In-person (face-to-face) data collection methods offer many advantages but can also be time-consuming and expensive, particularly in areas of difficult access. We take advantage of the increasing mobile phone penetration rate in rural areas to evaluate the feasibility of using cell phones to monitor the provision of key health and nutrition interventions linked to the first 1,000 days of life, a critical period of growth and development. We examine response rates to calendarized text messages (SMS) and phone calls sent to 1,542 households over a period of four months. These households have children under two years old and pregnant women and are located across randomly selected communities in Quiche, Guatemala. We find that the overall  response rate to phone calls is over 5 times higher than to text messages (75.8% versus 14.4%). We also test whether simple SMS reminders improve the timely reception of health services but do not find any effects in this regard. Language, education, and age appear to be major barriers to respond to text messages as opposed to phone calls, and the rate of response is not correlated with a household’s geographic location (accessibility). Moreover, response veracity is high, with an 84–91% match between household responses and administrative records. The costs per monitored intervention are around 1.12 US dollars using text messages and 85 cents making phone calls, with the costs per effective answer showing a starker contrast, at 7.76 and 1.12 US dollars, respectively. Our findings indicate that mobile phone calls can be an effective, low-cost tool to collect reliable information remotely and in real time. In the current context, where in-person contact with households is not possible due to the COVID-19 crisis, phone calls can be a valuable instrument for collecting information, monitoring development interventions, or implementing brief surveys. Development programs and interventions are often implemented across remote, isolated areas. Regular data collection regarding these interventions is essential to conduct appropriate oversight and monitoring, identify bottlenecks and improve ongoing processes, and evaluate outcomes. While in-person (face-to-face) methods offer many advantages, including increased trust between interviewee and interviewer and the possibility to capture detailed responses in complex contexts, they can be expensive, time-consuming, and logistically challenging, particularly in areas of difficult access. In these situations, mobile phones can offer an alternative approach for collecting ground data that is relatively inexpensive and easily scalable. Moreover, in the current context of travel restrictions, lockdowns, and social distancing measures due to the COVID-19 crisis, the use of information and communications technology (ICT) such as mobile phones may represent the only available method for data collection.Such a tool for data collection among disadvantaged populations in generally remote areas has only recently become possible at a large scale. Mobile phone penetration has increased dramatically over the past two decades. Global mobile subscriptions have increased three-fold from 34% of the population in 2005 to 108% in 2019 [This paper evaluates the feasibility of monitoring the provision of health and nutrition interventions in rural, remote areas in the department of Quiche, located in the Western Highlands of Guatemala, by directly engaging with end-users through text messages (henceforth SMS) and calls to their mobile phones. The study is part of a broader collaboration with local stakeholders to develop innovative tools to better monitor and improve maternal and child health and nutrition among vulnerable populations in Guatemala. In this line, the study also aims to assess and validate a monitoring tool that can serve to identify bottlenecks in real time and improve the responsiveness of multiple ongoing interventions remotely. The study builds on an earlier proof of concept study conducted in 2017 in the department of Chiquimula, where similar interventions were exclusively monitored by SMS . We expaTo do this, we directly ask households questions about receipt of scheduled health and nutrition services, either through simple SMS or phone calls, over the course of four months. We also send SMS reminders to a subgroup of households to assess the effects on attending health centers to receive these services. We rely on a cluster randomized controlled trial (cRCT) design to compare the relative effectiveness, as measured by response rates, between these two modes of contact, with and without the provision of reminders. We examine the potential factors correlated with the likelihood of responding, including language and location differences. In addition, we compare direct answers from households with administrative data maintained by the health centers for a subsample of our study group.Monitoring these interventions is highly relevant in both a country and area where food insecurity and chronic malnutrition is a serious problem. Despite its level of Gross Domestic Product (GDP), Guatemala is the Latin American country with the highest chronic malnutrition rate for children aged 0–5 years old 46.5%) and is ranked sixth globally .5% and i–9. We spThe use of ICT on issues related to poverty, health, and nutrition is not new in the literature. One strand of studies has concentrated on evaluating the use of ICT to provide information on prices, pests, diseases, good hygiene practices, and nutrition reminders or warnings to aid better decision-making or promote behavioral changes among the population of interest –19. AnotWe contribute to both strands of the literature by comparing the benefits of two alternative modes of communication  within the same context using experimental methods. We also evaluate the effects of providing SMS reminders to encourage the reception of health and nutrition services among children and pregnant women in remote, rural areas. Similarly, we inform the robustness of such data collection tools in a context of rugged geography and linguistic heterogeneity and offer preliminary evidence on the accuracy and veracity of direct household responses by comparing these with administrative data.The study assesses the use of cell phones to monitor health and nutrition interventions related to the 1,000 Days Window of Opportunity, which are part of the core interventions of the national strategy against malnutrition (ENPDC) in Guatemala. As such, the study focuses on pregnant women and children under two years old and the key health and nutrition interventions they are normally meant to receive from their local public health centers.Participation in the study was strictly voluntary and all participating households gave written, informed consent. The study was approved by the Institutional Review Board of the International Food Policy Research Institute (IFPRI).The study was carried out between November 2018 and June 2019. The study design incorporates lessons learned from a proof of concept study implemented in the department of Chiquimula in 2017. The most important lesson drawn from that study was the difficulty of asking questions over SMS, bringing about the possibility of communicating via phone calls instead, due to (i) a greater ease by households to answer phone calls, (ii) the ability to resolve doubts about the questions asked on the spot during a call, and (iii) the null cost of answering incoming calls in Guatemala. We accordingly decided to incorporate phone calls in the present study.Two other major conclusions from the previous study were that financial incentives  and the number of questions sent  did not turn out to be determining factors in the propensity of households to respond. We thus chose not to reassess these factors in Quiche. Instead, all participating households received the entire set of questions around the health and nutrition interventions that were due, and households that were asked questions through SMS also received monthly airtime top-ups (to avoid liquidity constraints preventing households from responding). Other lessons learned from the proof of concept study were to communicate during weekends (since shared use of a mobile phone within the family implied a lack of access during weekdays) and to exclusively rely on women for contacting households .Finally, following the behavioral change literature using ICTs, an additional purpose of this study was to assess the effects of sending reminders via SMS to encourage individuals to visit the health center to receive interventions. Thus, SMS reminders were sent about a week in advance of the date in which the targeted individual was due to receive a given health or nutrition service according to the official health protocol. Based on these study objectives, we implemented a clustered randomized controlled trial (cRCT), randomly assigning every participating community to one out of four treatment arms, with all households in the community subject to the same treatment. We followed a randomized crossover design along the following dimensions:Mode of contact. Households in half of the selected communities would be asked questions through SMS, while those in the other half of communities would be asked questions through phone calls.Reminders. In addition to the monitoring questions, households in half of the selected communities would be sent SMS reminders for all upcoming health services for the targeted individual during the course of the study and those in the other half would receive just the monitoring questions (by phone or text) but no SMS reminders.This design has the dual advantage of both reducing the possibility of spillovers between treatment arms and simplifying field logistics. The randomization of communities was carried out before fieldwork, such that the field team doing the interviews would know in advance the treatment arm to which a community belonged to and could fully explain to participating households what to expect over the subsequent weeks.The department of Quiche was selected since it was one of the four departments prioritized in the ENPDC and because Mayan languages are spoken across the large majority of its communities, allowing for the assessment of potential linguistic obstacles. In consultation with local actors, the municipalities of Santa Maria Nebaj (hereafter Nebaj) and San Miguel Uspantan (hereafter Uspantan) were selected taking into consideration: (i) the availability of health services, such that sufficient coverage of health services would exist in the selected municipalities to allow for a monitoring scheme; and (ii) the absence of social conflicts, to avoid potential disruptions to fieldwork activities.Due to budget limitations that precluded the possibility of conducting fieldwork across all communities within each municipality, close to 50% of the communities in both municipalities were randomly selected for the study, stratifying by local language, access to electricity, and population. Naturally, communities with no cell phone coverage, as informed by local authorities, were excluded from the sampling frame .An initial (brief) in-person household listing exercise was conducted in each selected community between November 30 and December 23, 2018. Field staff visited every dwelling in the community, interviewed the household living in it in order to identify those households with targeted individuals (i.e. households with children under two years old and pregnant women), and collected their phone numbers and other basic information. Across all surveyed communities, a total of 2,559 households had at least one child under two years old or one pregnant woman . Of these households, 2,374 (93%) also had access to a cellphone and at least one literate member, which were additional requisites for eligibility. Since the health and nutrition interventions that the targeted individual should receive depend on the calendar established by the official health protocol, individuals from some eligible households did not have an intervention due in the relatively short timeframe of the study’s monitoring period (four months). As a result, only 1,542 of the above households were ultimately eligible for monitoring, which started the last week of January 2019. Refer to The Ministry of Health in Guatemala (MSPAS) produces guidelines defining a series of health and nutrition services ought to be administered at official health centers to pregnant women and children under two years old, at specific months of age (in the case of children) or months of gestation (in the case of pregnant women). Since some health and nutrition services indicated in these guidelines were facing supply