This 360The study was conducted in the Raisen district of Madhya Pradesh, India. The grounded theory approach was applied for data collection and analysis using in-depth interviews, and focus group discussions with stakeholders representing from health system (including the ASHAs) and the community . A key group of diverse stakeholders were convened to utilize the nexus planning five domain framework  to prioritize the challenges and co-create solutions for improving the home visitation program performance and quality. The nexus framework provides a systemic lens for evaluating the success of the ASHAs home visitation program.The societal (caste and economic discrimination), and personal  issues emerged as the key constraints for completing home visits. The programmatic gaps in imparting technical knowledge and skills, mentoring system, communication abilities, and unsatisfactory remuneration system were the other barriers to the credibility of the services. The nexus planning framework emphasized that each of the above factors/domains is intertwined and affects or depends on each other for home-based maternal and newborn care services delivered with quality through the ASHAs.The home visitation program services, quality and impact can be enhanced by addressing the social-cultural, organizational, educational, economic, and physical nexus domains with concurrent efforts for skill and confidence enhancement of the ASHAs and their credibility. Home visitation is an effective and community-wide acceptable model to provide intensive care during pregnancy, childbirth, and postnatal care to improve maternal and child health outcomes , 2. MostASHAs  are the community health functionaries stationed in the villages  and over a million ASHAs are working in 600000 villages across India . As partStudies have shown that when an adequate number of home visits are made for newborns and infants accomplishments of the tasks assigned to community health workers lead to both better physical and cognitive development and early identification of sickness. High-quality home visitations also decreased the mortality and morbidities in this age group –17. An AWe applied the nexus planning framework (NPF), which is based on 360-degree assessment of the challenges, interlinkages, synergies and, trade between the challenges with emphasis on cross-sectoral sustainability and enhancing the socio-economic-cultural-and organizational resilience against current and future barriers. The NPF method was a further refinement of the traditional formative component recognizing the importance of sub-group and sub-constituencies of the stakeholders and attempts to incorporate their respective concerns, hesitancy and, fears and unique solutions .The study was conducted in Raisen district of Madhya Pradesh, India from October 2016 to September 2018. Madhya Pradesh has one of the highest neonatal and infant mortality rates in the country and is one of the eight socio-economically backward states , also referred to as the Empowered Action Group (EAG) states . In MadhThe study had two phases data collection, analysis and, synthesis. During Phase I (formative research), we applied the qualitative research methods using grounded theory for data collection and analysis. In-depth interviews (IDIs) and focus group discussions (FGDs) with various participants were conducted at their respective locations. Phase-II: Data from Phase-I were used for conducting the multi-stakeholder nexus planning (NP) exercise.Community engagement: Before commencing our community activities, we had a series of meetings with village leaderships (Panchayat members) in the four study blocks to explain to them the purpose and methods of the study and obtain their buy-in. We purposively selected the respondents for IDIs and FGDs ensuring the representativeness at different levels  . We purpWe collected data using pretested semi-structured IDI and FGD guides developed by the investigators/authors, a multi-disciplinary team. A team of four female social scientists trained in qualitative data collection conducted the IDIs and FGDs at places convenient to the interviewee and no observer was allowed. The IDIs and FGDs were conducted in the local language (Hindi) and audio recorded with consent. Some of the IDIs with health managers at the state and national level were in English; these were also recorded. Study investigators  conducted the IDIs at the national, state and district levels and facilitated the FGDs. Senior researchers  with at least 15 years of experience in qualitative research, supervised data collection, and analysis. Most of the IDIs and FGDs lasted for about one hour (range 50 to 120 min).All IDIs and FGDs were transcribed  and then translated into English. The transcriptions/translations of all IDIs and FGDs were entered using INCLEN qualitative data analysis software (IQDAS)  for systNexus approach is currently used in a large number of sectors to define solutions to complex, multidimensional, and layered challenges. Under the nexus approach, interlinkages, synergies, and trade-offs are analyzed, with the aim of identifying solutions and improving the performance of ecosystems. Thus, nexus planning emphasizes cross-sectoral sustainability and enhances socio-economic-cultural-organizational resilience against current and future challenges. We have used NPF as a participatory co-creation process to ensure ownership of all stakeholders including their sub-constituencies in decision-making and bringing about accord among all stakeholders including the program implementers to improve the performance of ASHAs, particularly for home visitations under HBNC and HBNC Plus program. NPF systematically focuses on the challenges and attempts to identify the possible solutions under five nexus domains: social-cultural, economic, physical, organizational, and educational , 32–34 .The nexus planning process had three steps after the initial formative research component using qualitative methods (Phase I), which identified the barriers and facilitators to the home visitations by the ASHAs from a large number of stakeholders including the mothers and ASHAs . The datAn extensive discussion was held between the investigators, field staff, and Panchayat members to identify essential sub-groups/constituencies of all stakeholders, which had different perspectives and social dynamics at the ground level. Through the discussion, then it was decided to conduct three nexus meetings/consultations considering the caste groups of the community and the frontline workers and larger community of service providers; one each including the representatives from lower and higher/upper castes  and the third with mixed representatives drawn from all caste groups.Each of the caste-specific nexus planning meetings/ consultation had 20–30 participants drawn from the same caste group . The meetings were facilitated by the authors. The objectives of these nexus planning meetings/consultations were to discuss the findings from Phase-I (formative research); validate the sub-group specific observations emerging from the data analysis; identify the challenges categorized according to the nexus domains and suggest solutions appropriate for their respective caste groups.Following the caste-specific nexus planning meetings/consultations, the final larger heterogeneous stakeholder group consultation (59 participants) was organized to bring synergy between the perspectives of the two sub-groups, smoothen the points of disagreement and develop final recommendations for improving the performance of the ASHAs in the communities. This nexus planning method is a further refinement of traditional formative components recognizing the importance of sub-group and sub-constituencies of the stakeholders, bringing about synergies, accord and identifying the points of negotiations so that the recommendations incorporate their respective concerns, hesitancy and fears, and unique solutions.The nexus planning process was facilitated by two experts, who are the innovators of the process  and authors having experience in community engagement. The participants for nexus planning meetings included: (i) community stakeholders engaged in the process of home visitation directly or indirectly i.e., mothers, family members, village leadership ; (ii) elected village leadership , Village Health, Sanitation, and Nutrition committee (VHSNC) members; (iii) representatives from education, revenue, and administration departments; (iv) respondents from the health department– ASHAs, ANMs, doctors from PHC/CHC and Chief Medical Officer of the district, ASHA supervisor; and (v) department of women and child welfare-AWWs. Three NPMs were organized: two preliminary NPMs considering the social demographic sensitivity [the community stakeholders were purposely drawn from low (first NPM) and high castes (second NPM)] and the third with a mix of community and representatives from the health system . No suchFirst  and second  NPMs reviewed the findings of the IDIs and FGDs and indicated their views about the correctness of the data and its interpretation. The rationale of giving importance and hearing to all the sub-group stakeholders/constituencies brought out items and matters which required joint discussion to arrive at a mutually acceptable way forward. The challenges faced by ASHAs from forward and backward communities were different and had to be handled in a manner that required suggestions from both sides.The third NPM  discussed the barriers and strategies for overcoming these in a harmonized, negotiated, and comprehensive manner. Each NPM had a similar work process. The objective of the initial plenary of 60 min, was to apprise the heterogeneous audience of the perceptions of the diverse sub-group stakeholders and emerging themes that required careful attention. The group was divided into 3 smaller groups and each comprised mix of community sub-groups/constituencies and geographies of the district along with health providers. Nexus planning charts were used primarily to keep the discussion on track document discussions according to specific domains, and develop final recommendations for improving the performance of the ASHAs in actual field settings . FinallyThe NPM facilitators noted down the observations and comments of every participant on ‘post-it/sticky notes' and collected these on the nexus domain chart. The findings from the first and second NPMs were shared with 3rd large group NPMs. The final plenary of the 3rd NPM helped in the co-identification of the barriers, and co-creation of the solutions and recommendations under the five nexus domains i.e., socio-cultural, physical, organizational, economic, and education.Data from Phase-I has been organized under the nexus domains with the emerging themes and sub-themes along with an illustrative statement from the participants.The majority of the state and district level stakeholders, ANMs, and approximately half of the ASHAs identified socio-economic divide and caste/religion-based discrimination making the home visitations difficult and the reluctance of families to accept the health and wellness messages for childcare and more so for male children. Socio-cultural beliefs such as seclusion of post-partum mother and child and belief in the tradition of the‘evil eye effect' also made it difficult for ASHAs to deliver the desired services.Some refuse to put the child in the weighing bag. They say that you took the weight of the Muslim child, the Scheduled tribes (ST) Child and now you will put our child in the same bag” [ASHA Sahyogini] “She is from a rich family. Why will she will come to a low-income family house?” [Mother non-utilizers]“Some are Harijan (Scheduled caste), and some are Vasur (scheduled caste)?, so she differentiates. She is not comfortable coming to our house. She does not touch our child.” [Mother non-utilizers]“Stakeholders from the administrative hierarchy and community perceived trust deficit and lack of respect and credibility of ASHA due to lower education status, inadequate training, and lack of