On a global scale, cases of placenta accreta spectrum are often just identified during cesarean delivery because they are missed during antenatal care screening. Routine operating teams not trained in the management of placenta accreta spectrum are faced with difficult surgical situations and have to make decisions that may define the clinical outcomes. Although there are general recommendations for the intraoperative management of placenta accreta spectrum, no studies have described the clinical reality of unexpected placenta accreta spectrum cases in resource-poor settings.This study aimed to describe the maternal outcomes of previously undiagnosed placenta accreta spectrum managed in resource-poor settings in Colombia and Indonesia.This was a retrospective case series of women with histologically confirmed placenta accreta spectrum treated in 2 placenta accreta spectrum centers after referral from remote resource-poor hospitals. Clinical outcomes were analyzed according to the initial type of management: (1) no cesarean delivery; (2) placenta left in situ after cesarean delivery; (3) partial removal of the placenta after cesarean delivery; and (4) post–cesarean hysterectomy. In addition, we evaluated the use of telemedicine by comparing the outcomes of women in hospitals that used the support of the placenta accreta spectrum center during the initial surgery.A total of 29 women who were initially managed in Colombia (n=2) and Indonesia (n=27) were included. The lowest volume of blood loss and the lowest frequency of complications were in women who underwent deferred cesarean delivery  and in those who had a delayed placental delivery . Five maternal deaths (14%) occurred in the group that did not receive telehelp, and 4 women died of irreversible shock because of uncontrolled bleeding.Previously undiagnosed placenta accreta spectrum in resource-poor hospitals was associated with a high risk of maternal mortality. Open–close abdominal surgery or leaving the placenta in situ seem to be the best choices for unexpected placenta accreta spectrum management in resource-poor settings. Telemedicine with a placenta accreta spectrum center may improve prognosis. This study was conducted to describe maternal outcomes of unexpected placenta accreta spectrum (PAS) intraoperatively in resource-poor settings.For the management of unexpected PAS in resource-poor hospitals, better outcomes were reported in cases where further abdominal surgery was abandoned and the woman referred, or the placenta was left in situ, compared with cases where attempts to remove the placenta or hysterectomy were undertaken. Intraoperative telehelp may provide intraoperative strategies to reduce complications during management of PAS in resource-poor settings.This study confirms the high burden of mortality in women with PAS in resource-poor settings. Intraoperative management strategies are needed for cases with unexpected PAS, and this study described maternal outcomes regarding several surgical strategies, and the importance of intraoperative telehelp, which can be used to provide PAS management recommendations for resource-poor hospitals.Placenta accreta spectrum (PAS) is one of the most frightening obstetrical emergencies, mostly leading to massive blood loss with major morbidity and even mortality.The complex situation of too many and, at the same time, too few cesarean deliveries (CDs) is especially valid in many low- and middle-income countries (LMIC): the number of CDs is rising,,Management guidelines are applicable to these PAS centers,We have set up PAS referral centers in Colombia and Indonesia, and a care regionalization program for women with PAS has been implemented since 2016. Interdisciplinary groups in charge of managing PAS (PAS teams) have established contact with hospitals in the region, offering advisory services on the diagnosis and treatment of PAS that meet the criteria applied in centers of excellence for PAS.This interaction also facilitates the transfer of women between hospitals and includes support during the initial management of emergent cases, as well as feedback to remote hospitals on the clinical outcomes of women transferred for surgery in the PAS centers.This study aimed to investigate the maternal outcomes of unexpected PAS initially managed in a resource-poor hospital and referred to our PAS referral centers.,,This retrospective descriptive study included women with histologically confirmed PASThe intraoperative suspicion of PAS in the resource-poor hospital was based on surgical reports that had to mention at least 1 of the following items: (1) bluish appearance with neovascularization on the uterine surface, (2) placental tissue invading the uterine wall with neovascularization, and/or (3) difficult partial delivery of the placenta. The intraoperative confirmation in the PAS center was based on the guidelines of the International Society for Placenta Accreta SpectrumFor the analysis, women were divided according to the type of management in the initial hospital: (1) no CD and referral ; (2) placenta left in situ after birth of the child and referral; (3) partial removal of the placenta after birth of the child and referral; and (4) referral after cesarean hysterectomy.In addition, we evaluated the use of telehelp by comparing the outcomes of women in hospitals that used the support of the PAS center through telemedicine during the initial surgery.The level of maternal care in the referral hospital was defined as basic  or medium .Previous blood loss was estimated by combining the measured blood loss in the suction machine with visual assessment by the previous surgeon and anesthesiologist in the initial hospital. Blood loss in the referral hospital was measured by collecting blood suction and gauze weights during surgery.Intraoperative telehelp cases were defined as cases where the surgeon was seeking a second opinion from the PAS center to make clinical decisions during surgery in a resource-poor hospital.Telehelp varied from confirmation of the clinical suspicion of intraoperative PAS to advice on surgical technique. The use of telehelp included phone calls, sending intraoperative photos, and video calls to provide intraoperative suggestions or surgical strategies to avoid unnecessary bleeding or organ damage. The advice given included instructions on open–close procedures, leaving the placenta in situ, avoiding dangerous maneuvers such as placental traction, performing bladder dissection, and placing multiple stitches in the colpouterine area to reduce the intraoperative bleeding. We dichotomized the use of telehelp and did not qualify it further.,Women who arrived at the PAS center in a stable condition underwent abdominal ultrasonography to analyze topography and placental invasion. PAS management was dependent on the severity and