constraints and were not being administered at the time of the study, we decided to exclude these, resulting in 13 services for direct monitoring. During the household listing in the selected communities, the age (in months) of children and the months of gestation of pregnant women were collected. Using this information, we were able to determine all upcoming health services that a given targeted individual was due to receive during the monitoring period, resulting in a household-specific calendar of questions to monitor the receipt of these services. Hence, the total number of questions asked varied across each targeted individual. For example, a household with a 2-month-old child at the time of the listing received a total of seven questions during the four months of the effective monitoring period, while a household with a 7-month pregnant woman received three questions in the same period. Questions were administered  one month after the child or pregnant woman was due to receive each health service. As an example, the first dose of the Pentavalent vaccine should be administered at two months of age, so the question was asked when the child turned three months. This one-month window allowed sufficient time for the targeted individual to visit the health center, while at the same controlling for the adequate timing of the service provision according to the MSPAS protocol. The calendar also served to send SMS reminders among the treatment group that was assigned to receive reminders, about a week in advance to the date in which the child or pregnant woman was due to receive each health service.Since the monitoring questions (and reminders) rely on the official guidelines for the timing of services and not on actual appointments made by households with their respective health centers, we also avoid any potential selection bias that may result from differences between households securing and not securing appointments in advance. As the age of the child or month of pregnancy are the only variables determining the interventions to be received and monitored (following the guidelines), and these are ultimately balanced across treatment arms, we do not believe selection bias to be a concern in this regard.While phone calls were made in the main language spoken in the community where the household was located, SMS communication was solely in Spanish for two main reasons. First, local authorities indicated that households tend to use Spanish for reading and writing, even when the local language predominates orally. Second, for compatibility purposes with the automated SMS delivery system, the text messages could not contain certain characters commonly used in the written forms of local Mayan languages. Questions asked over SMS further made explicit that a “YES” or “NO” answer was required , to simplify both the answering process for households and the processing of responses.Since asking whether a child or pregnant woman has received a service they are supposed to receive  poses minimal concerns around confidentiality, we did not explore the feasibility or costs associated with sending encrypted SMS messages. This is an important aspect that should be taken into account when monitoring other type of interventions such as those related to individual-specific health issues, where protecting the confidentiality of participants may be a concern.As noted above, all eligible households were fully informed of the study during the initial, in-person household listing (where phone numbers were collected). A brochure was also provided with the details of the study to all participating households in their local language. Prior to the start of the monitoring period, we further advertised the study through brief interviews in the local radio and television  in order to both remind participating households about the study and encourage them to answer the questions they would be receiving during the upcoming weeks. Similarly, we participated in meetings with local authorities from the communities in both municipalities to communicate the objectives and scope of the study and request their support over the following weeks.The monitoring implementation began roughly one month after the initial household listing with a welcome message to all participating households indicating that they would be receiving questions either by SMS or phone calls (depending on the treatment group) in the upcoming months asking about the health and nutrition services received by the targeted child under two years of age or the pregnant woman. The households in the SMS treatment group also received an initial airtime top-up of 5.5 quetzales (approximately 0.75 US dollars) and an additional SMS informing that these top-ups were provided to help them to answer the questions they would be receiving in the following weeks. The first batch of questions was made on January 27 and the last one on May 26, 2019.SMS-based questions were sent using an automated system for sending and receiving SMSs from a local company. In the system, a processing rule was created to recognize an answer of “YES” or “NO” in all its variants  and to send an automatic response in case the answer did not match this format: “Please answer YES or NO only, we cannot process other responses. Thank you for your participation.” Still, a very small number of responses had to be manually verified and classified as “YES” or “NO.”Eight surveyors (teleoperators) were hired to make the phone calls: three of them speaking Ixil, two Spanish, one Kiche, and two Qeqchi. The proportion of teleoperators in each language was correlated with the language distribution of the monitored households. Regarding the back-end system for phone calls, each surveyor was provided with an automated Excel spreadsheet with a full list of households to be contacted on a particular date, their contact information, and additional information on household members and the listing interview date so contacted households would trust that the call was associated to the study they had accepted to participate in. The spreadsheet included a dedicated solution in Visual Basic that showed the complete list of questions to be asked to a given household on a given date and an entry form to facilitate the recording of answers. The spreadsheets were saved automatically after each call and shared weekly with the researchers.The monitoring occurred on Sundays as it is the day in which the majority of household members are at home. Questions sent via SMS were scheduled to be sent on Sundays at noon and the protocol was to wait until the following Saturday for a response, although 82% of the households that responded to SMS did so the same Sunday or during the following day. In the rare cases where more than one SMS response was received over the week, the last message received was considered as the final response. Phone calls were made on Sundays at different times over the day. When a household could not be reached by phone, no voice-mails were left but additional phone call attempts were made within the same day and the following days . On this regard, it is worth acknowledging that phone calls permitted to make several attempts as opposed to SMS that were only sent once; yet the communication (question) sent through SMS is fully transmitted in the first attempt while the communication through phone calls ultimately depends on the household answering the phone . In any case, similar to SMS, close to 80% of the households that responded the phone calls did so within the same Sunday or over the following day, and one third did so at the first attempt.In some cases, the health services’ protocol from MSPAS indicates the provision of more than one service at a specific time during pregnancy or over the first two years of life. For instance, several vaccine doses should be administered at six months of age, during the same visit. In the case of phone calls, all questions could be asked at the same time once communication with the household was established. An SMS-based mode of communication, however, has the disadvantage of not being able to ask more than one question at a given time: if two questions were sent by SMS on the same day and two answers were received, it would not always be possible to accurately match the answers with the corresponding questions without relying on strong assumptions. This is true when the answers differ or when the number of answers received are less (or more) than the number of questions sent. To solve this issue, SMS questions had to be sent one at a time each week in these situations, which also implied that the SMS monitoring period ended four weeks after the monitoring period using phone calls (as noted in the next Section). This limitation is an important constraint that should be taken into consideration in more complex SMS-based monitoring designs.In order to compare household responses with the official information that the targeted individual had received, administrative records from specific health centers in the municipality of Nebaj were collected after the completion of the monitoring activities. This information was obtained from the Health Management Information System (SIGSA) maintained by MSPAS, which keeps records of several services provided by health centers serving the population of interest. The frequency in which the system is updated varies significantly across locations, reason why we collected this information about one month after finalized the monitoring.We focus on vaccines as the administrative records for vaccines received by children under two years old contain detailed information on the name of the child, date of birth, and the mother’s name (besides the household location and date of service), which permits an accurate one-to-one matching with our dataset. Available administrative records for other services or for pregnant women, for instance, do not include birth date, which difficult a precise matching. This additional exercise allows us to evaluate the veracity of the answers provided using a subsample of monitored children in Nebaj as an example.The data analyses performed in the study are divided into five parts. Given the significant difference in response rates obtained through SMS and phone calls, the analysis for each mode of contact is conducted separately.First, we report overall response rates obtained throughout the duration of the study and disaggregated over time. This includes aggregate tabulations as well as disaggregation by geographic location, predominant language in the community, and type of intervention.Second, we examine the association between sending SMS reminders and receiving health services. We compare the shares of households reporting to have received health services, between communities that received and did not receive reminders.ijR is a dichotomous variable that takes a value of one if household i in location j provided a valid answer and zero otherwise; ijX is a vector of household characteristics such as gender, age, language, and level of education of household head, household size, and distance to the closest health center; ijT represents two indicator variables for the type of intervention monitored (if care intervention during pregnancy and if vaccine intervention); jc is a location fixed effects component  that controls for unobserved factors at the geographic location level that could likely affect households’ propensity to respond; and iju is an idiosyncratic error term. The standard errors in Eq ,jδ+cj+uijwhere thFourth, we evaluate the accuracy of household responses by directly comparing the “YES” and “NO” responses received with the information recorded in the health centers’ administrative data. We work with a subsample of households and focus on vaccines as an example, since this permits for an accurate comparison between the two sources of information, as discussed above.Finally, we discuss the cost-effectiveness of the monitoring tool. We calculate and compare the costs per question sent and per effective response received for both SMS and phone calls.In the case of phone calls, a total of 3,824 questions were asked and 2,900 were answered appropriately, resulting in a global response rate of 75.8%. The larger number of questions asked by phone, compared to SMS, is due to the higher number of households in the communities that were randomly selected to be contacted by phone see . Among tThe contrast between SMS and phone calls is also evident when observing the inter-household variability in response rates. As shown in We further examine whether response rates changed over time. Lastly, Another goal of the study was to evaluate whether sending SMS reminders to households contributed