confidence demonstrated while communicating with the family members. Similarly, the community questioned the ASHA's credibility, when the family experienced ‘inadequate or suboptimal' services at the health facility to which ASHA referred them. Several elders in the family preferred traditional childcare methods over ASHA's suggestions. Common superstitious beliefs such as ‘Sutak' (prohibitions observed during post-partum period), when the mother-neonate are confined indoors, were used as an excuse to refuse both contact/examination by the ASHA and referral. The front-line workers  perceived that it was difficult for ASHAs to convince the community and families about immunization and the associated minor side effects. Families also showed deep-rooted resistance in following advice, such as play and communication with the child and washing hands with soap, which considerably differed from their existing practices and were perceived as irrelevant to them. Approximately half of the non-utilizers mothers complained of the lack of resources required to follow ASHAs' advice. We also found a better understanding of utiliser mothers' knowledge of program components like exclusive breastfeeding, IFA syrup, hand washing, and ORS preparation when compared with the non-utilizers mothers.People doubt her motive when she visits their house again and again”. [AWW] “ASHA instructs mother what all things she should follow after delivery. Family members get irritated that why she is instructing her”. [ASHA Sahyogini]“We don't expect much from ASHA since she doesn't know much herself.” “If ASHA asks them for vaccination and child has a mild fever, then they immediately say no. Few people don't behave well with the ASHA.” [ANM]“The majority of the ASHAs felt that they were caught between their domestic  and professional responsibilities. According to the ASHAs, the non-availability of a mother at the time of the home visit or the mother's engagements with social responsibilities posed additional challenges. Mothers were unhappy that most ASHAs did not maintain a timetable for upcoming home visits or were informed of a home visit beforehand. Many mothers went back to their natal homes after childbirth for 6–12 weeks. As a result, either the HBNC visits remained incomplete, or HBNC Plus visits began late.I was having an issue with my mother-in-law because she repeatedly kept asking where I went. I have to tell her that I have to measure weight by going house to house as an ASHA responsibility. Then she allows me to go.” [ASHA] “Other issues are mother goes to her maternal place along with child or if the child is underweight then she is referred to hospital and sometime ASHA is herself tied up with some work in such cases she is not available to make home visits.” [ASHA Sahyogini]“The health supervisors expressed concern about the ASHA training including residential training (staying away from the residence), curriculum design and its poor translation; and organization of practical skill training. However, most ASHAs and ASHA supervisors did not point out any difficulty in attending residential training. ASHAs and their supervisors reported that the training was insufficient and unsuitable; difficulty in comprehending technical terms related to many health and medical science by the ASHAs with less formal education, the content of the curriculum material, and the pace of knowledge imparting procedures in real-life situations.As and when we come back home, then we cannot learn further anything under the supervision and become busy with village and family chores. And after some time, many forget their training.” [ASHA] “Personally I feel ASHA is not a proper person to identify neonatal sepsis. We have trained we have to define the criteria for what are the danger signs and how to identify them. I think it is difficult for women from the field with a limited knowledge.” [State Officer]“ASHAs hardly retain about 50% of training.” [ASHA Sahyogini]“One of the most critical determinants of ASHA's credibility and acceptability in the community was its technical competence and communication skills. The ASHAs' inability to recognize sickness in children and the rationale and basis of nutritional and play therapy made it challenging to communicate messages correctly, effectively, and confidently. State and district level stakeholders acknowledged the poor quality of home visits because of the ASHAs' technical and communication competence challenges despite frequent contact. Although half of the ASHAs responded that they don't experience any difficulty performing HBNC/HBNC Plus responsibilities, almost a similar proportion accepted that they encountered problems while making home visits. ASHAs acknowledged that some of the poor response from mothers and family members was on account of their inability to communicate clearly and effectively. Some ASHAs reported having difficulty in performing technical tasks such as measuring temperature, weighing new-born, and making growth charts.I don't have enough knowledge to know whether he has a fever or not. We make an idea by seeing whether he is playing or not. [ASHA] “She is not able to explain when and how much IFA syrup is to be given and why it should be given”. [Block Medical Officer]“ASHAs hardly retain about 50% of training.” (Echoed by many ASHA Sahyoginis)”“She is unable to form connectivity. When she goes for a home visit, she talks about general household things such as cooking and does not discuss health services. They forget total about health and wellness issues. It is the main gap.” [District Level ASHA Trainer]“ASHA supervisors claimed that they monitored and supported the ASHA's activities. State and regional managers, however, acknowledged that the supervision of ASHAs was both poor and unsatisfactory because of vacancies in the supervisory cadre (ASHA Supervisors). The HBNC/HBNC Plus performance formats/reports were reviewed infrequently and supervision was of limited utility. The program managers strongly contended that state and district-level officers should also visit the field to understand and address the managerial bottlenecks. Block and community-level stakeholders mentioned the availability of a limited mobility budget for monitoring was also a hurdle in program monitoring.Supportive Supervision is one of the weakest links in-home visitation, which was the strongest in the Abhay Bang Gadchiroli project.” [National level stakeholder]. “At the block level, we have to check the filled forms; we are unable to check it properly due to a high number of forms being submitted at the block level every month. It becomes difficult to review all the forms properly.” [Block community mobilizer]“ASHAs, their supervisors, and senior officers consistently accepted that the tasks assigned to ASHAs were complex. The ASHAs were imparted limited exposure to planning and prioritization exercises during training. Not infrequently, ASHAs re-prioritized their work based on directives from higher-ups for health and non-health exigencies beyond the planned activities. Vacancies and rapid turnover among ASHAs and vacant positions in supervisory cadres added to poor planning and management.ASHA has many other responsibilities, prioritization and non-adherence to the schedule should be seen in that context.” (Echoed by many ASHA Sahyoginis) “There are 5-10 percent vacancies for the post of ASHA Sahyogini, ASHA, and BM (block mobilizer)” [Programme Officer]“Irregular and insufficient supply of products (such as ORS and IFA syrup) and stationery adversely affected the HBNC/HBNC Plus related functioning of the ASHAs. The managers attributed this to distribution process-related challenges and delays by ASHAs to indent the supplies.Last year in January, my BP and weighing machine were not working. So I deposited in last February, and I got this February.” [ASHA] “ASHAs are remunerated on the basis of the completed tasks (such as vaccination or home visits). Most ASHAs complained about the delay in receiving the incentives. The factors identified for the delays included: late receipt of funds, inability to fill the records appropriately, and refusal by the families to comply with their advice regarding immunization and sickness and hospital referrals. On the other hand, supervisors pointed to the challenges in releasing the incentives due to incorrect and incomplete maintenance of records and mismatch between claims and feedback from the field; shortage of funds was infrequent and not considered as significant concern. While most of the ASHAs and ASHA Supervisors reported receipt of only 50 percent to 70 percent of their entitled monthly incentives, the managers at the district level didn't agree with it and claimed that the full amount was distributed. The family members of ASHAs were reportedly unhappy about the lesser amount of incentives, delay in payments, and being paid less than other frontline workers ; which pose challenge in obtaining adequate support from their own family itself to perform the duties.We get money after 2 or 3 months, and it's not monthly. Everyone gets after this much time. When we say this to sir, he says that I am the only person managing it, so delay happens, and there is no such work for which we should pay early.” [ASHA] “The ASHAs and several program managers at different levels acknowledged the hurdles related to reaching outlying and hamlets, tribal areas, and areas with hilly terrain. Few of the ASHAs were not from the same village communities  and therefore needed to travel to their place of work.Tribal population is living in far off areas. So need a strategy for better reach”. [NIPI Programme Officer]“Some villages are too big, and houses are scattered. The area might be split into smaller ASHA jurisdictions.” [PHC Medical Officer]“The details of the discussion held during the preliminary two caste-specific NPMs are presented in The larger NPM group framed the recommendation at two levels: (i) administrative and organizational level; and (ii) community/family level. Task-oriented skill-building of ASHAs along with frequent re-orientation through supportive supervision and handholding was considered essential to improve ASHA performance, get her rightful place in her own family and the community, and even reduce caste-based prejudices. This will require re-engineering of the whole training curriculum in a manner that is aligned to the objectives of the HBNC and HBNC Plus programs. The ASHA was expected to prepare a micro-plan for her activities and communicate preventive, promotive, and curative knowledge to the families with confidence and conviction in their homes and community settings. Equally essential was to release the incentive money rightfully due to the ASHAs in a timely and regular manner. The health system was also asked by the nexus group to consider raising the incentive amount or making ASHAs regular salaried employees and consider the possibility of providing them with health insurance. The availability of flexible funds with ASHAs was considered useful for hiring vehicles at odd hours for the transport of sick children and pregnant women when ambulance services were not available. Another significant intervention proposed was increased male engagement in community meetings through village fora like VHND/VHSNC. These fora could help negotiate and reduce social discrimination and also strengthen social accountability .The study adds to the existing knowledge that societal issues and personal challenges for ASHAs at their home and community fronts are among the more important barriers/challenges that prevented them from completing home visits and associated tasks with quality. The other reasons for incomplete age-appropriate home visits included gaps in the monitoring of ASHA's performance and mentoring system. Almost half of the ASHAs also accepted their lack of confidence in technical knowledge and communication skills. These factors shook community confidence in her capabilities and the importance given to her advice. The field-level staff including the ANMs, AWWs, block