% had at least one general symptom. Fever (≥38 °C) was reported in 15.2% of infants. For teething, 212 infants were prescribed Camilia®, 172 a gingival solution (Delabarre® or Dolodent®) and 213 received Camilia® along with a gingival agent. Infants prescribed both a homeopathic and a gingival treatment had a significantly higher number of symptoms at presentation compared with those prescribed a single agent. There were no significant differences in symptom course across these three treatment groups. Systemic analgesics/antipyretics were prescribed in 68.8% of cases. Parent satisfaction with medical management and prescribed treatments was high. CONCLUSIONS: Teething is frequently associated with transient local and systemic upset in infants and is a significant concern to parents. Camilia® provides a similar benefit to topical therapy, and is frequently used by pediatricians in France.

Longitudinal follow-up in female Childhood Cancer Survivors: no signs of accelerated ovarian function loss.

STUDY QUESTION: Is the long-term decline of ovarian function, as reflected by a decrease in serum anti-Müllerian hormone (AMH) concentration, accelerated over time in female childhood cancer survivors (CCS) as compared to healthy women of the same age? SUMMARY ANSWER: The median decline of AMH levels in long-term female CCS is not accelerated and similar to that observed in healthy controls. WHAT IS KNOWN ALREADY: Gonadal function is compromised in female CCS treated with chemotherapy and/or radiation therapy. Ovarian function is most compromised in survivors treated with total body irradiation, abdominal or pelvic irradiation, stem cell transplantation or high doses of alkylating agents. STUDY DESIGN SIZE, DURATION: Longitudinal single-centre cohort study in 192 CCS in Rotterdam, The Netherlands, between 2001 and 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum AMH levels of 192 adult female CCS were assessed, at least five years after cessation of treatment and at a follow-up visit with a median of 3.2 years (range: 2.1-6.0) later and were compared to the age-based P50 of AMH in healthy controls. MAIN RESULTS AND THE ROLE OF CHANCE: Median AMH levels were below the P50 at both visit 1 (-0.59 µg/L) and at visit 2 (-0.22 µg/L). In women with a sustained ovarian function (AMH > 1.0 µg/L), the decline in AMH is similar to that in the normal population (difference in decline per year: -0.07 µg/L (range: -2.86 to 4.92), P  = 0.75). None of the treatment modalities was correlated with a significant acceleration of decline of AMH per year. LIMITATIONS REASONS FOR CAUTION: We selected CCS that visited our late effect outpatient clinic and who had two AMH levels available. It is conceivable that women without any apparent late effects of treatment as well as women with extreme late effects, which might be the ones with the largest impact on ovarian function, could be more likely to be lost to follow-up. However, general characteristics did not differ between the included and excluded patients. WIDER IMPLICATIONS OF THE FINDINGS: While prospective longitudinal research is required to strengthen our findings, they may help physicians to counsel female CCS about their expected reproductive lifespan. STUDY FUNDING/COMPETING INTERESTS: A.L.F.v.d.K., M.M.v.d.H.-E. and S.M.F.P. are supported by FP7-PanCare LIFE. J.S.E.L. has received grants from the following companies (in alphabetical order): Ferring, Merck Serono, Merck Sharp and Dome, Organon, Serono, Shering Plough and Shering. The other authors have no conflicts of interest to declare.

Neonatal health including congenital malformation risk of 1072 children born after vitrified embryo transfer.