to improving attendance to health centers to receive the corresponding health and nutrition interventions. To test this, we compare the reception rate of services between households in half of the monitored communities that received calendarized SMS reminders and households in the other half of communities that did not receive these. Hence, sending SMS reminders does not seem to be positively associated with a higher reception of health and nutrition interventions. This finding contrasts with other studies –17, whicThis subsection discusses the key identified factors associated with the likelihood or probability of responding based on the multivariate regression analysis defined in Eq . S4 and The quantitative analysis was complemented with a qualitative assessment based on four focus groups we conducted after concluding the monitoring period study. Two communities were selected in Nebaj  and two additional communities in Uspantan. Among participants that received SMS, the main reasons mentioned for not answering questions were a lack of airtime (despite the airtime top-ups provided by the project) and not having been notified about the SMS . Among participants that received phone calls, the few that did not respond also mentioned that they were not notified about the call, as well as other reasons such as a lack of phone access during the day, lack of understanding of the question, or that they had lost their phone. Refer to A final piece to assess the viability of using cell phones to monitor health and nutrition interventions is to evaluate the veracity and accuracy of responses provided directly by households. For this, we examine whether household responses match with the information recorded in the Health Management Information System (SIGSA) maintained by MSPAS, which keeps official records of the different services received by every individual visiting the public health centers. In the case of children under two years old, the administrative records contain detailed information of the different vaccines administered together with the date of service, which can be directly compared with the responses by household. Ultimately, we do not only want to determine whether households respond or not  and their preferred mode of contact, but also whether they respond correctly or not.Lastly, we discuss the overall cost-effectiveness of monitoring interventions through cell phones in our study, which helps put our results in perspective for eventual replications or scaling up of a monitoring system of this nature. It is worth noting that over 75% of the total fieldwork budget was devoted to the initial household listing in the selected communities in order to identify households with targeted individuals and collect their phone numbers and other necessary information. These costs could surely be avoided if household records, including telephone numbers, were collected and maintained by the corresponding local administrative and health authorities, such that households could be contacted without previously visiting them. The remaining share of the budget (less than 25%) was devoted to the monitoring itself.As shown in This study draws several important lessons for monitoring development interventions in rural areas through the use of cell phones.We find a very low overall response rate to questions asked via SMS, at 14.4%, similar to that obtained during the pilot study in Chiquimula, at 12.3%. Since during the household listing we placed special emphasis on verifying the contact phone number provided by the household, the low response rate does not seem to be related to incorrect phone numbers but to a general low propensity to respond to SMS by households.In contrast, the response rate to phone calls was over five times higher compared to SMS, at 75.8%. This points to the enormous potential of using phone calls to monitor development interventions in real time, especially in remote areas with limited accessibility. Phone calls appear to allow for more candid and personalized contact with households, diminishing households’ mistrust relative to, for example, answering SMS from an unknown phone number. Phone calls also permit to ask questions in the respondents’ native language, helping to increase trust and understanding of the information being requested from them. Similarly, phone calls allow to ask several questions in a single call, unlike SMS which cannot handle responses to multiple questions at the same time. In addition, given that incoming phone calls are free in Guatemala, this method eliminates potential liquidity constraints and avoids the need to provide airtime top-ups.The analyses further show that language, level of education, and age of the household head are not critical barriers to obtaining answers through phone calls, while they present major obstacles when obtaining responses via SMS. Moreover, response rates obtained either by SMS or phone calls do not seem to vary according to the geographic location of a household, to whether the monitored individual is a child under two years of age or a pregnant woman, or to the type of health intervention monitored.Furthermore, we find a high level of accuracy in the responses provided by households, with rates of agreement between household responses and administrative records of 84% and 91% for questions asked, respectively, through SMS and phone calls. This indicates, on one hand, that households are generally aware of the specific health services offered by MSPAS and, on the other hand, that they are willing to provide that information without distortion.All in all, we conclude that monitoring development interventions using cell phones is feasible, with phone calls being superior to SMS in terms of household participation, trust, and understanding of the questions asked. In addition, the responses provided are very accurate. The lack of impact found from sending SMS reminders on the reception of health and nutrition services also seems to support the conclusion that communication via SMS is not an effective mode of contact with households.More broadly, the almost identical SMS response rates with those previously obtained in Chiquimula, a department located in the opposite (East) side of the country with very different socioeconomic, cultural, ethnicity, and linguistic characteristics than Quiche, points towards the replicability of the results in multiple rural settings of Guatemala. Moreover, while the department of Quiche presented important challenges for the study such as low levels of education and familiarity with ICTs, multiple languages, or rugged geography and poor network connectivity, the study shows that a monitoring system based on direct phone calls to households is both feasible and effective. In this regard, we would expect our study findings to be replicable in other rural contexts around Latin America and arguably other regions around the world. Nevertheless, we recognize that assessing external validity is ultimately an empirical matter that should be further examined in future studies.Finally, while setting up a monitoring system with calendarized phone calls requires establishing a specialized (part-time) call center, with enough teleoperators who speak all the relevant languages of the population of interest, the costs of implementing such center are lower than using a specialized automatic platform to send and record answers by SMS (in addition to providing households with airtime top-ups to respond to the SMS). If we additionally take into account the high response rate to phone calls, a monitoring system of this nature can be a low-cost, effective tool to collect timely and reliable information for program implementors, donors, and policymakers. More generally, considering the current lockdown measures and suspension of in-person field activities due to the COVID-19 crisis, phone calls can be a valuable instrument for monitoring purposes and to implement brief surveys.S1 Fig(TIF)Click here for additional data file.S2 Fig(TIF)Click here for additional data file.S3 Fig(TIF)Click here for additional data file.S4 FigThe vertical lines correspond to the 95% confidence bands.(TIF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 TableThe table reports the corresponding averages and standard deviations in parentheses. The p-value results from the orthogonality test between the two household groups; a value larger than 0.05 indicates that the difference in each variable between the two groups is not statistically different at a 95% confidence level.(DOCX)Click here for additional data file.S4 Table*** p<0.01, ** p<0.05, * p<0.1. Standard errors reported in parentheses clustered by community. Estimates include an indicator variable that takes the value of one when a household head did not report an education level or a household did not report distance to the health center, and zero otherwise. For these cases, we imputed the median distance at the community level. Model estimated by ordinary least squares.(DOCX)Click here for additional data file.S5 TableNote: *** p<0.01, ** p<0.05, * p<0.1. Standard errors reported in parentheses clustered by community. Estimates include an indicator variable that takes the value of one when a household head did not report an education level or a household did not report distance to the health center, and zero otherwise. For these cases, we imputed the median distance at the community level. Model estimated by ordinary least squares.(DOCX)Click here for additional data file.S6 TableResponses from 47 women that participated in the focus groups conducted.(DOCX)Click here for additional data file.S1 Appendix(DOCX)Click here for additional data file.S2 Appendix(DOCX)Click here for additional data file.S1 Data(XLS)Click here for additional data file.S1 File(PDF)Click here for additional data file.


Vesicoureteral Reflux (VUR) is characterized by a retrograde flow of urine from the bladder into the ureters and kidneys. It is one of the most common urinary tract anomalies and the major cause of urinary tract infection (UTI) in the first years of life. If not properly diagnosed and treated can lead to recurrent UTI, renal scar and, in severe cases, to end stage renal disease. Despite recent advances in scientific and technological knowledge, evaluation and treatment of VUR is still controversial and there is still considerable heterogeneity in evaluation methods and therapeutic approaches. The aim of the present consensus is to give a practical orientation on how to evaluate and treat VUR.The board of Pediatric Urology of the Brazilian Society of Urology joined a group of experts and reviewed all important issues on Vesicoureteral Reflux evaluation and treatment and elaborated a draft of the document. On November 2017 the panel met to review, discuss and write a consensus document.Vesicoureteral Reflux is a common and challenging problem in children. Children presenting with Vesicoureteral Reflux require careful evaluation and treatment to avoid future urinary tract infections and kidney scars. The panel addressed recommendations on up to date choice of diagnosis evaluation and therapies. Vesicoureteral reflux (VUR) is defined as the backflow of urine into the ureter and kidney. It is one of the most common urological anomalies in children with an incidence of 0.5% to 3% in the general pediatric population   , 2 . ThThe backflow of urine into the kidney predisposes bacteria to ascend causing pyelonephritis. The immunologic and inflammatory response to the infection may lead to renal lesions and formation of renal scars   , 7 .VUR is one of the most important diseases of childhood and, when not properly treated, presents high morbidity and can lead to significant renal damage and, if severe, consequent hypertension and chronic renal failure. Reflux nephropathy is responsible for up to 25% of cases of end stage renal disease   .The two most common forms of VUR presentation are urinary tract infection (UTI) and prenatal hydronephrosis. With the advent of antenatal ultrasound (US) more reflux cases are being diagnosed on the neonatal period. Of all cases of prenatal hydronephrosis, 15 to 21% are caused by VUR   , 10 . OVUR is classified according the degree of ureteral, renal pelvis and calix dilation and varies according to severity from grade I to V     11 ). .11 ). TInvestigation and management of VUR management is still controversial. Voiding Cystourethrography (VCUG) is considered the gold standard for diagnosing and evaluating VUR grade. Catheterization for VCUG can be traumatic for both the child and family   . Not alIn the same way, the role of antibiotic prophylaxis and surgical treatment  have also been questioned and there is no clear indication