mobilizers, and ASHA supervisors strongly endorsed ASHAs viewpoint with particular emphasis on their social and domestic challenges, and importantly these were often overlooked. Mothers, even those never visited by ASHAs at home, felt that, ASHAs also lacked planning skills and consequently did not get the desired support from families for optimum performance.The interconnectedness and complexity of the challenges in different sectors and aspects of human ecosystem have led to the recognition of the importance of transformative approaches in addressing and achieving sustainability . Nexus tNPMs unambiguously recommended managing all the domains synchronously if the ASHA performance was to improve. The study data recommended interventions at the communication, organizational and educational levels to improve the quality of visits through enhanced skills and confidence of the ASHAs. This would necessitate reengineered training and follow up mentoring methods to enhance her credibility and respect in the community and abate to a certain extent the social and religious prejudices against the ASHAs. The social and family commitments of the ASHAs are important and complex challenges and need to be handled through engagement with the community at different levels e.g., Panchayati Raj members and the participation of men and elderly women in their families to help in negotiating ASHA's usefulness to the community with reduction of social discrimination; and enhancing her stature and respect in the community through reinforcement of her technical and communication skills. Incentives alone are insufficient to motivate the ASHAs for better performance as was done for HBNC Plus program. Timely release of due remuneration can be additional factors for motivating the ASHAs and soliciting their family support. The primary focus and responsibility of ASHAs can be better defined: if it remains maternal and child health activities, regular feedback, and monitoring will make them feel more responsible as well as accountable for different components of maternal and child health services.The majority of the ASHAs in the current study perceived conflict between their domestic and professional responsibilities. Several previous studies have also shown that the personal needs and family commitments of community health workers interfered with their ability to make home visitations regularly and at times convenient to the beneficiaries –39. DuriThe ASHAs have to navigate societal and cultural prejudices during their fieldwork  and housMentoring and hand-holding emerged as important tools for the ASHAs' performance and quality of home visitations in several studies. Gilson et al. reported that high-quality supervision helped in the restoration and sustenance of trust of the community in the health system and its services . In a stComplex interconnected challenges when addressed singly, at times may reduce one problem while exacerbating others. Studies have shown that tackling the challenges piecemeal has not helped to improve the ASHA's performance , 62. In This study has some limitations. We applied NPF as a co-creation exercise involving a wide range of stakeholders and sectors for inductively developing a comprehensive understanding of the factors affecting home visitations by the ASHA, and the interrelatedness between barriers and potential solutions. We modified the broad principles of nexus planning for health system strengthening and improving the performance of frontline workers in resource constraint environments which also have deeply entrenched social, cultural, and other contextual factors. The rationale of giving importance and hearing to all the sub-group stakeholders/constituencies separately brought out several items and matters which required joint discussion to arrive at a mutually acceptable way forward. The challenges faced by ASHAs from forward and backward communities were different and had to be handled in a manner that required suggestions from both sides. The nexus approach guided us to identify and pursue synergies between health and non-health sectors i.e., Panchayati Raj [local self-government] recognizing their significant function and responsibilities to iron out some of the socio-cultural and economic biases operating at the village level. The feasibility and widespread applicability of NPF can be a concern. As mentioned above, successful NPF processes are dependent on identifying the sub-groups and sub-constituencies strategically for a series of group meetings/consultations. This will require deep insight into the local cultural, social, economic and, organizational milieu. Notwithstanding these limitations, the nexus framework did provide robust findings which can be triangulated with several published studies albeit done in a piecemeal manner from India and other low and middle- income countries (LMIC) settings. NPF has been successfully applied in environment, urban development, scrum methodology, water-energy-food (WEF) nexus approach in the MENA (Middle East and North Africa) countries, and many other areas for achieving sustainable development goals (SDGs) with sector-specific modifications . NPF offIn conclusion, the present study took a 360-degree view of the factors impacting the home visitation and related performance of the ASHAs and nexus planning groups emphatically recommended that each factor had an effect on or was dependent on the other factors and hence the remedies should include a more comprehensive approach rather trying for piecemeal solutions. The study showed that barriers and challenges of ASHAs can be classified under five broad domains. NPF stressed the imperative of approaching these barriers as interlinked challenges and resolution of any one component alone would not facilitate positive change. Future research and implementation agenda roadmap should include simultaneous interventions to improve the technical and communication skills to build the confidence of the ASHAs through reengineered training and follow-up mentoring methods; which is likely to enhance her credibility and respect in the community and abate a certain extent the social and religious prejudices against her. The social and family commitments of the ASHAs are important and complex challenges and need to be handled through engagement with the community at different levels. Another useful research agenda can be to determine the applicability of NPF in diverse settings and health system challenges.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics approval was obtained from the independent Ethics Committee of the INCLEN Trust International, New Delhi [DCGI reg no: ECR/109/Indt/DL/2014/RR-17]. Written informed consent to participate in this study was provided by the participants. Informant identity during the data analysis was kept anonymized. Verbal consent was taken from community representative and individual to participate in the nexus group meeting.NA designed the study. Data curation was done by VD, SJ, AP, RD, SC, KG, SB, BH, MD, RM, RS, and PS. Data analysis was done by NA, VD, SJ, AP, RD, and SC. NA, VD, and SJ prepared the first version of the manuscript. All authors provided comments on subsequent drafts and approved the final version of the manuscript.This work was supported by the Norway India Partnership Initiative (NIPI). [IND-16/0003 study of HBNC plus Project].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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The practice of proper hand sanitization became of utmost importance and one of the best protective measures during the pandemic outbreak of COVID-19. However, misuse of disinfectants can be an overwhelming issue because of increasing demands, public panic, and unawareness, which can negatively affect human health and the environment. Therefore, we aimed to determine whether the outbreak was associated with increased reports of adverse events related to hand sanitizers through the data of adverse events reported to the pharmacovigilance database of the Food and Drug Administration Adverse Event Reporting System (FAERS). FAERS database was analyzed for hand sanitizer reports including alcohol-based and alcohol-free formulations.Adverse events reports associated with hand sanitizers increased significantly by 2020 with variable severity degrees, noting that most serious cases were reported with alcohol-based sanitizers.Based on data mining of the FAERS database, we claim that the increased reports associated with alcohol hand sanitizer use deserve attention. However, FAER’s database has some limitations, such as case duplication and lack of a control group. Hence, further monitoring with more robust sources of data sources is critically needed. Hands might be polluted easily from droplet transmission when direct contact with sneezes and coughs . RegularHence, this study aims to identify and analyze the number of adverse events reported as a consequence of hand sanitizer use in the pharmacovigilance database available to the public.The publicly available FDA's Adverse Event Reporting System (FAERS) reports were analyzed for the period between January 2010 and March 2022. This database is accessible via a querying tool on an online dashboard and downloadable files [The included reports in the FAERS database are organized based on the Medical Dictionary for Regulatory Activities (MedDRA) classification system. Reports of side effects associated with hand sanitizers used for prophylaxis against COVID-19 during the period from 2019 up to 2021 were stratified and analyzed. Also, reports starting from 2013 were included. Data duplicates were identified using case numbers and merged as one case. Duplication of data could be attributed to reporting by multiple caregivers of one patient. In addition, reports submission from pharmaceutical companies is mandatory once ADR is identified . The totA preliminary query using FDA adverse drug events dashboard revealed that about 139 cases reported adverse effects following hand sanitizers used for infection prophylaxis and most cases were with alcohol-based active ingredients. Only a few cases were reported before 2015. The majority of cases were reported in 2020, increasing from 4 cases (2.87%) by 2019 to over 120 cases (86.33%) by June 2021, where sanitizers were used for infection prophylaxis during the COVID-19 pandemic. Demographic and clinical data were reported for most cases (92.8%), with only a limited number of cases  were stated as non-specified  and memory impairment (n = 1). Serious life-threatening adverse outcomes were reported in a few cases (n = 8).Several published studies reported the risk of inhalation of chemical residues during the application of alcohol-based sanitizer to the skin with considerable risk of spoiling the quality of air indoors resulting in potential hazards such as respiratory disorders, nervous system disorders allergic skin reactions, and eye irritation , 13, 16.Therefore, The FDA agency recommended against the overuse of hand sanitizers and the application of sanitizers in an area with well ventilation .There are several limitations in this retrospective study. Using the FAERS database can result in many instances of duplication errors since the same report can be submitted by the consumer and the manufacturer. Additionally, necessary information and adverse outcomes may not be reported in some cases. Furthermore, the publicity and the widespread product use can affect the number of reports with a potential risk of bias. The continuous updates of information in the FAERS database result in variability in the number of individual cases, which may increase or decrease over time.Given the widespread use of hand sanitizers, the remarkable increase in the adverse events related to sanitizer use reported to the FAERS database, and the anticipated continuous use in the future as a prophylactic measure during the era of the pandemic, this study highlights the need for cautious use of disinfectants. Moreover, further monitoring using adjusted methods with less bias is warranted.