STUDY QUESTION: Does vitrification of Day 3 and Day 5 embryos adversely affect birth outcomes of singletons and twins in comparison with peers born after fresh embryo transfer? SUMMARY ANSWER: Neonatal health parameters, including the prevalence of congenital malformations, in singletons and twins born after embryo vitrification are similar to or slightly better than after fresh embryo transfer. WHAT IS ALREADY KNOWN: Although vitrification, rather than slow-freezing, of embryos is routine practice nowadays, convincing evidence regarding the safety for the offspring is sparse. Literature data comprise results from mostly small-sized studies or studies including only Day 3 or only Day 5 vitrified embryo transfers. Overall, better or comparable perinatal outcomes, in terms of higher birthweight and lower risk for small-for-gestational age or for low birthweight, have been reported for singletons born after vitrified embryo transfer compared with fresh embryo transfer. According to the single available study with sufficient sample size, the congenital malformation rate was found to be comparable after vitrified and fresh embryo transfers. STUDY DESIGN, SIZE, DURATION: Data were collected from 960 cycles after transfer of embryos vitrified on Day 3 (n = 457) or Day 5 (n = 503) and from 1644 cycles after fresh embryo transfer on Day 3 (n = 853) or Day 5 (n = 791), performed between 2008 and 2013 at the Centre for Reproductive Medicine of the university hospital UZ Brussel. Outcome measures were neonatal health in terms of birthweight, small-for-gestational age, prematurity rate, perinatal death and major/minor/total malformation rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Perinatal health parameters of 11 stillborns and 1061 live borns (827 singletons and 234 twins) in the vitrified group and of 28 stillborns and 1838 live borns (1374 singletons and 464 twins) in the fresh embryo group are reported. Within 3 months after birth, children in the two study groups were assessed clinically with special attention to congenital malformations by a paediatrician blinded to the type of embryo transfer. Data were analysed by multiple linear and logistic regression, adjusted for treatment variables and maternal characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Mothers to infants in the vitrified group were on average slightly older and more often suffering from pregnancy-related hypertensive disorders than mothers to infants in the fresh transfer group. Singletons born after vitrification showed a higher birthweight standard deviation score (SDS) (-0.4 versus -0.7; 95% confidence interval (CI): 0.0-0.3, P = 0.001) and a lower small-for-gestational age rate (AOR: 0.55; 95% CI: 0.34-0.90) in comparison with peers born after fresh embryo transfer. Preterm birth rate and perinatal death rate were comparable between the two groups (AOR: 0.91; 95% CI: 0.57-1.43 and AOR: 0.97; 95% CI: 0.40-2.36). In twins, neonatal outcomes including birthweight SDS, small-for-gestational age and prematurity rates were comparable in the vitrified and the fresh groups, when adjusted for confounders. Furthermore, the rate of major congenital malformations in live borns was comparable between the vitrified group and the fresh group, both in singletons (2.6 versus 2.8%; AOR: 0.91; 95% CI: 0.47-1.78) and in twins (2.4 versus 2.7%; AOR: 0.51; 95% CI: 0.05-5.72). Also, the total malformation rate in the vitrified group (3.4%; 95% CI: 2.4-4.8) did not differ from the rate in the fresh embryo group (3.9%; 95% CI: 3.1-5.0). The embryonic stage at vitrification or fresh transfer (cleavage-stage embryo or blastocyst) did not influence the birth characteristics or malformation rate. LIMITATIONS, REASONS FOR CAUTION: The main limitation of this study is the rather small twin group. Therefore, the outcome results for twins should be interpreted cautiously. WIDER IMPLICATIONS OF THE FINDINGS: This study provides evidence that transfer of vitrified Day 3 and Day 5 embryos does not adversely affect the neonatal health of the offspring in comparison with transfer of fresh embryos. Furthermore, neonatal outcomes were not different after transfer of vitrified blastocysts compared with transfer of vitrified cleavage-stage embryos. STUDY FUNDING/COMPETING INTERESTS: Educational grants for establishing and organizing the data collection have come from IBSA, Ferring, Organon, Shering-Plough and Merck. Merck Belgium funded the data collection for outcomes after vitrification between 2012 and 2015. All co-authors, except M.B., declared no conflict of interest. M.B. has received consultancy fees from Organon, Serono Symposia and Merck.

Maternal use of probiotics during pregnancy and effects on their offspring's health in an unselected population.

Probiotics are used by women in the perinatal period and may improve balance of microbiota, with possible health benefits for both mother and baby. Characteristics and (health) behaviour patterns of mothers using probiotics during pregnancy, and health effects on their offspring, were investigated. Differences between mothers using probiotics during pregnancy and those who did not, were assessed. In total, 341 out of 2491 (13.7%) mothers reported use of probiotics during pregnancy. There were no significant differences in maternal features (gestation, age, ethnicity, education) between users and non-users. Logistic regression analyses showed that consumption of probiotics was significantly associated with use of homeopathic products [odds ratio (OR) 1.65, 95% confidence interval (CI) 1.17-2.33, p = 0.005], maternal history of smoking (OR 1.72, 95% CI 1.25-2.37, p = 0.001) and paternal history of smoking (OR 1.39, 95% CI 1.01-1.89, p = 0.05). Common disease symptoms during the first year of life in the offspring did not differ between both groups. CONCLUSION: The use of probiotics or other health-related products without doctor's prescription during pregnancy might point to compensation for types of less favourable behaviour. Probiotic use during pregnancy does not seem to induce positive health effects in the offspring in an unselected population. WHAT IS KNOWN: Aberrant microbiota compositions have been detected during critical periods when early programming occurs including pregnancy and early neonatal life. Probiotics modulate intestinal microbiota composition and are associated with positive health effects. WHAT IS NEW: The use of probiotics or other health-related products without doctor's prescription during pregnancy is associated with and might point to compensation for types of less favourable behaviour. Probiotic use during pregnancy does not induce positive health effects in the offspring in this unselected population.