of which the best treatment modality would be, especially in VUR of low or intermediate grades.This Brazilian Guideline on evaluation and treatment of VUR has no intention to answer all these questions but to guide urologists, pediatricians, and pediatric nephrologists on the most recent aspects related to the management of children with vesicoureteral reflux.The board of Pediatric Urology of the Brazilian Society of Urology, noticing the need of a Brazilian guideline on vesicoureteral reflux, joined a group of experts to review the important issues on VUR and elaborated a consensus document. Eight renewed pediatric urologist with known experience in dealing with urinary tract infections and vesicoureteral reflux were invited to participate in the elaboration of a document with the scope of the guiding urologists, pediatricians, nephrologists and others that deal with children with vesicoureteral reflux on the most important and up to date aspects of the evaluation and treatment of those children.All panel members were instructed to perform a literature search on MEDLINE, EMBASE and COCHRANE LIBRARY databases as well as a review of the base of practical guidelines database for the last 20 years using the term “vesicoureteral reflux”. Papers were selected according to their level of evidence, giving more importance to meta-analysis, systematic reviews, and randomized controlled trials. Cohort and series of patients were used to add information. Review papers and guidelines were used as orientation for which topics and aspects would be included.After the papers were selected, each member of the group was designated one topic to review and write an orientation document based on the recommended literature.On November 2017, all members joined together during 2 days to review and discuss the previous written documents of each topic and prepare the consensus document. Further discussions, corrections, and revisions were carried out digitally, until all members of the panel have approved this final document. A paragraph containing the panels opinion (“consensus”) was added at the end of each section to guide the reader about the information provided and the most common practice on each specific subject.As in all fields of medicine, a careful clinical history is very important for the diagnosis. Aspects related to the presence of prenatal hydronephrosis, past episodes of febrile and non-febrile UTI should be investigated. Understanding voiding and bowel habits are important since lower urinary tract dysfunction (LUTD) and constipation are often associated with UTI and VUR   - 21 . VIn all toilet trained children, a very meticulous clinical history of their voiding symptoms, such as increased voiding frequency, incontinence, urinary urgency, holding maneuvers, and also, constipation should be taken. Physical examination should include assessment of weight, height, and blood pressure, palpation of the abdomen looking for masses and globus vesicalis, presence of feces in the bowel, and evaluation of the genitalia. Examination of the back in search for skin markers suggesting occult spinal dysraphism is important since VUR is present in up to 25% of children with spinal dysraphism   .Clinical history should be periodically reevaluated during follow-up, since symptoms may change. LUTD and constipation should also be frequently assessed during the course of treatment.The final diagnosis of VUR will be obtained only with an imaging test. The imaging test for defining VUR diagnosis should be ideally radiation free, with no need for urethral catheterization or sedation, presenting high accuracy and anatomical detailing and with low cost. Unfortunately, none of the currently available imaging tests (VCUG or direct cystocinthigraphy) fills all or most parameters named before.Serum creatinine dosage is indicated in cases of bilateral high grade VUR and/or presence of bilateral renal scars, being a parameter to estimate the rate of glomerular filtration and as a baseline for future comparisons.Urine analysis, including proteinuria, bacteriuria, and urine culture are recommended for the diagnosis of VUR and subsequently for suspected UTI. The recommended method for urine collection in children that are not yet toilet-trained is via clean urethral catheterization to avoid contamination   , 26 .We do not recommend periodic urine analysis and urine culture in asymptomatic children. Investigation of UTI in cases of fever of undetermined origin in patients with VUR must always be performed.Ultrasound is not accurate in predicting the presence of VUR and should not be used for the diagnosis of VUR   - 29 .Ultrasonography of the urinary tract is recommended to monitor renal development, as well as assess the occurrence or worsening of hydronephrosis, and presence of post voided residue urine. It is important to observe bladder filling during the exam, as this may be correlated with the degree of renal dilation. Ultrasound examinations should be performed at least every 6 months.The goals of DMSA scan are to look for the appearance or progression of renal scars and monitoring renal function   , 31 . TThe “top-down” approach, which means that the evaluation starts from the kidney by ordering the DMSA scan during the acute phase of the UTI was proposed with the aim to avoid unnecessary VCUG and has a sensitivity of up to 95%   . In thiOn the contrary, the “bottom-down” approach    advicesIn a less invasive way of evaluating children with UTI DMSA, scan would be ordered only in cases of febrile UTI, high grade VUR (IV and V), and changes on ultrasound suggestive of renal lesions.As for periodicity, DMSA scans should be repeated only after presentation of new episodes of febrile UTI.Voiding Cystourethrography (VCUG) uses iodine as a contrast medium and allows the classification of VUR as well as evaluation of bladder and urethral anatomy. Because reflux may be an intermittent phenomenon, the test should be performed with fluoroscopic monitoring and with more than one bladder filling cycle, not to exceed three cycles.It is recommended that it should be done at earliest convenience following UTI treatment   , confirThe main advantage of VCUG over Direct Isotopic Radionuclide Cystography is related to the anatomical detail. In addition, the current VUR grading system is based on VCUG. Therefore, VCUG remains the gold standard diagnostic test and initial evaluation of VUR.Direct Isotope Radionuclide Cystography can replace VCUG for the diagnosis or follow-up of patients with VUR. In this method, a radio-isotopic tracer  is infused in the bladder after urethral catheterization and images are obtained during bladder filling and emptying.Although radio-isotopic method is believed to have less radiation exposure   , a receOther methods have been developed in an attempt to reduce the morbidity of traditional exams (VCUG and DIRC) in the diagnosis of VUR. Ultrasonographic Cystography has been shown to be very accurate in diagnosing VUR   , 40  alThe panel believes that a careful and meticulous clinical history considering all aspects discussed above and with special attention to LUTD should be obtained prior to any imaging test. All children should be evaluated with a renal ultrasound with the evaluation of post-voided residual urine. Renal Scans with DMSA should be reserved for those with history of febrile UTI, VUR grade IV or V and ultrasound suggesting renal lesions. VCUG should be the imaging test of choice for the diagnosis of VUR. DIRC should only be indicated on the follow-up, especially after surgical treatment.The indication for VCUG may vary according to the clinical presentation of the patient and some protocols have been proposed for this purpose.The indication of a VCUG in the evaluation of a child presenting UTI is still controversial. Children presenting febrile recurrent ITU and/or in cases where alterations of the urinary tract are found in the ultrasonography should be evaluated with a VCUG   .Despite that requesting a VCUG after the first episode of febrile UTI in infants is still questioned by some authors, we believe that it could be done in those cases   .On the other hand, in older children with recurrent afebrile UTI, VCUG is exceptionally indicated, since the main etiology of UTI in this group of patient is LUTD   .VCUG is recommended in newborns with postnatal ultrasound findings of bilateral grade II to IV and unilateral grade III to IV hydronephrosis-Society of Fetal Urology-SFU   , 44 , sFor grade II hydronephrosis its indication is controversial, but there may be benefits. In case of degree I hydronephrosis its routine indication may be dispensable.Routine investigation of asymptomatic siblings and/or children of patients with VUR is controversial. The lack of randomized clinical trials to detect VUR in these patients makes it difficult to routinely recommend it. Parents of children with VUR must be informed that there is a high prevalence of reflux in siblings and offspring, and if the decision is made to investigate, the initial examination should be ultrasonography, with VCUG reserved only for cases of significant changes on ultrasound or after UTI episodes   , 46 .Although the indications for investigation of VUR in children presenting UTI are controversial, the panel agrees that is mandatory that all children with febrile UTI and changes in the ultrasound, and infants with UTI, regardless of changes in US, must be investigated, and encourages investigation of children with well documented UTI, regardless of changes in US. Older children should be carefully evaluated for LUTD. Children presenting with prenatal hydronephrosis should only be routinely investigated if they present high-grade hydronephrosis (grades III and IV) or if ureteral dilation. Investigation of siblings and offspring of patients with VUR should be discussed with the family and, if investigation is the option, it should start with US.The use of low-dose antibiotics to prevent UTI in children with VUR is based on the observation that VUR has a high spontaneous resolution rate in the first 4 to 5 years of life    - 50  anRecently, a large multicenter, randomized study including 607 children with VUR diagnosed after the first or second UTI and with a 2-year clinical follow-up demonstrated that CAP is associated with a significant reduction in the risk of UTI episodes but not new scars (Grade of Recommendation A)   . RecentThe duration of CAP is still controversial. One option would be to perform VCUG periodically  and, if there is resolution of the reflux, stop the CAP. Another option is stop CAP in toilet trained children with no LUTD. In children who, even when using CAP, present new episodes of UTI, surgical treatment should be an option   .Continuous antibiotic prophylaxis, when instituted, should be adequate for the child’s age group and the antimicrobial susceptibility pattern of the population in the area the child lives.The drug of choice should be well tolerated, with low risks and side effects and be affordable, considering ongoing treatment. The dose to be administered is between 25 to 50% of the therapeutic dose, which should be adjusted periodically, according to the child’s weight gain, which is more significant in the first year of life. The drug of choice in infants, in the first 6 months of life, by the availability and drug safety, should be Cephalexin or Amoxicillin. Use of Sulfamethoxazole and Nitrofurantoin are not indicated before 2 months of age. For children older than 6 months of age, the options would be Cephalexin, Amoxicillin, Sulfamethoxazole/Trimethoprim, Nitrofurantoin or Nalidixic Acid.Based on the studies discussed above, the recommendation of this panel is that CAP should be indicated in all infants and children who have not yet completed sphincter training and who present VUR grade III or higher. However, those with VUR grade I and II also appear to benefit from CAP and the decision should be made after discussing with the family.The management of VUR aims to prevent the onset of new episodes of UTI and loss of renal function. Clinical treatment consists of continuous administration of low-dose antibiotics to maintain sterile urine and thereby prevent pyelonephritis and formation of renal scars. The basis of clinical treatment is the expectation of spontaneous resolution, since VUR tends to decrease in grade or completely resolve with time   , 50 . TGrade of VUR: The higher the grade of the VUR, the lower the chances of spontaneous resolution. Refluxes of dilated degrees (IV and V) present a probability of spontaneous resolution of 5 to 20%, while in VUR grades I and II resolution occurs in more than 80%  presents a lower probability of spontaneous resolution compared to