The development of craniofacial structures is complex and involves multiple cellular and molecular interactions. We report a case of congenital camptodactyly in a female who subsequently developed chronic tinnitus and temporomandibular joint dysfunction. This report describes the clinicoradiographic features and surgical management of the facial skeletal manifestations, along with postoperative rehabilitation. Furthermore, a concise review of similar literature raises the question of whether this complex of manifestations represents a new entity or a minimal manifestation of a previously characterized syndrome. As such, a possible developmental association between camptodactyly and temporomandibular joint dysfunction is suggested. Temporomandibular joint dysfunction (TMD) is a non-diagnostic general term that encompasses a set of conditions that alter the functional anatomy or physiology of neuro-musculo-skeletal components of the masticatory system . The etiCamptodactyly, a congenital anomaly of the hand affecting less than 1% of the population, is characterized by flexion of the proximal interphalangeal (PIP) joint resulting in finger deformity, most commonly in the fifth digit . TrismusThis report highlights the case of a 25-year-old female with congenital bilateral camptodactyly who had a history of bilateral TMJs disc displacement. Surgical management and rehabilitation of the TMJs, along with a discussion focused on related literature, is presented in this concise report, raising the question of possible developmental associations between camptodactyly and TMDs.A 25-year-old Hispanic female patient presented to the clinic with a chief concern of bilateral tinnitus (more severe on the left side), mild jaw pain, mouth breathing, and bruxism. Upon intraoral examination, bilateral craze lines were noted on the maxillary canines with normal mouth opening (51 mm) with a deviation of the mandible to the left side upon opening. No other teeth or soft tissue abnormalities were detected; however, the patient mentioned that the alignment of her dentition has changed, which may be suggestive of an orthodontic treatment relapse. Extraoral examination revealed bilateral camptodactyly of the fifth digits (little fingers), which was more pronounced on the left hand. With further interviewing, the patient reported curved phalanges of the foot. The patient denied any familial inheritance pattern and was otherwise in good health.The patient's past dentoalveolar history was significant for the following reasons: the patient received orthodontic treatment between the ages of 10 and 12 to correct teeth malalignment and malocclusion. At 20 years old, the patient presented to an orthodontist's office with a persistent anterior open bite, malocclusion, and jaw pain. Imaging studies determined that the patient has a deviated septum with hypertrophic nasal conchae and the presence of a bony spur. She was then referred to an oral and maxillofacial surgeon for further evaluation. At age 21, it was determined by orthognathic specialists that the patient suffers from a stage 4B displacement of the condylar disc of the left and right TMJs. The magnetic resonance imaging (MRI) report indicated medial pole disc displacement without reduction and condylar surface irregularity of both joints  per her previous records. Furthermore, our patient denied any known family history of similar manifestations. A review of related literature on patients presenting with both camptodactyly and TMD over the past four decades revealed that these manifestations occurred in the context of the auriculo-condylar syndrome (ACS) and trismus-pseudocamptodactyly syndrome (TPS) -7,9-14. TPS  is caused by a mutation in the myosin heavy chain 8 (MYH8) gene affecting early skeletal development. All reviewed cases documented camptodactyly and trismus with or without coronoid hyperplasia ,14. In cThe developmental events that govern the formation of the TMJ articular disc and the PIP joint overlap in utero -18 Tabl.We hypothesize that due to the distal location of the TMJ complex and the PIP joint of the fifth digit from the axial skeleton, there may be a temporal relationship between causation and the resulting developmental anomalies. Our patient did not undergo genetic testing, and the possibility of a somatic mutation causing these manifestations should be considered. Presently, there is limited literature discussing the non-genetic association between camptodactyly and temporomandibular joint dysfunction (TMD), raising the question of whether individuals with congenital camptodactyly are at a higher risk of TMDs attributed to a developmental event.A multidisciplinary team was involved in the patient’s rehabilitation post-operatively at ages 21 and 25. Our patient sought treatment through an acupuncturist, a prosthodontist, a physical therapist, and a chiropractor. She noted a release in muscle tension and a reduction in tinnitus through the care of her acupuncturist, with weekly visits. The prosthodontist offered her a pivot appliance that created a posterior separation of the dentition to allow for the articular disc to heal. The patient reported wearing the splint for about 22 hours per day for the first two months. Due to symptomatic relief, the patient used it only at night for another three to five months. This separation presumably caused a reduction in TMJ pain sensation and tinnitus severity. Weekly visits to the chiropractor offered no relief of symptoms of camptodactyly or in the TMJ region. However, the patient noted that chiropractic visits reduced overall upper back pain caused by the forward head posture developed from habitual mouth opening. The physical therapist offered the most benefit, as stated by the patient. The physical therapist began with mandibular stabilization and cervical retraction “chin tucks,” to improve the range of motion. However, while completing the “tongue up” exercise, where the patient is asked to make a clucking sound, it was determined that the patient’s jaw mobility is within normal limits and supported by minimal musculature. As such, the patient was asked to increase her side-to-side jaw exercises to stabilize the mandibular range of motion. The patient also received dry needling by her physical therapist, aimed at relaxing the trapezius and masseter muscles. A prosthodontist evaluated the patient for non-surgical temporomandibular joint dysfunction treatment options as adjunctive therapy to her previous treatments. While load-testing the temporomandibular joints with an anterior deprogrammer, the patient was positive for lingering pain in the joint space. Based on these symptoms, an oral appliance, the pivot appliance, was fabricated. This appliance provides intentional and therapeutic transfer of the mandibular rotational fulcrum from the TMJ to the appliance to unload or decompress the retrodiscal tissue until healing occurs ,20. To oThere are few cases published in the literature on the management of patients with congenital camptodactyly who subsequently developed TMD. In our case, a multidisciplinary team managed the patient over several years, which was accompanied by a significant psychological, functional, and financial burden. Well-controlled studies on an adequate cohort of patients with similar manifestations to our case are mandated to answer the following questions: Are patients with congenital camptodactyly more prone to the development of TMD? Is the anomaly responsible for the TMD symptomology of developmental origin? Answering these questions aid in investigating whether a temporal relationship of developmental origin contributes to these manifestations and whether such an event correlates with the cause of the TMD . This is significant for possible TMD early detection and proper referral in patients presenting with congenital camptodactyly.


The COVID-19 pandemic has caused profound consequences on people’s personal and social feelings worldwide. However, little is known about whether individual differences in empathy, a prosocial trait, may affect the emotional feelings under such threat. To address this, we measured 345 Chinese participants’ personal emotions , social emotions , and their empathy traits during the COVID-19 pandemic. Using the representational similarity analysis (RSA), we calculated the pattern similarity of personal emotions and found the similarity between the positive and negative emotions was less in the high vs. low empathy groups. In addition, people with high (vs. low) empathy traits were more likely to have fearful and sympathetic feelings about the disease-related people  and showed more pattern dissimilarity in the two social feelings toward the disease-related people. These findings suggest a prominent role of trait empathy in modulating emotions across different domains, strengthening the polarization of personal emotions as well as enlarging social feelings toward a set of stigmatized groups when facing a pandemic threat. COVID-19 as a public health crisis has posed a threat to public mental health and social harmony. It has been changing us greatly by adding uncertainty and loss of control to our lives, each of which is known to trigger emotional dysregulation and distress, such as depression anxiety . It is nIt has been well-documented that individual and group differences in cognitive control, emotion-related traits, and biological sex can modulate emotions and the underlying supportive substrates . Among tEmpathy—the capacity to share and understand others’ emotional states—is highly related to the subjective experience of emotions and mirroring others’ emotions . Prior sThe relationship  of the two dimensions of personal emotions has been found to function as an indicator of psychological well-being . Toward A previous study has shown that when exposed to a stressful event , individuals’ positive and negative emotions exhibited more polarization—a higher level of negative correlation . This fiAlthough previous studies have shown that people felt fearful about people and groups related to the COVID-19 disease, such as fear of interacting with people suffering or recovered from COVID-19, toward people related to COVID-19 . MeanwhiPrevious evidence has shown that the psychological process of people’s social feelings toward others is closely related to their ability to empathize . Based oOn the other hand, recent evidence suggests that empathy may account for people’s fear and avoidance of disease-related groups who may carry the virus during the COVID-19 pandemic. For example, people tried to identify people who might pose a potential infection risk when facing a pandemic threat . In lineThe current study aims to examine the impact of empathy on personal and social emotions and their patterns under the threat of COVID-19. Previous research mostly focused on the mean or sum value of different items within the two-valence domains . Moreover, the positive-negative RSM of the high empathy group was more dissimilar than that of the low empathy group  and control clusters . These results suggest that high empathy people may induce more dissimilar and mixed social feelings about the disease-related groups to help them better adjust when facing a pandemic threat.The distribution results showed that the high (vs. low) empathy group showed a higher rate of fear and sympathy for the disease cluster . SpecifiPrevious literature has revealed that individuals’ emotional reactions are related to trait empathy . HoweverPrevious studies found that there was no association  or positAs we have mentioned above, previous studies have found that high empathetic people are more sensitive to threatening stimuli . In lineCompared with low empathy individuals, high empathy individuals reported higher levels of empathetic feelings toward the disease group. The reason could be that high empathy individuals could put themselves in others’ situations and understand their emotions, which may facilitate cooperation under threats . PreviouIn the current results, people with high empathy have complex social emotions toward disease-related people, that is, sympathy (other-oriented) and fear . These results were consistent with the existing research that individuals with high empathy have high self-protection intentions and high other-protection intentions simultaneously at the behavioral level. Specifically, people with high empathy were more willing to take other-protective behaviors during the COVID-19 pandemic . MeanwhiThe current study has the following limitations. First, the current study revealed that high empathy relative to low empathy people reported more negative and positive emotions during the COVID-19 outbreak  but showed less pattern similarity in the positive and negative aspects of the two emotions. However, the underlying mechanisms of the group discrepancy in pattern similarity remain unclear. Taking advantage of neuroimaging technology, researchers could further address whether different neural substrates may be recruited to support the modulation of empathy on personal and social emotions. Additionally, the study was conducted during the recovery period of the pandemic. Although the findings have suggested that there are differences in the pattern similarity of personal and social emotions between high empathy and low empathy individuals during the COVID-19 pandemic, we need to take caution in understanding the moderation of empathy in the patterns of emotions in normal times. Future research is encouraged to manipulate different threat levels (vs. non-threat control) to test whether such moderation of empathy is specific to collective threats or not. Another limitation of the current research is that the factors affecting emotions are complex. Therefore, in addition to empathy, whether other factors can affect the pattern of emotions remains unsolved. Considering that individual and social emotions are also linked with other emotion-related traits [e.g., anxiety and neuroticism, The current study highlights the role of empathy trait in modulating the patterns of personal and social emotions during the COVID-19 pandemic. People with high empathy showed more pattern similarity of negative emotions but less pattern similarity of social emotions about the disease-related people than low empathetic people did when facing such a threat. Our findings enrich the existing literature on understanding the role of empathy in mental health and social cognition in the context of threat.De-identified data and code of the present study are available upon request to the corresponding author.The studies involving human participants were reviewed and approved by the Ethics Committees of the Institute of Psychology, Chinese Academy of Sciences. The participants provided their written informed consent to participate in this study.YM conceived of the project. YM and JZ designed the project. JZ implemented the experiments and collected the data. YH and JZ performed the analyses. YH, JZ, and YM wrote the manuscript. All authors discussed the results and approved the submitted version.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The derangement of CSF circulation impacts the functions of the glymphatic-lymphatic system (G-Ls), which regulates solute trafficking and immune surveillance in the CNS. The G-Ls failure leads to the dysregulation of clearance of waste molecules in the brain and to an altered CNS immune response. The imaging features of dilated perivascular spaces imply the impairment of the G-Ls. We report on the case of a patient with primary progressive multiple sclerosis and dilatation of perivascular spaces, who transiently improved after CSF shunt diversions. The underlying mechanisms remain to be determined and at this stage, it is not possible to link CSF diversion to an effect on MS pathology. However, this observation provides the rationale to incentivize research in the largely unknown area of CSF dynamic disturbances on G-Ls failure and ultimately in neurodegeneration. The glymphatic-lymphatic system (G-Ls) regulates solute trafficking and immune surveillance in the CNS, sub-serving the flow of CSF from the subarachnoid spaces into the perivascular spaces and subsequently into the interstitium, with the aquaporin-4 water channels running it  , performed in 2010, revealed diffuse hyperintense T2 nodular lesions affecting the paraventricular and subcortical white matter; at least two of these lesions showed gadolinium enhancement in T1-weighted images. A coeval MRI of the spinal cord showed nodular lesions involving the dorsal columns, at the C2 and C3 levels. The blood tests were within physiological parameters, while the neurophysiological examination revealed changes in visual evoked potential and somatosensory evoked potential from the left median nerve. Oligoclonal IgG bands at isoelectric focusing occurred in the CSF. The clinical and paraclinical findings led to the diagnosis of MS. Methylprednisolone provided the patient with some improvement. Immunomodulatory treatments with interferon-beta and glatiramer acetate were started and later discontinued due to intolerance. After 16 months of continuous neurological impairment, the patient was diagnosed with primary progressive MS. An MRI performed during the same period revealed a stable picture. She was voluntarily tested in another hospital for cerebrospinal venous insufficiency in 2012. A severe cerebrospinal venous insufficiency was diagnosed, and she underwent percutaneous transluminal angioplasty at the level of the internal jugular veins. She had about 2 years of clinical benefit after the procedure, which paralleled normal anatomic and functional conditions of jugular veins according to the echo color Doppler examination and stability of MS lesions at MRI. Subsequently, her neurological condition deteriorated gradually. Sonographic findings suggested a recurrence of chronic cerebrospinal venous insufficiency (2014). At the age of 38, the patient came under our observation  with a dAware of the anecdotal nature, potential placebo effect, and possibly unrelated and unknown factors, this case suggests the effect of CSF diversions on the MS patient's clinical improvements. The mechanisms and factors underpinning the CSF shunt-mediated improvements of the MS symptoms remain to be determined, at this stage. CSF diversion, decongesting perivascular spaces, may have ameliorated glymphatic functioning and interstitial removal of proinflammatory molecules from CSF and in so doing, downregulating local inflammation. This is in line with the Louveau et al. hypothesis that the modulation of CSF drainage through the meningeal lymphatic vasculature might reduce the quantity of CNS antigens entering the related lymph nodes, resulting in the downregulation of the autoimmune response  for the publication of any potentially identifiable images or data included in this article.AS, BP, and PG have made substantial contribution to the conception of the study. PG, FL, BP, AR, GL, CN, and GD have drafted the work or substantially revised it. All authors contributed to the article and approved the submitted version.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.Videos of a patient with primary progressive multiple sclerosis imaging features of dilated perivascular spaces who underwent cerebrospinal fluid diversions.


N = 54) from three breeds, Holstein-Friesian (HFR), Jersey (JE), and KiwiCross (KC) in different lactations  and with different breeding worth index values (103 < BW > 151) were selected. The cows were managed through a rotational grazing scheme and milked once a day at 0500 hours. The cows grazed mainly pasture and consumed additional feeds (maize silage and turnips) in the summer and autumn seasons. AfiCollar was used to record grazing and rumination behaviors (min/h) in the individual cows throughout the lactation period (~270 d). The time neither utilized for grazing nor rumination was counted as idling behavior (min/h). A repeat measure design with PROC MIXED was performed in SAS considering the effects of breed, lactation, individual cow, the hour of the day, season, day within the season, and supplementary feed within the season to evaluate the difference in grazing, rumination, and idling behaviors. Hour of the day, season, day within season, and supplementary feed had significant effects on grazing, rumination, and idling behaviors. Regardless of the season and supplementary feed, cows spent most of the daytime grazing and most of the nighttime ruminating. Grazing activity remained consistently high throughout the day with two peaks around dawn and dusk and a short peak around midnight. Rumination activity remained high from the late evening until early morning. Grazing and ruminating patterns were similar between different breeds and lactations, however, JE cows grazed slightly longer than HFR and KC, and first-lactation cows grazed slightly longer than those in higher lactations. The onset and cessation of grazing activity by the cows were adjusted according to varying day lengths by season. Cows finished grazing earlier when they consumed additional supplements or silage along with pasture. Cows from different breed groups and lactations spent most of their 24 h grazing followed by ruminating and idling. Season and supplementary feed potentially affected the variations in behavior time budgets. These findings should support improving measures for grazing management to address pasture allocation and additional feed demands, and animal welfare in varying environmental and/or managemental conditions.This study investigated the variations in the temporal distributions and the lengths of times utilized for grazing, ruminating, and idling behaviors by grazing dairy cows over 24 h. Spring-calved lactating dairy cows ( These findings could support the advancements in the measures for pasture and additional feed management to address individual animals’ requirements and could improve animal welfare in varying environmental and managemental conditions Cows are naturally motivated to carry out certain activities such as grazing and rumination throughout 24 h forming repetitive patterns. These activities are predominant in pasture-based grazing cows and they spend 90% to 95% of their daily time grazing, ruminating, and resting . Cows doIn New Zealand, dairy cow production mainly relies on the grazing of pasture, and cows only receive supplementary feeds if required. New Zealand dairy herds are mainly populated with Holstein-Friesian, Jersey, and KiwiCross (Crossbreed of Holstein-Friesian/Jersey) breeds. Climatic conditions and weather in New Zealand are variable and exhibit a four-season pattern. Under these temperate free-range conditions, grazing cows generally exhibit a daily frequency of three to five grazing events . The freHow grazing dairy cows distribute their behaviors patterns over 24 h and how the frequency of behavior varies in different cow breeds and lactation groups during different seasons consuming different supplementary feeds is important in understanding their grazing process. Understanding the behavior patterns and time budgets, and their variations is an essential tool to improve the overall grazing management strategies for a pasture-based system. For example, the information can be applied to manage pasture allowance and additional feed resources for day-to-day and even within-a-day operations of the dairy farm throughout the year. Furthermore, the temporal distribution, duration, and intensity of grazing events can also help improve the nutrient supply to grazing cows. The behavior patterns represent benchmarked routines, and the time budgets indicate a net response of cows to their environment. Any prolonged deviations in those patterns or time budgets due to environmental and/or management constraints can result in negative consequences for animal productivity and health . DetermiThere is little literature concerning an intriguing question; how to describe the varying behavior patterns in grazing dairy cows and what happens at the individual animal level in the paddock. To the best of our knowledge, there are few studies in the literature to date that have explored the behavior patterns and time budgets in grazing dairy cows . WhereasThe primary objective of this study was to evaluate the variations in the 24-h behavior patterns and time budgets of grazing, rumination and idling in grazing dairy cows from different breeds and in different lactations, during different seasons, and when fed with different supplements.The study was carried out at Dairy unit 1, Massey University, Palmerston North, New Zealand . Approval (Protocol No. 18/58) for the care and handling protocols of animals was received from the Animal Ethics Committee, Massey University, New Zealand.Dairy unit 1 is a pasture-based dairy farm operated through a rotational grazing method with once-a-day milking (0500 hours) and spring calving systems. The farm area consists of 142.7 hectares, further divided into 63 grazing paddocks. The local climate is the temperate type with four seasons. The climatic seasons are classified as spring (September to November), summer (December to February), autumn (March to May), and winter (June to August). The average temperature of the local area was ~14 °C, and rainfall was ~970 mm with 1735 annual sunshine hours and 81% mean relative humidity over the data collection period . The dayN = 54) used in the study were a