unilateral VUR : Non-absorbable. Due to the greater hardness of the material, it is necessary to use an injection gun   - 88 .Dextranomer/Hyaluronic Acid (Deflux®): Advantage of being easy to inject and with fewer complications   . As a dPolyalcohol/Polyacrylate (Vantris®): Not to be absorbed and easy to inject. As a disadvantage, it causes a higher inflammatory process and, therefore, has a higher risk for obstruction   - 93 .Pyrolytic Carbon (Durasphere®): Its application is difficult and there are few studies showing its effectiveness   .Subureteral injection (STING): In this technique, the injection site is about 2-3mm below the ureter orifice (at 6 o’clock) and the needle is deepened by 4-5mm   , 96 .Hydrodistension Injection Technique (HIT): In this technique, the flow of endoscopic irrigation is positioned immediately in front of the ureteral meatus. The substance is injected approximately 5mm into the ureter. More than one injection is possible with this technique (Double HIT)   , 98 .The higher the VUR grade the lower the success rate. Other factors related to lower success rate are LUTD, surgeon’s experience, and previous injection   - 101 .Patients should perform ultrasonography after surgery, preferably between one and three months   , 102 .Performing VCUG after the procedure is optional, and should be indicated in case of relapse of febrile UTI.This panel recommends the endoscopic treatment of VUR as the first surgical treatment option, except for Grade V VUR with significant ureteral dilatation.The panel also recommends that after a second unsuccessful endoscopic injection, the possibility of treatment with open surgery should be considered. There is insufficient data in the literature to evaluate the results of re-application of Polyalcohol/Polyacrylate. Therefore, according to this panel, open surgery should be considered after failure to a first injection with this material.If Dextranomer/Hyaluronic Acid is the bulking agent of choice, consider injecting higher volumes and use of HIT technique. If Polyalcohol/Polyacrylate is the bulking agent chosen, it is advised to use lower volumes and not use the HIT technique due to the higher risk of obstruction.This panel recommends performing at least one annual ultrasonography, as late obstructions have been reported, especially after Polyalcohol/Polyacrylate injection.Ureteral reimplantation is the most effective approach to prevent new episodes of febrile UTI, especially in high grade VUR or after unsuccessful endoscopic injection. All techniques have high success rates (>95%)   , 75 .Complications include the possibility of obstruction (2%) and contralateral reflux (9%).The principle of all ureteral reimplantation techniques is to create a longer submucosal tunnel, four to five times the diameter of the ureter, in an attempt to reproduce the physiological anti-reflux mechanism of compressing the ureter as intra-vesical pressure increases with filling and urination   .Intra and extra-vesical procedures as well as combined techniques have been described. The choice of technique depends on the degree of dilation of the ureter, whether the reflux is unilateral or bilateral, the presence of other obstructions, and the preference of the surgeon.Intra-Vesical: Cohen and Glenn-Anderson  should be treated with ureteral reimplantation, either with open of laparoscopic/robotic techniques depending on the experience of the surgeon and the availability of the technology. In unilateral cases, extra-vesical approach should be considered while in bilateral cases, intra-vesical technique (Cohen) would be preferable.There is no consensus regarding postoperative follow-up both in endoscopic treatment and in open, laparoscopic or robotic surgery. As the success rate of the procedures is high, it is not recommended, in general, to perform control VCUG in all patients, which should be indicated in patients with new episodes of febrile UTI and, possibly, in patients with high grade VUR treated with endoscopic procedure, where the success rate is lower.Ultrasonography is performed between 1 and 3 months after the surgical procedure and is performed at regular intervals after endoscopic treatment because of the risk of late obstruction.It is the panel’s opinion that a kidney and bladder ultrasound should be done after the first month of surgery to check for signs of obstruction. VCUG is indicated only in case of breakthrough UTI or after endoscopic treatment of high grade VUR.


Antimicrobial resistance is one of the greatest global healthcare challenges of our time. It is an anthropogenically amplified natural response by bacteria and fungi to the selective pressure provided by extensive and excessive use of antimicrobials. The scale of use of antimicrobial compounds is truly astonishing and underpins their position as cornerstones of both developing and developed national-scale healthcare and food production systems.While the importance of antimicrobials to society is in no doubt, companies involved in research and development of antimicrobials struggle to make their research effort viable from the perspective of economic return. There has been an exodus of pharmaceutical companies from the antimicrobial development field, including pharmaceutical giants such as, AstraZeneca (UK), Novartis (Switzerland) and Sanofi (France) and the recent bankruptcy of smaller companies , despite these having successfully navigated complex regulatory hurdles and bringing an antibiotic to market. The reasons for these divestitures and insolvencies are due to the lack of returns associated with the current for-profit economic model of financial reimbursement for bringing a new antimicrobial product to market .While it is encouraging to see an increase in the number of compounds in pre-clinical testing, which has been catalysed by recent increased funding, there is still a recognised lack of compounds entering the pipeline . Due to In addition to the development of new antimicrobials, part of the recommended response to antimicrobial resistance is increased public awareness campaigns. A multitude of successful public-engagement projects have emerged over the last few years , in diffIn order to expand initial antimicrobial discovery activity beyond soil microbes and to circumvent the absence of funding and create a dynamic, long-term, public-engagement activity, the citizen science project ‘Swab and Send’ was launched in early 2015. It was designed to enable individuals to decide where and what to sample in order to try and find bacteria or fungi, which can produce antimicrobial products against a range of bacterial and fungal indicator strains.Penicillium notatum, the original producer of penicillin isolated by Alexander Fleming, was replaced with a strain of Penicillium chrysogenum producing many times more penicillin. This P. chrysogenum was isolated from a cantaloupe as part of a nationwide citizen science effort aimed at finding more efficient penicillin producers [’ based at the University of Oklahoma (USA) [’ project run by the Microbiology Society in the UK [Citizen science is historically rooted in antimicrobial discovery. Indeed, the first strain of roducers ,6. Therema (USA) , ‘Drugs ma (USA)  and the n the UK , which wn the UK , a US baSwab and Send relies on social media; primarily using Facebook to report results back to participants and Twitter (#swabandsend) to reach potential participants including members of the public, school, colleges and other organisations. As external research funding is rare for this initial discovery activity due to the high likelihood of failure, costs are covered by a small pledge from participants using an online form. Swabs are posted with instructions detailing what to consider when deciding what to sample. While imagination is encouraged in terms of what is sampled, we do say that animals and humans should not be swabbed for safety reasons, we do however regularly receive samples from humans (particularly school children) and many animals, with an inexplicable over-representation of cats.Once we receive the samples back in the laboratory, they are streaked onto agar plates and incubated for 4–7 days at room temperature. Each individual morphologically distinct colony is then picked, using a sterile pipette tip, into a microtiter plate well containing growth medium and incubated at room temperature overnight. Following the phenotypic assays described below, the microtiter plates are stored at -80°C, following the addition of glycerol, for future assays.Micrococcus luteus, Staphylococcus aureus, Escherichia coli, Candida albicans or Candida auris) and allowing to dry. The cultures from the microtiter plates are replica plated onto these pre-inoculated agar plates, which are incubated at room temperature for 2–3 days checking for growth each day. We analyse the assay plates for zones of inhibition around the colonies originating from the swabs and all the agar plates are photographed along with a template sheet detailing which sample is positioned where within the microtiter plate. These are uploaded onto the dedicated Facebook project webpage [Klebsiella grimontii strain isolated from a reusable water bottle [The phenotypic assays are carried out by inoculating agar plates with an overnight culture of our indicator strains  and sigE. coli, C. albicans and C. auris are taken forward to cell free assays to determine if we can follow the antimicrobial activity of the secreted molecules. The hit isolates are also genome sequenced for de-replication purposes as we want to avoid working on a compound already reported and candidate molecules can often be inferred from genomic data where we can identify biosynthetic gene clusters.Currently, hits against Feedback on the project is overwhelmingly positive and is left via the website and via personal correspondence to the author. It is clearly reaching a large number of individuals evidenced by analysis of over 2000 swabs and the testing of over 4500 isolates against our indicator strains. We have received swabs from numerous members of the public, more than 20 schools, colleges and universities and have taken part in multiple events including the Microbiology Society 75th Anniversary, the Surgeon X Launch Party, the TEDxLSTM talks, the Big Bang Fair, Thought Bubble Festival and New Scientist Live to name but a few. Coverage of the project has appeared in various National Newspapers in the UK including the Times, The Guardian and The Telegraph plus The Atlantic in the US and various other publications and radio broadcasts throughout the world. In addition, we have worked with the BBC in the UK on Trust Me I’m a Doctor and more recently on The Truth About Antibiotics. The reach of the project from the various media outlets and the social media platforms is substantial with some social media posts reaching in excess of 1 million views and upwards of 50,000 interactions.Candida species, 60 against E. coli, 100 against methicillin-resistant Staphylococcus aureus and in excess of 500 against M. luteus. Excitingly we have isolates that can kill or inhibit the growth of different combinations of the indicator strains, including a small number active against only one of the two Candida species. This is likely to be advantageous when we are at a stage to determine the target of the compound(s) produced by these isolates.Scientifically we are also finding interesting bacterial isolates that are being taken forward into traditional scientific investigations within the Centre for Drugs and Diagnostics at Liverpool School of Tropical Medicine (UK). We currently have approximately 50 hits against each of the In addition to the continuing public-engagement activities and the ongoing investigations of antimicrobial producing strains, the project has also resulted in a valuable physical resource. Along with what we have already screened, we have over 10,000 isolates stored, assay-ready, as glycerol stocks in microtiter plates, awaiting antimicrobial assays. The entire isolate library, which is possibly one of the most random microbial isolate libraries in the world, is available for screening should a project with a suitable assay present itself.Looking at the future of antimicrobial discovery, which is constantly stated as being an international priority, it is not difficult to envisage nationally funded antimicrobial screening programmes of samples sent in by the public, which could be used to bolster national and international efforts to refill the antimicrobial pipeline. The major factors limiting success of screening projects is scale and capacity, which are dependent on resources, both financial and expertise. We would be wise to protect the latter by providing the former.


Gnomes. The history shows that groups such as the Gnomes offer a number of important benefits not available in larger societies and nurturing such groups advances science and medicine in meaningful ways. The success of the Gnomes’ approach provides a road map for future small scientific groups.Professional societies play a major role in medicine and science. The societies tend to be large with well-developed administrative structures. An additional model, however, is based on small groups of experts who meet regularly in an egalitarian model in order to discuss disease-specific scientific and medical problems. In order to illustrate the effectiveness of this model, the history and practices are examined of a long-standing successful example, the International Liver Pathology Group, better known as the The online version of this article (10.1007/s00428-020-02879-5) contains supplementary material, which is available to authorized users. Professional societies play a major role in shaping concepts, prioritizing academic pursuits, and providing expert guidance for clinical management challenges in patient care. Professional societies in most settings tend to be large in order to maximize impact. They have permanent bureaucratic structures to help them operate consistently and effectively, including official bylaws and standard operating procedures that outline committee structure and committee interactions, with a President and Executive Committee, and frequently a professional manager overseeing the entire operation.An additional model, however, is based on small groups of experts who meet regularly in an egalitarian model without formal structure in order to discuss disease-specific scientific and medical problems. Of course, this model is not intended to replace or compete with the roles of traditional professional societies, but this model is nimble and flexible and can have a great impact on medicine and science. In order to illustrate this model, the history of a notable example is studied: the International Liver Pathology Group that in 2018 celebrated its 50th anniversary.Gnomes, emerged spontaneously in 1967 when a group of expert hepatologists and liver pathologists met to take on one of the most pressing problems of the day—how should chronic hepatitis be conceptualized, and what terms should be used to capture the various injury patterns seen on liver biopsy? This problem emerged because of the rapid spread during the 1950s and 1960s of the then new technique of using needle biopsies for the diagnosis and management of patients with liver disease. It was clear to pathologists and hepatologists that there were different patterns of hepatic injury, but the different patterns and their significance were confusing, at one point leading to at least 40 different terms in use for chronic hepatitis in the medical literature [The International Liver Pathology Group, better known as the This issue was tackled in 1966 by the leadership of the newly formed European Association for the Study of the Liver (EASL) at the first annual meeting in Marburg, Germany. The EASL President, Gustav-Adolf Martini, and the Secretary, Jan De Groote , recognized the need for consensus on terminology for hepatitis injury patterns, so that uniform terminology would be used in the literature and permit fuller and more rapid progress in understanding inflammation of the liver . To addrde facto scribe and the meeting summaries formed the basis for the group’s first paper [The Lancet in the fall of 1968. The classification system proposed in the paper attempted to identify patterns of hepatitis that were more likely to progress to cirrhosis (chronic aggressive hepatitis) versus those that were thought to be more indolent (chronic persistent hepatitis). This classification system built upon the earlier work of Valeer Desmet [The Zürich meeting was hosted by Martin Schmid, another founding member of the Gnomes, and was sponsored in part by Hoffman-La Roche & Company . The papst paper . The papr Desmet , which iFollowing the Zürich meeting, this consensus paper was presented at the 1968 World Congress of Gastroenterology in Prague and subsequently at Karlovy Vary, Czech Republic, for the 1968 meeting of the International Association for the Study of the Liver (IASL) , 4. The Gnomes of Zürich referred to a popular notion that a small secretive group of elect bankers in Zürich had an undue influence on the world’s financial systems. When the term Gnomes was first used by Sheila Sherlock, it was thus intended to be disparaging. The term, however, was gradually adopted by the group, with a bit of humor and as a badge of honor, being more convenient than the official name European Liver Pathology Group (1968–1978) or the more expansive name International Liver Pathology Group, which was adopted in 1979 when Kamal Ishak joined the group as the first non-European. In publications, the authorship byline was often listed simply as “International Group.” While the more formal name International Liver Pathology Group is still occasionally used, by and large members refer to the group as the Gnomes. Other key events in the history of the Gnomes are listed in Table The term gy Group 968–1978 emeriti” Gnomes are always welcome to continue attending the meeting and otherwise fully participate.There were nine founding members of the Gnomes Table . Three oTo date, there have been 36 Gnomes. All members were European until Kamal Ishak was inducted into membership in 1979 Table . Technich-index of 54 (range 27–77). At the time of the 2018 meeting, their individual publications had been referenced in the peer-reviewed literature a total of 202, 550 times, with an average of 14, 468 citations per member . In addition, at the time of the 50th year anniversary meeting, they were editors or sole authors on thirteen books on liver pathology, including the seminal MacSween’s Pathology of the Liver and the volume on Liver Tumors published by the AFIP [When new members are needed, names of candidates are proposed by any active member and discussed by the entire group, with a final decision put to a vote. Criteria for membership are equally weighted towards scientific interest, diagnostic or clinical expertise, collegiality, and friendship . Nonethethe AFIP –21. FinaOver the years, the Gnomes have become aware of the critical shortage of pathologists in developing countries. The 2012 meeting, hosted by Franesco Callea, was held in Tanzania to support his ongoing efforts to provide pathology training at the Catholic University of Health and Allied Sciences – Bugando, Mwanza .The group originally considered becoming a subcommittee of the EASL, but the members felt there were significant benefits to remaining an independent organization . The groOne of the key missions of the Gnomes is to publish position/nomenclature/review articles to help advance the scientific understanding of liver disease . To thisFifty years is a long time for a small group to survive, let alone thrive—why has the Gnomes been successful and lasted so long? Peter Scheuer emphasized the deep satisfaction of sharing cases with other skilled pathologists, scientists, and clinicians who share a passion for liver disease , as did The notion of group fit comes through as a key element important to the health of the Gnomes , 4. ThisA third key element noted by Valeer Desmet is the ability to organize the group’s efforts on a regular basis into meaningful contributions to the scientific literature . All of Finally, the seamless integration of the Gnome partners and other family members into the social activities of the evenings and weekends brings to the Gnomes a true sense of community Fig. .. MemberLeonardo Bianchi emphasized the importance of pre-meeting circulated slides and pre-meeting submission of diagnoses as a key element of the Gnomes . Based oIn addition, the careful examination of the H&E-stained slide at these meetings has led to the detection and interpretation of previously undescribed structural and cellular alterations. The Gnomes not only fully embrace modern approaches such as molecular pathology, but also understand the continued value of careful morphological studies. Examples of observations made at Gnomes meetings and subsequently described in follow-up studies include the strong association of calcification within alpha-1-antitrypsin globules with the Mmalton variant , the visThe Gnomes’ slide sets are also very important as tools for educational training, including places or countries where H&E is the only available stain. In the last few years, some of the Gnomes have submitted scanned digital slides instead of glass slides, which also serve as an important educational tool, though the relative advantages and shortcomings of their use are still being explored.At the end of the meeting, there also are opportunities for members to present their personal ongoing research. The opportunity to fully and openly discuss early ideas and data has been important in the process of refining many new ideas. There is a well-respected honor code that allows presentation of these initial ideas and early study results, without concern for other members absconding with them. These scientific topics incorporate and extend classical morphology using experimental models, molecular techniques, and biochemical methods, in order to better understand the basic principles of the disease and its morphological patterns. As one example, early work on the keratin nature of Mallory-Denk bodies was presented by Helmut Denk to the Gnomes, leading to vigorous and fruitful discussion by the group.Elves, assisted by Peter Scheuer, one of the founding Gnomes members. Their formal name “The International Liver Pathology Study Group” is easily confused with the formal name of the Gnomes , so both groups generally use their more informal but distinctive names. The Elves have enjoyed great success and their history and accomplishments were recently reviewed [The core elements of the Gnomes model have been replicated by another group of liver pathologists, founded in 1990 and called the reviewed .The Gnomes have consistently contributed to liver pathology for 50 years, but the future depends on the efforts of current members to keep it relevant, healthy, and productive. This depends on wise choices when selecting new members and on a rigorous and vigorous pursuit of the fundamental goal of the Gnomes: to improve the understanding of liver disease by tackling important issues in patterns of liver disease and in terminology.For the first 50 years, the Gnomes focused their efforts on the histomorphologic patterns of disease. These activities remain important but now have to be more fully interwoven with the advances in the treatments for liver disease and improvements in non-invasive methods for diagnosing liver disease, assessing disease activity, assessing fibrosis, and integrating molecular findings into patient care. Starting about 10 years ago, the changes in treatment of liver disease have been rapid and sometimes stunning, with hepatitis C being a good example, in which rapid changes in the treatment and in non-invasive methods of assessing fibrosis have eliminated most of the clinical need for liver biopsy. These improvements in patient care are celebrated by all, especially Gnomes members.Antipathy towards the value of liver pathology, however, is spreading among some clinicians, who express doubts about its usefulness in diagnosing and managing liver disease. The reasons for this are complex, but in part include the reduced exposure and understanding of liver pathology by newly trained physicians, who often receive considerably less training on normal histology and histopathology during medical school than formerly. In addition, there is a natural revision of diagnostic and treatment algorithms as new technology improves patient care. Refining the best fit for invasive and non-invasive methods in patient care takes time. Nonetheless, in all areas in which liver pathology can improve patient care, the Gnomes are committed to vigorously advancing the science of liver pathology interpretation.The Gnomes experience indicates that small, agile professional groups can play an important role in medicine. These, and others like it, offer a number of specific benefits not available in larger specialty societies. We believe that nurturing such groups advances science and medicine in important, meaningful ways. The documentation of the Gnomes approach can provide a road map for the formation of future groups with a specific scientific focus.ESM 1(DOCX 20 kb)