subset of the whole herd (N = ~260), they grazed together along with the other cows and altogether managed as one herd. The selection of cows was based on their breed type and lactation number within each breed and breeding worth (BW) index value. BW index value is the measure of the genetic merit of the animal for farm profit (N =18) cows from each of the three breeds, Holstein-Friesian, Jersey, and Holstein-Friesian/Jersey Crossbreed (KiwiCross) were included in the group. The cows included in each breed group were from different lactations  with six cows (N = 6) from each lactation. The cows within each lactation had varying BW index values (103 < BW > 151). The cows were altogether kept in the same grazing paddocks all the time throughout their lactation period (~270 d) except when brought to the milking shed (~ 2 h per milking) at 0500 hours. All cows from different breeds and in different lactations grazed the same pasture at the same time.Spring calved, pasture grazing lactating dairy cows (m profit . EighteeLolium perenne) mixed with red clover (Trifolium pretense) and white clover (Trifolium repens). Besides pasture, cows grazed chicory (Cichorium intybus) in spring. To meet energy requirements and to cope with the seasonal changes in pasture quality and production (Zea mays) and turnips (Brassica rapa) on various days during the summer and autumn seasons along with main feed (pasture). Supplementary feeds are used when quality pasture is less available, to fill the feed deficits and to support the cows to maintain energy intake and production  was used in this study to monitor and record the time spent grazing and ruminating by the grazing dairy cows over the lactation period. The device has been validated for measuring grazing and rumination behaviors in grazing dairy cows . The devThis study collected grazing (min/h) and rumination (min/h) behaviors of grazing dairy cows over the lactation period (~270 d). The lactation period of dairy cows ranged from August to April of the next year (2018–2019) following the typical spring calving system in New Zealand. The AfiCollar device was fitted to the individual cow after the calving event, and it was kept by the cow throughout the lactation period until drying off. The data collection started once the cow calved and ended when the cow was dried off. Minutes per hour spent grazing and rumination by the individual cow were collected for each hour of the day throughout the lactation period, organized, and used as such to perform analysis. The data for the individual animal were separately sorted in Microsoft Excel spreadsheets (Version 2016). The behavior data collected for the individual cow for the individual hour over 24 h were further classified and sorted by breed and lactation of the cow, the season of the year, each day within the season, and supplementary feeding within the season. The overall number of observations registered and used for analysis was 269314.Prior to the analysis, idling behavior was added as a new variable in the data and defined as the time when the animal was neither grazing nor ruminating . Idling A repeated measure design using PROC MIXED was performed in SAS  fitted with breed × lactation (with three levels each), individual cow within the breed and lactation, the hour of the day, season, the day within the season, and supplementary feeding within the season. The model investigated the differences in grazing (min/h), rumination (min/h), and idling behaviors (min/h) as recently done by another study . GrazingP-values by the same model. The time budget values were summarized and expressed as hours per day as the proportion (%) of the time within 24 h utilized for each behavior.The outputs by the same model, with the effects of breed, lactation, season, and supplementary feed for the whole dataset (without hour category) were used to determine behavior time budgets. The least square means of grazing, rumination, and idling across 24 h were considered as the average time budget for each behavior within 24 h. The means of time budgets for the breed, lactation, season, and supplementary feed within the season for grazing, rumination, and idling behaviors were compared using Hour of the day had a significant effect on the hourly grazing and rumination patterns of grazing dairy cows . The 24-The breed effect was not significant for both grazing and rumination; however, the breed had a statistical interaction with the hour of the day . The houThe lactation effect was not significant for both grazing and rumination, however, lactation had a statistical interaction with the hour of the day . The houSeason effect was significant for both grazing and rumination, and season had a statistical interaction with the hour of the day . The houSupplementary feed had a significant effect on both grazing and rumination, and feed had a statistical interaction with the hour of the day . The houGrazing, rumination, and idling time budgets for 24 h mainly varied due to the effects of season and feed within the season, however, the effects of breed and lactation remind nonsignificant . IrrespeThe 24 h time budgets of grazing dairy cows for grazing, rumination, and idling significantly varied during different seasons . Cows spThis study examined the trends and variations in the temporal patterns of grazing and rumination, and idling behaviors and their time budgets over 24 h in grazing dairy cows. The study was unique as it used a large behavior data set collected longitudinally over the whole lactation period. Grazing and rumination behaviors were continuously measured using an automated collar device (AfiCollar). All cows of different breeds and in lactations were kept as one herd in the same paddock and grazed the same pasture; therefore, the herding instinct of cattle may have influenced the differences in behaviors among breeds and lactation. Similarly, season and supplementary feeding were linked with each other in a way that supplementary feed was confounded within the season. Therefore, the confounding may have partly influenced the effects of season and supplementary feeds.Results indicated that regardless of breed type, lactation number, season, and supplementary feeds, pasture-grazing dairy cows spent most of the daylight hours grazing and most of the night hours ruminating; there was a short-lived grazing peak around midnight. The grazing intensity was highest in the morning after milking and, in the evening, before the start of the dark period. Previous studies have reported similar findings where most of the grazing activity occurred immediately following the milking and remained high throughout the day with a smaller peak around midnight . The higRumination is a natural behavior of cattle and the most important activity in the ruminants after grazing . The disHolstein-Friesian, Jersey, and KiwiCross breeds showed a similar distribution of grazing and ruminating patterns over 24 h. It has been reported that when grazing, cattle often synchronize their behavior in a way that animals as a group feed, ruminate, and rest at the same time . The synThe overall temporal patterns of grazing and rumination over 24 h were similar between grazing dairy cows in different lactations. However, the continuous and more intense grazing activity during daylight hours by first lactation cows can be justified as they have a smaller body size, take smaller bites, and eat slower, hence graze longer compared to mature cows to address their nutritional demands. Furthermore, first-lactation cows are still in a growing phase and need additional energy to support growth in addition to energy for maintenance requirements .The current study found variations in the onset and cessation of grazing activity for varying day lengths during different seasons. Grazing activity occurred mainly in daylight during different times of the year, but the day length affected changes in the grazing patterns. This might be a consequence of the interaction of photoperiod and environmental temperatures. Seasonal variations in photoperiod affect grazing behavior and resultant herbage intake . CompareThe cows mainly grazed pasture; however, different supplements were fed to the cows in different seasons at different times of day to address the feed demands. Time of day and feed type are confounded and their effects on each other cannot be separated. Therefore, the time of day when the supplement is fed would likely have the greater impact on grazing behavior rather than the supplement itself in the current study. Variations in the temporal distributions of grazing and rumination patterns were also linked with the different supplementary feeds consumed by animals during different seasons. The variations in grazing and rumination activities were high when animals consumed supplements along with pasture. Supplement and silage were usually fed to cows in summer as additional feeds to fulfill their energy demands as pasture quality was low at that time. Although the days were longer in summer, the cows finished their grazing activity earlier in the evening and started ruminating. It has already been reported that quantity, quality, and the timing of feeding supplements greatly influence behavior patterns of pasture-grazing cows . It has Time budgets for grazing, rumination, and idling activities over 24 h were quite similar between cows from different breed groups and cows in different lactations. However, the proportion of time spent chewing (grazing plus rumination) over 24 h decreased and the amount of time spent idling increased in the cows with consecutive higher lactation numbers. A recent report that cows in higher lactations spend more time lying compared to cows in early lactations . AnotherSeasonal variations in 24 h time budgets in grazing dairy cows were prominent. The percentage of time spent chewing increased from spring  reached the peak at the end of spring and started declining in summer. The chewing time budget was further down and lowest in autumn when animals were ready to be dried off and received supplement feeds; whereas the proportion of time spent idling was just the opposite of chewing. Variations in behavior time budgets were apparent in the autumn season when cows were about to be dried off, and during the time cows received supplements; this resulted in a higher amount of time spent idling. The amount of time spent idling was highest in autumn when most of the animals were about to be dried off and had less feed requirements, and the cows received supplement feeds as well. A recent study  reportedThe time budgets for grazing and rumination did not vary when animals were fed on pasture, chicory, or silage, although, idling time was higher when animals consumed chicory, silage, and supplements. In a previous report, compared with perennial ryegrass, as the dietary proportion of chicory increased, cows spent more time idling and less time ruminating and increased ingestive mastications five and three times for chicory, respectively . VariatiGrazing dairy cows spend most of the daytime grazing to maximize energy intake and most of the nighttime ruminating the grazed herbage. Grazing activity appears to be high at dawn and at dusk with the latter being more intense. Grazing and ruminating patterns are not different between different breed groups although, Jersey cows spend a relatively long time grazing and Holstein-Friesian cows spend a longer time ruminating. Cows in the first lactation graze continuously with fewer resting intervals compared with those in higher lactations. Time of the day and seasonal variations suggested that grazing cows can adjust their behavior patterns according to day lengths. The diurnal changes in herbage quality might also be playing a role in driving the behavior patterns that need further exploration. Cows spend less time grazing and ultimately less time ruminating when pasture has been supplemented with additional feeds. Most of the time over 24 h is spent grazing followed by ruminating and idling in dairy cows in a pasture-based system. Time budgets for the behavior activities over 24 h do not vary much between breed or lactation groups. Whereas variations in time budgets are observed during different seasons and for different supplementary feeds. The analysis of daily behavior patterns can be helpful in support to predict and addressing the behavioral needs of different animals in different climatic conditions by molding the management practices according to the daily behavioral needs. Thus, using the temporal distribution in management strategies to drive the 24 h supply of nutrients can be a potential tool in grazing management.skad038_suppl_Supplementary_TablesClick here for additional data file.


Head and neck cancers (HNCs) are one of the commonest cancers in low- and middle-income countries. There is a paucity of data on comorbid psychiatric problems associated with HNCs. The present study is aimed at reporting the pattern of psychiatric caseness in HNC patients who were referred to specialist psycho-oncology service and also investigate the predictors of psychiatric caseness in oral cancer patients.Case records of all patients with HNC referred to an integrated psycho-oncology service over 7 years (October 2011–December 2018) from a cancer hospital were analysed. All patients were assessed by a trained consultant psychiatrist and ICD-10 diagnoses were ascertained based on a clinical interview with the patients and family members. Associations of psychiatric caseness for consecutive oral cancer patients assessed by the psycho-oncology services over 2 years (January 2017–December 2018) were calculated by using univariate and multivariate statistical methods. Simple descriptive statistics of the referred patients were conducted, followed by logistic regression to find the associations of psychiatric caseness in oral cancer patients.p = 0.04); having worries about having pain in the post-operative period ; worries about implications of the cancer and its treatment on the family ; and longer duration of hospital stay period  were independently associated with psychiatric caseness even after controlling for confounders.The psycho-oncology service assessed 771 HNC patients over 7 years. The commonest referrals were patients with oral cancer . For the years 2017–2018, 179 consecutive oral cancer patients were evaluated by the psycho-oncology service. Multivariate logistic regression analysis showed that being a woman (OR = 2.33; 95% CI = 1.02–5.32; Specialist psycho-oncology services are important in the management of oral cancer patients and in addressing the mental health needs of this very vulnerable group of patients. A combination of psychoeducation, pragmatic psychological interventions and medications were used to treat these patients. In 2020, the Global Cancer Observatory database estimated that cancers of the head and neck region constitute the second most common cancers in India . It has Head and neck surgeries interfere with the motor functions, like speech, chewing and swallowing; sensory functions, like taste and smell; and social functions, like communication and expression of interest. As disfigurement due to HNC surgeries is often visible, HNCs are known to be associated with poor self-esteem, poorer self-confidence and body image difficulties when compared to less visible cancers . YoungerHNC is associated with the higher prevalence of psychological distress, even 7–11 years after treatment , 17. ManThe aim of the present study was to report real-life data on psychiatric morbidities of HNC patients based on a 7-year long experience of providing psycho-oncology services to HNC patients in a tertiary cancer centre. The current practice in the study centre is to conduct preoperative psychiatric assessment for patients planned for HNC surgeries. The goal of this assessment is to prepare the patients for the upcoming surgery and to address their concerns so that they are less apprehensive and can cope with the treatment process better. Previous research has reported that two-thirds of the patients have reported in studies that preoperative counselling has been helpful , 23. PreThe scope and need of psycho-oncology services have also grown exponentially. This study examines the peri-operative psychiatric morbidities of HNC patients with a special emphasis on oral cancer from a specialist cancer centre in eastern India. Recent research on the journey of cancer patients from India has elicited complexities in the access to cancer care, emphasised the psychological journey of patients, highlighted stigma of being a cancer patient, impact of decision-making on adherence to treatment and the economic impact of cancer care alongside the modifiers to accessing cancer care .The first objective of the present study was to explore and describe the pattern of psychiatric morbidities in HNC patients in a specialist cancer centre. The second objective was to study the associations of psychiatric morbidities in the peri-operative period for oral cancer.The study was conducted in a not-for-profit cancer centre in eastern India, Tata Medical Center, Kolkata, which currently has 450 beds and state-of-the-art cancer treatment facilities. The hospital caters mainly to patients from the East Indian states of West Bengal, Jharkhand, Bihar, Assam, Sikkim, Meghalaya, Mizoram and neighbouring countries, like Bangladesh, Nepal and Bhutan. The hospital has a psycho-oncology service, established in the very first year of its inception, led by consultant psychiatrists and psychologists. The psycho-oncology department has daily out-patient services and in-patient services, both led by the two consultant psychiatrists. Most patients referred to psycho-oncology are seen on the same day of referral.HNC patients were frequently referred to the department of psycho-oncology as an out-patient prior to surgery and again in the post-operative period. Patients were assessed on the same day of referral as per the existing protocol by one of the consultant psychiatrists of the department. The department of psychology, since its inception in 2011, has had a paperless documentation practice. All clinical notes were contemporaneously recorded in the electronic health records. At the end of 2016, there was a change made for the shared care protocol for patients with oral cancer as this was the commonest HNC needing psychiatric inputs. Since January 2017, all patients with oral cancers were prospectively evaluated by one of the two consultant psychiatrists during the preoperative period. Alongside a standard psychiatric assessment, the preoperative oral cancer patients were screened for the four most common psychological worries: a) worries related to the possibility of experiencing pain in the post-operative period; b) worries related to future body image problems secondary to facial disfigurement; c) worries related to direct and indirect costs of cancer care impacting finances of the family; and d) worries related to the cancer treatment disrupting family life. The psychiatric diagnosis reported in this study had taken into consideration both the preoperative psychiatric assessment and the post-operative assessment. The oral cancer patients were also referred to the psycho-oncology service in the immediate post-operative period for continuity of psychiatric care and for providing psychological support as and when appropriate. A separate contemporaneous database for oral cancer patients was started to aid in better clinical communication that was maintained by the clinical psycho-oncology fellows of the department.Data for all HNC patients who had been evaluated by the department of psycho-oncology between 2011 and 2018 were examined for the purposes of this study. The records included the basic demographic details of the patient, the type and stage of cancer, medical comorbidities of the patient, type of surgery undertaken, details of the psychiatric assessment by a consultant psychiatrist, psychiatric diagnosis, if any, for the patient and the nature of interventions undertaken by the psycho-oncology service. Additionally, for the years 2017–2018, data for all oral cancer patients were maintained in the psycho-oncology departmental database. Data were entered on a predetermined proforma. In view of the retrospective nature of the study, waiver of consent was obtained from the institutional ethics committee as per institutional policy (IEC Protocol Waiver No – EC/WV/TMC/012/19).t-test for continuous variables. Multivariate logistic regression analysis was carried out for patients with oral cancer, using the dichotomous variable of psychiatric caseness as the intendant variable and other variables as predictor variables that were significant in univariate analysis.The data were analysed using Statistical Package for the Social Sciences 25. Univariate analysis included chi-squared test for categorical variables and Over the period of the study, the Department of Psycho-oncology had evaluated 771 HNC patients . Majoritp = 0.04); having worries about experiencing pain in the post-operative period ; worries about implications of the cancer and its treatment on the family ; and longer duration of hospital stay  were independently associated with psychiatric caseness even after controlling for confounders. Surprisingly, worries about potential body image and deformity was not associated with psychiatric caseness.Since 2017–2018, all patients with oral cancer were assessed preoperatively by one of the consultant psychiatrists who led the psycho- oncology service. The commonest cancers within the oral cavity  includedSurgeries for oral cancer are often associated with significant disfigurement, physical and emotional pain and resultant emotional distress. The present study on psychiatric morbidity in patients with oral cancer showed that being a woman, having preoperative worries about pain, having preoperative worries about impact of the cancer treatment on the family and longer duration of hospital stay were independently associated with psychiatric diagnosis in the peri-operative period. The strengths of the present study include a relatively large sample size, evaluation being conducted by a trained consultant psychiatrist with special interest in psycho-oncology and the study being set in the LMIC that contributes the greatest number of HNC patients globally. Having a dedicated psycho-oncology service working closely with HNC services and having a standardised preoperative psychiatric evaluation protocol for HNC patients made the assessments uniform. The weaknesses of the study were a) the cross-sectional nature of the study and b) being conducted in a single centre.The present study on oral cancer patients showed that being a woman was associated with psychiatric morbidity. This follows a similar trend around the world , 26 and Body image is a subjective perception about one’s own appearance, and is often modified by the reactions elicited from others . People Our study found longer hospital stay was associated with increased psychiatric problems as reported by studies from other parts of the world . ProlongThe role of psycho-oncology services is extremely valuable in HNCs. Preoperative evaluation of anxiety and common worries, preparedness for treatment, social stressors, personality factors, coping resources and pre-existing psychiatric morbidities can help the treating team to assess the presence of or anticipate risk of psychological morbidity in a patient. It can provide valuable clinical information about the patient’s coping ability. Unaddressed psychiatric morbidities may interfere with the ability of the patient to engage with oncology services. This study reports the findings of the preoperative psychiatric evaluation for people with oral cancers. The common interventions undertaken by the psycho-oncology service included a mental health assessment of the patient in the context of the medical condition, planning appropriate psychiatric care and coordinating with the surgical service and the intensive care unit. The profile of a typical HNC patient who qualifies for various psychiatric diagnoses, reasons for referrals, goals of mental health care in the peri-operative period and interventions offered are summarised for the reader in HNCs are one of the commonest cancers in LMICs and require multidisciplinary care. Psychiatric comorbidities are common and are best managed when referred to a specialist psycho-oncology service early on. The various mental health conditions may require specialist mental health inputs and are best managed jointly with HNC surgical oncologists. There is very little systematic data on this group from LMICs and further research is required in the future.The authors declare that they do not have any conflicts of interest.The work was not supported by any external funding.