Poppy shells contain opioids. It is a popular, but illegal spice in China. If these shells are added to food, urine morphine test of the patients involved in methadone maintenance treatment (MMT) can turn out positive. A 44-year-old male patient, who had been receiving MMT for 12 years with an extremely good treatment adherence, presented with positive urine morphine test in routine clinical compliance monitoring. However, the patient denied the use of any opioids recently. Coincidently, all of his four family members (none with a history of heroin abuse) showed positive results in urine morphine test. Considering that all these people ate a hot pot together a day before the test added to the speculation that the positive result could be due to the addition of poppy shell to the hot pot. Based on our results, we propose that this unusual phenomenon is worthy of clinical attention when managing patients at MMT clinics. Opioid abuse is a global public health concern . In ChinHowever, this management model has some limitations, such as the continued use of heroin by the patient. To avoid this non-adherence behavior, Chinese patients under MMT are required to receive urine morphine test once a month. A positive urine morphine test generally indicates the use of heroin by the patient in a recent few days, suggesting a failure to adhere to the MMT. Furthermore, because of the interaction between heroin and methadone, the adjunctive use of heroin may lead to fatal methadone overdose.This report presents the case of a Chinese MMT patient who was found to be positive in the urine morphine test although he did not have a history of heroin use since a few days before the test.The medication history and medical events were summarized in The compliance of the patient to MMT was extremely good. However, on October 22, 2019, he was tested and found positive for the urine morphine test. Mr. Zhang was very surprised about the result, and the patient denied using any opioids. On that day, the patient's Clinical Opiate Withdrawal Scale (COWS) score was 2 and the visual analogue scale (VAS) score was 0. Moreover, our team reviewed the patient's outpatient medical records in the past year. As per the record, in the past year, the common health indicators of the patient in the outpatient department were generally normal, such as electrocardiogram (ECG), blood routine, liver function, renal function, and blood glucose; the patient visited our clinic nearly every day, and the result of his urine morphine test was always negative.After detailed inquiry, this patient recalled that he and his family had eaten hot pot at a restaurant a day before the positive testing. People who ate with him included his parents, wife, and son. After providing informed consent, we obtained the blood samples of the patients' four family members and conducted a urine morphine test on the samples on the same day. All the results obtained were positive. On October 23, 2019, the urine test was performed again for the entire family, and all the results came negative. Later, after repeated inquiries by the patient, the hot pot owner privately admitted that poppy shells were added to the hot pot soup served to them. Therefore, we speculated that the positive test results of the entire case family were a result of consumption of poppy shells-added hot pot. Following a 3-month outpatient follow-up, the patient's urine test results came negative. Throughout the follow-up, we continued to encourage and psychologically support the patient, making him believe that he is a model of successful detoxification who may hopefully exchange his experience with other needy people. Fortunately, all the patients and their families were very happy to know of the successful treatment outcome.Hot pot is one of the most popular Chinese foods. As a Chinese traditional cooking skill, poppy shell or its powder is occasionally added to hot pot, based on an old rumor that poppy shells make food more delicious. Furthermore, in this way, even in restraints, the dining experience of diners is improved. As a result, hotpot restaurants attract increased customer traffic. Generally speaking, diners believed that eating food containing poppy shells produce a certain level of euphoria experience as a result of the addition of a small amount of opioid ingredients in the meal duo to the reward effect of opioids. Poppy shell has a long history of medicinal use in China, and it continues to be used widely in clinical practices. It is the only Chinese medicine decoction substance in the national narcotic drug management catalog , althougThe repeated and complicated detoxification process for opioid addicts and the characteristics of addicted patients who often lie makes it important to remain vigilant in clinical practices to identify addicts who are aware that consumption of foods containing poppy shells can give positive urinary inflammatory test and use this fact as a cover to secretly consume heroin. According to the relevant provisions of Article 33 and Article 47 of Chapter IV of the Drug Law of the People' Republic of China, the duration for community drug rehabilitation for drug addicts is 3 years or even 2 years for compulsory isolation. For the staff involved in clinical practice in the process of drug law enforcement, it is critical to establish a process to distinguish whether positive urinalysis is caused by heroin to avoid awarding erroneous punishment. The metabolites of heroin are morphine and 6-O-monoacetylmorphine . Past stThe Food Safety Law of the People's Republic of China has specified that the addition of poppy shell to the food in any form is illegal. In fact, in 2008, the Ministry of Health of China listed poppy shells under the “List of Non-edible Substances and Food Additives that May Be Illegally Added in Foods (First Batch)”. Adherence to this statement prohibits illegal additions of poppy shells to foods and strictly regulates their use. In China, the catering industry is quite prosperous. As hot pot is much loved by the Chinese people, it is served quite frequently on the streets of cities. It is impossible to perform routine urinalysis on the general population to determine whether poppy shells exists in the hot pot served across cities unless the patients receiving MMT treatment are followed up at the drug treatment clinic. Although prohibited by law, some people still prefer to take the risk of using poppy shells for economic benefits. Therefore, we suggest that the government should strengthen the propaganda of the legal system and improve self-discipline among catering practitioners, as well as actively develop rapid detection technology for hot pot soup to identify the illegal addition of poppy shells in hot pot, strengthen the punishment for illegal abuse of poppy shell, and minimize the harm of opioids to the population through various treatment measures.For MMT patients, who are considered extremely special in China, if the urine test is positive, they should be subjected to stricter scrutiny so as to confirm possible relapse or failure of the community detoxification process. This approach leads to psychological harm and confidence frustration, especially in patients with good MMT community treatment compliance and relatively complete social function. Therefore, great attention should be paid to such patients' diet and medication and weekly urine tests should be conducted for them according to the clinic requirements. In case of accidental positive results, we must look for the cause of positive results and clarify through various processes in order to avoid unnecessary hassles for the patients.The original contributions presented in the study are included in the article/supplementary material; further inquiries can be directed to the corresponding author.Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.XL made substantial contributions to conception and design of the study. JM and KZ drafted and revised the manuscript. YH was responsible for collecting case information and subsequent follow-up interviews. XL gave final approval of the version to be published.This study was funded by the Wuhan Health and Family Planning Commission  and the Wuhan Health Commission .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Black Lives Matter campaign has highlighted issues of race and racism that are present in all parts of our communities and organisations. We stand in solidarity against racism in all forms and acknowledge that organisations, including those within the publishing world, need to do more. BJGP Open must ensure that ethnic minority voices are heard and represented within our leadership, board members, fellows, editorial staff, readers, and authors.1 The statistics on under-representation of ethnic groups at all levels of publication and academia make uncomfortable reading, and the reluctance to openly acknowledge this is delaying progress.3 The tokenistic phrases and well-intended platitudes on the need for greater diversity must be matched with measurable action. As a journal, we need to play our part and demonstrate a commitment to meaningful progress on this issue.The BJGP Open has set out an ambitious programme of work on race and diversity. It starts with this special issue, in which we have collated individual and collective experiences on racism in primary care alongside relevant policy and practice submissions. GPs, trainees, medical students, and academics have shared their recent lived experiences of the everyday racism that ethnic minorities face in our discipline today.4 These challenging experiences range from a GP being doused in alcohol by a patient;5 a medical student repeatedly overlooked due to race;6 and a GP required to ignore racial slurs at the request of a senior partner.7Where is the accountability, they ask?Accordingly, 8 They highlight their approach to bringing about long-term institutional change, which they suggest is necessary to equip medical students with the tools to manage an increasingly diverse population. Bhatti and colleagues in their viewpoint provide us with another historical perspective, emphasising the substantial contribution of migrant labourers to different roles in primary care.9 The authors highlight the Medical Workforce Race Equality Standard (MWRES) in narrowing the gap in workplace experiences and opportunities, and call for the inclusion of general practice to bring about sustainable change. Sarfo-Annin takes this further in a commentary that outlines the case for affirmative action in reducing racial exclusion by enabling structural changes to achieve representative diversity, especially for leadership positions.10 They argue that the term ’BAME’  had too broad a definition to be useful as a metric for ethnic inclusion because of