Gynecological ultrasonography plays a central role in the management of endometriosis. The rapid technical development as well as the currently increasing evidence for non-invasive diagnostic methods require an updated compilation of recommendations for the use of ultrasound in the management of endometriosis. The present work aims to highlight the accuracy of sonography for diagnosing and classifying endometriosis and will formulate the present list of key messages and recommendations. This paper aims to demonstrate the accuracy of TVS in the diagnosis and classification of endometriosis and to discuss the clinical applications and consequences of TVS findings for indication, surgical planning and assessment of associated risk factors. (1) Sophisticated ultrasound is the primary imaging modality recommended for suspected endometriosis. The examination procedure should be performed according to the IDEA Consensus. (2) Surgical intervention to confirm the diagnosis alone is not recommended. A preoperative imaging procedure with TVS and/or MRI is strongly recommended. (3) Ultrasound examination does not allow the definitive exclusion of endometriosis. (4) The examination is primarily transvaginal and should always be combined with a speculum and a bimanual examination. (5) Additional transabdominal ultrasonography may enhance the accuracy of the examination in case of extra pelvic disease, extensive findings or limited transvaginal access. (6) Sonographic assessment of both kidneys is mandatory when deep endometriosis (DE) and endometrioma are suspected. (7) Endometriomas are well defined by sonographic criteria. When evaluating the ovaries, the use of IOTA criteria is recommended. (8) The description of sonographic findings of deep endometriosis should be systematically recorded and performed using IDEA terminology. (9) Adenomyosis uteri has sonographically well-defined criteria (MUSA) that allow for detection with high sensitivity and specificity. MRI is not superior to differentiated skilled ultrasonography. (10) Classification of the extent of findings should be done according to the #Enzian classification. The current data situation proves the best possible prediction of the intraoperative situs of endometriosis (exclusive peritoneum) for the non-invasive application of the #Enzian classification. (11) Transvaginal sonographic examination by an experienced examiner is not inferior to MRI diagnostics regarding sensitivity and specificity in the prediction of the extent of deep endometriosis. (12) The major advantage of non-invasive imaging and classification of endometriosis is the differentiated planning or possible avoidance of surgical interventions. The recommendations represent the opinion of experts in the field of non-invasive and invasive diagnostics as well as therapy of endometriosis. They were developed with the participation of the following national and international societies: DEGUM, ÖGUM, SGUM, SEF, AGEM/DGGG, and EEL. First described in 1860 –5. In adThis IDEA Consensus is the most widely used and accepted standard for the sonographic examination procedure in patients with endometriosis .Although surgery is still considered the diagnostic gold standard, especially in patients with the peritoneal disease, this dogmatic approach brings three major problems that need to be discussed. First and foremost, surgical and subsequent histologic diagnosis is again based on the surgeon’s visualization of endometriosis. Extensive adhesions and deep endometriosis (DE), some of which may be extraperitoneal, may primarily obscure the extent of the disease. Dissection of the occluded spaces requires experience and advanced surgical skills of the surgeon to meet the requirements of a “gold standard test.” As a result, patients with severe adhesions or a so-called “frozen pelvis” may underestimate the true extent of endometriosis. Especially in patients with minor symptoms, the indication for surgery and in particular the extent of the procedure must be weighed against the potential risks . Second,“…advances in the quality and availability of imaging modalities for at least some forms of endometriosis on the one hand and the operative risk, limited access to highly qualified surgeons and financial implications on the other, calls for the urgent need for a refinement of this dogma [, and delete the diagnostic laparoscopy as recommended gold standard in the diagnosis of endometriosis, when imaging finding shows changes suspected of endometriosis”.Third, uterine adenomyosis cannot always be confirmed visually or even histologically in patients with fertility problems, which may lead to a diagnostic dilemma regarding the laparoscopic “gold standard test.” As a consequence, the eminent European Society for Human Reproduction (ESHRE) states in the updated and probably most extensive and most cited endometriosis guideline regarding laparoscopic identification of endometriosis as a gold standard test that is dogma , and delDiagnostic imaging methods include multiple modalities such as MRI, computed tomography (CT), X-ray and sonography. Regarding the non-invasive diagnosis of endometriosis, only MRI and sonography in form of TVS have been proven reliable and accurate tools for diagnosing the disease , 16.A Cochrane Review concerning the imaging modalities for endometriosis concludes that TVS and MRI help surgeons to better plan an operative procedure . HoweverThe different accuracy of sonographic diagnostics is mainly influenced by the size and localization of the findings and the accessibility with the ultrasound probe, but also by the skill and experience of the examiner. Learning the technique requires a certain number of examinations, as Tammaa  demonstrThe present work should contribute as a basis for the establishment of standardized sonographic diagnostics of endometriosis, which in the future should affect the standards of training and required quality of diagnostics.TVS has proven to be a cost-effective, easy-at-hand tool showing real-time assessment of the uterus, the pouch of Douglas, and ovaries. In addition, the visualization and assessment of the ureters, urinary bladder, and rectum facilitate the diagnosis of anatomical changes due to endometriosis. Compared to bimanual examination, several papers have shown the diagnostic superiority of TVS. However, especially in patients with vaginal lesions, the combination of imaging techniques and clinical examination, including speculum examination and bimanual palpation, leads to a clearer view of the structures involved –23. In aHigher resolution and anatomical proximity are key advantages of TVS for a pelvic examination, but in cases with the severe extent of DE, lesions can exceed beyond the pelvic region  group published a consensus statement in 2016 . As the The high diagnostic accuracy of TVS for diagnosing DE is well documented. In their Cochrane review, Nisenblat et al.  report aglobally enlarged uterusasymmetry between the anterior and posterior wall of the uterusirregular and/or ill-defined lesions without rimfan-shaped shadowingnon-uniform, mixed echogenicity with cysts, hyperechogenic islands and/or sub-endometrial lines and budsin Doppler sonography depiction of a translesional flowthe junctional zone is often thickened, irregular or ill-defineddepictable interruption of the junctional zoneAdenomyosis uteri is defined as the presence of ectopic, non-neoplastic endometrial glands and stroma within the myometrium. As a rule, the ectopic endometrium is surrounded by hypertrophic and hyperplastic myometrium. In severe cases, the entire structure of the myometrium, i.e., the architecture of the uterine wall, is completely destroyed. Especially young patients with adenomyosis uteri frequently suffer from pain and dysmenorrhea. Furthermore, adenomyosis uteri affects the reproductive outcome and leads to pregnancy and obstetrical complications . TherefoUsually, not all the above criteria are met at the same time Figs. , 12. TheThe accurate documentation can be done individually (description) or in a standardized form, e.g., by a uniform classification. This is of great advantage both for the rapid assessment of the findings and for interdisciplinary communication.The ideal system for classifying endometriosis should be applicable for imaging and surgical interventions. Although several scores and systems have been proposed over the past 50 years , the maiThe rASRM classification, which has been in use over decades, primarily focuses on the effects of endometriosis on fertility in association with peritoneal and ovarian disease and secondary adhesions. This excludes the detailed description of DE which is considered the main disadvantage of this score , 47. NevTo overcome the lack of adequately describing DE, the Enzian classification was developed in 2003 , 49 and Recently, a prospective, multicentre study including 745 patients undergoing TVS in combination with the #Enzian classification and surgery  documentTherefore, the ISGE recommends the best possible detection of endometriosis using the systematic IDEA criteria and the comprehensive classification by the #Enzian classification .Several meta-analyses confirmed the equivalence of TVS and MRI in the diagnosis of the specific pelvic anatomic location of endometriosis lesions , 55, 56.The risk factors for surgical complexity and postoperative complications after more or less radical colorectal surgery in DE are well known. The lesion's location and size significantly impact this , 61. ForThe risk for surgical complications correlates with the extent of lesions and, therefore, with a higher Enzian/#Enzian score in certain anatomic compartments. For example, Poupon et al. developed a nomogram classification  showing Therefore, the use of TVS for non-invasive assessment of surgical complexity and risk factors for surgical complications is recommended.The use of TVS is an efficient and accurate tool for the non-invasive diagnosis of endometriosis. Although this imaging technique does have limitations such as operator dependency, it is cost-effective and enables the clinician to establish a diagnosis in cases of the ovarian and deep disease. Many doctors still rely on surgical and histological confirmation as a gold standard test. This approach is highly questionable and may not be up to date. The authors advocate for using of TVS as a primary tool to evaluate women with suspected endometriosis and to stratify these patients into low- and high-risk patients based on the results of TVS-based preoperative assessment. A nearly complete non-invasive diagnosis of endometriosis opens up new perspectives for conservative and surgical treatment. Using the #Enzian classification, also in the context of sonographic assessment, provides clinicians with a uniform “language” for a comprehensive and easily reproducible description of endometriosis.