significant heterogeneity in the experiences of different minority ethnic groups. While acknowledging the complex challenges, they call for more detailed data on the ethnicity of GPs to raise awareness, generate dialogue, and enhance the organisational accountability that might improve inclusivity. Ikpoh's article then presents a very personal trainee perspective.11 Next, Gopal and colleagues contribute a discussion on the effect of racial disparities on GPs, and question whether the non-minority workforce needs to go further in acknowledging personal prejudices and implicit biases.12 The authors suggest that improvement will come in the form of greater diversity in leadership and governance structures.Hartland and Larkai describe in their article the concept of decolonisation in reforming the medical school curriculum, and explain why this is important in addressing unconscious biases.Their suggestions on the importance of diversity in leadership and governance have not gone unheard. At our journal, we have made strategic appointments, including a new Editorial Board which represents one of the most diverse in the history of our larger journal family. Similarly, our team of editorial fellows and medical students reflects racially diverse voices. Led by our Editorial Board, we have additionally established a new mentoring and outreach programme for students from around the world, particularly those from low sociodemographic and minority backgrounds, who are less likely to attend higher education. We offer virtual placements, student projects, and one-to-one mentoring. This is alongside a mentoring programme to support authors from low- and middle-income countries, who are less likely to have manuscripts accepted across biomedical journals. We provide opportunities for additional feedback and support in the preparation of their manuscripts.13 This is summarised in an editorial included within this collection by Professor Amanda Howe (President), Professor Martin Marshall (Chair), and Dr Valerie Vaughan-Dick (Chief Operating Officer) of the RCGP. They summarise recent learning, recognise the diversity of the membership, and put forward plans on tackling racism within the discipline.We are additionally opening a period of consultation from 1 December 2020 to 11 January 2021 on the collection of anonymised sociodemographic data, including ethnicity, from all our authors at the point of submission. This will allow us to openly report submissions and acceptance rate by ethnicity, to identify unconscious biases, and to address these as necessary through, for example, blinding of peer reviewers and editorial staff to author details. In turn, we hope that other scientific journals might be encouraged to follow suit. We are already working with colleagues at other journals on our ‘research into publication science’ programme. We are running several studies to collate data and scrutinise evidence on publication science around sex and ethnicity. These strategic programmes are aimed at ensuring that when authors submit their work to us, it is the quality of the scientific content and not race or, indeed, sex that determines acceptance. Our efforts at the journal have been complemented by a diverse programme of work currently being carried out at the Royal College of General Practitioners (RCGP).Research, alongside the lived experiences shared in this collection, emphasises that racism is very much alive within primary care, and that the world around us is shaped by structural and systemic racism. The expectation in all aspects of primary care is to maintain the highest level of professional and moral standards. It is incumbent upon all of us in primary care to be aware of the issues around race, to speak up, and to support each other in tackling this challenging issue.https://bjgpopen.org/letters, or email us at BJGPOpen@rcgp.org.uk.If you would like to contribute to the discussion or comment on our consultation, please tweet us @BJGPOpen, respond through our online e-letters


The purpose of this review study is to explore the existing research focusing on the impact of foreign language learning among healthy seniors on their cognitive functions from the positive psychology perspective. The methods are based on a literature review of available sources found on the research topic in two acknowledged databases: Web of Science and Scopus. The search period was not limited by any time period since there are not many studies on this topic. Altogether seven original studies were detected. The findings of this review study thus reveal that foreign language learning (FLL) has a positive impact on the maintenance and/or enhancement of cognitive abilities irrespective of age. In addition, the FLL courses seem to offer new opportunities for healthy seniors in the area of socializing and integration into society, which consequently may positively affect their overall well-being. Furthermore, the research shows that it is partly through the stimulation of social well-being that the cognitive effects of FLL might be observed. Cognitive aspects of older age are to be further investigated, including the importance of learning a foreign language, as basically all research conducted proves at least some maintenance or even improvement of cognitive functions of older people when starting intensive language training. Consequently, in the coming decades the increase in the number of people in the age-group of older adults will be dramatic and unprecedented  but does not affect crystallized intelligence  Klimova, . FindingIn addition, learning a foreign language is considered to improve the quality of human life because, as proven by research, there is a definite correlation between life-long learning and the general well-being of a person ; to investigate feasibility of a FLL course among healthy older people; and to test the keyword method for acquiring new L2 vocabulary.The number of subjects in the above-mentioned studies ranged between 10 and 153 healthy older individuals. Except for one study (Pfenninger and Polz, The findings of these studies revealed that FLL has a positive impact on the maintenance and/or enhancement of cognitive abilities (Gruneverg and Pascoe, As seen in Wong et al.  conductemaintenance of cognitive skills rather than their improvement. Intuitively, as well as supported by various studies, we can accept that FLL will have some positive impact on cognitive skills. However, the most important question is that to what extent it will influence the cognitive skills in the older population. The research results do not confirm the hypothesis that the learning of a foreign language will naturally enhance cognitive skills. Nevertheless, they yield significant findings suggesting a possible impact of FLL on the maintenance of cognitive skills, i.e., there was, at least, no observable decline of cognitive functions in the test group. Regular cognitive training, such as FLL, thus, will not function as a way to improve cognitive skills but rather as an efficient tool for their maintenance. Therefore, FLL can sufficiently contribute to a non-pharmacological strategy in preventing the onset of cognitive decline.Valis et al.  do not cFurthermore, short-term language training in healthy seniors can lead to a significant improvement in global cognition with increased functional connectivity in the right inferior frontal gyrus, the right superior frontal gyrus, and the left superior parietal lobule. These findings are part of the current neuroscience breakthroughs that reshape neural networks through foreign language training. Bubbico et al's  recent sThe results of this review study also reveal that FLL in older adults contributes to establishing strong social ties between the participants, promoting social interaction and integration. Naturally, most language classes are held in classrooms, facilitating regular physical meetings of participants. This helps to develop social connections among participants and instills in them a sense of participation. The older generation often suffers from social isolation, which can possibly be an important factor of lower level of well-being and a source of depression (Popa-Wagner et al., In light of expected global demographic changes, the established cognitive and mental benefits of FLL in old age, and the role of FLL in the improvement of general human well-being, universities should offer relevant courses for the third-age learners. The breakthrough research by Singleton and Pfenninger  moves ouYi-Yin  researchMoreover, there is an emerging trend within learning psychology and related disciplines—the use of mobile technologies in the learning process. Again, there is a plethora of literature on the use of technology in basic, high school, and university education but little on the use of technological tools by older learners. Some introductory experimental findings are, however, described by Ware et al.  and WongFurther pedagogical implementations of the findings will be important. Moreover, pedagogy and psychology of learning ought to try to find new pragmatic approaches and methodologies in the light of both expected global demographic changes and the possible positive outcomes of FLL in old age. There is immense scope for FLL in old age and we need to create courses that will incorporate earlier research findings with anticipated future developments in the field Kliesch et al. .Introduction to Psycholinguistics. Understanding Language Science (Traxler, An Introduction to Psycholinguistics by Steinberg and Sciarini (It is important to highlight that even authoritative textbooks on psycholinguistics such as Traxler's Traxler,  totally Sciarini  where soSciarini . It is fThe above-mentioned research has several limitations. The findings are usually not very systematic, the author applies different methodologies, and the results are difficult to replicate and difficult to verify by further research (cf. Melby-Lervag and Hulme, The findings of this review study thus reveal that FLL has a positive impact on the maintenance and/or enhancement of cognitive abilities irrespective of age. In addition, FLL courses seem to offer opportunities to healthy seniors for socialization and integration into society, which may positively affect their overall well-being. Furthermore, research shows that it is partly through the stimulation of social well-being that the cognitive effects of FLL might be observed.The topic of FLL in old age has attracted widespread attention of scholars in the past few years. The topic holds great promise for further development especially in the identification, analysis, and development of learning strategies to maintain—or even improve—cognitive and psychological aspects of older people's life. Foreign language education for older generation might offer crucial non-pharmacological strategies for healthy aging—a topic of utmost importance due to the negative demographic trends both in Europe and in the so-called developed world. However, further research is needed.From a positive psychology perspective, future research should focus on what kind of positive instruction should be given to older adults so that we can understand them in a better way. It is also important to develop methodologies to improve old people's sense of accomplishment in the learning process. Last but not least: investigating how to improve the pleasure of learning in the older generation of learners because it is one of the most important aspects of their language education.All datasets generated for this study are included in the manuscript.BK and MP drafted, analyzed, wrote, and read the entire manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.