location of placental invasion.In life-threatening situations, such as heavy vaginal bleeding and/or hemodynamic instability, emergency surgery was immediately performed with aortic clamping to reduce blood loss and simultaneous resuscitation, followed by intraoperative staging and surgical management, depending on the topography of the invasion and secondary bleeding control.Clinical and epidemiologic information was obtained from medical and laboratory records and from the PAS database of both PAS centers. The results of the histologic studies of the hysterectomy cases performed in hospitals with poor resources were collected.Continuous variables were expressed as central tendency measurements (mean and median) and dispersion measurements (standard deviation or interquartile range) based on normal distribution criteria. Categorical variables were expressed as absolute and relative frequencies. The findings were reported according to the STROBE  guidelines .The study was registered under numbers 1711-2019 and 016-2022, respectively, and approved by the institutional review boards of the SGATH and CAP, and the boards of directors of the resource-poor hospitals. Informed consent was not required because the rules defined in the Medical Research Involving Human Subjects Act did not apply to this study. Participants were not subject to procedures and were not required to follow rules of behavior. This study complied with the principles of the Declaration of Helsinki.Thirty-six cases met the inclusion criteria, and 7 were excluded from the data analysis because of incomplete data, resulting in 29 cases for the analyses.1.In 5 women, the laparotomy wound was closed after the intraoperative/clinical diagnosis of PAS was made (open–close laparotomy), and the women were referred to the PAS center.2.Six women underwent CD  and were referred to the PAS center.3.In 11 women, the surgeons attempted to remove the placenta after the birth of the child through lower uterine segment hysterotomy, cutting through the uterine wall and placental tissue. The surgeons attempted to control the bleeding as much as possible, closed the abdominal wall, and referred the women to the PAS center.4.In 7 cases, the surgeons attempted to remove the placenta after birth of the infant, after which a hysterectomy was performed, the abdominal wall was closed, and the patient was referred to the PAS center.From the 29 cases of unexpected PAS (27 from Indonesia and 2 from Colombia), 4 outcome groups were established on the basis of the initial management at the resource-poor hospital:Demographic data and maternal outcomes, according to the type of initial management, are presented in During antenatal care, 90% (n=26/29) of the women underwent ultrasound examination. Despite these ultrasounds, PAS remained undiagnosed until CD in all women.In 16 of 29 women (55%), a planned CD  was scheduled. Two women delivered infants who died of intrauterine fetal death before surgery.Women who had deferred CD had the best clinical results (lower volume of bleeding and frequency of complications) . Women wIntraoperative telehelp was performed in 7 cases: in 5 cases, an open–close procedure was recommended, and in 6 cases it was advised to leave the placenta in situ. This prevented massive bleeding and reduced the use of blood transfusions . Table 2There were 5 maternal deaths (17%); telehelp was not used in any of these cases. Four women (80%) died because of irreversible shock after uncontrollable bleeding following the initial surgery in a resource-poor hospital. In 1 woman, the placenta was left in situ, and she was referred to the PAS center 3 days after hospitalization. She arrived at the PAS center 2 days after being referred because of the difficulty in accessing transportation where the resource-poor hospital and tertiary center are located on different islands. The patient died of severe sepsis 6 days after the initial surgery.Our data showed that unexpected PAS could be life-threatening, especially in resource-poor settings; 14% of the women in this case series died of complications related to PAS. The clinical decisions of the surgeon in cases of unexpected PAS diagnosed during CD largely predict the clinical course of women. The worst decision was to attempt to remove the placenta in a setting without additional strategies to control bleeding .Lack of knowledge about the dangers of PAS is a major factor contributing to maternal mortality.,Obstetricians need to be instructed on what to do in unexpected PAS cases, and more importantly, they should know what interventions should be avoided.On the basis of the cases described in this series, not touching the placenta  is highly recommended to avoid massive bleeding during surgery at resource-poor hospitals.In some situations, it is impossible to refrain from CD . In such cases, the fetus should be delivered, preferably using fundal hysterotomy, while avoiding and not touching the placenta and subsequently closing the uterus and abdomen, to refer the women to a hospital with experience in the management of PAS.,Damaging the placenta or placental removal without proper vascular control can lead to a critical condition of massive bleedingIn some situations , it may not be possible to postpone a hysterectomy in women with intraoperatively diagnosed PAS. In such situations, advice can be obtained through telemedicine.Obstetricians caring for women with antenatal diagnosis of PAS should maximize the effort to preferably refer women to expert teams in a timely manner.Although all cases included in this study were initially managed in basic resource-poor hospitals, the intraoperative finding of PAS can also occur in normal- or high-resource or referral hospitals that may not have a PAS team or where the PAS team is not available immediately. In line with the expert opinion,The limitation of this study is bias inherent to the nature of the study design. This was a retrospective study, and therefore some information was not available; for example, we were unable to identify why telehelp was not used in some cases, whether there were other contributing factors, or how many women were not referred in the study time period. However, this is a large case series of women with PAS as an unexpected intraoperative finding. Our observations draw attention to a relatively frequent situation among women with PAS (late diagnosis during laparotomy), and it is necessary to carry out multicenter studies at the regional or national level to evaluate the clinical results of women with an intraoperative diagnosis of PAS and the feasibility and utility of telemedicine in those situations.Unexpected PAS at CD in resource-poor hospitals increases the risk of maternal mortality. Open–close abdominal surgery and leaving the placenta in situ are the preferred choices for undiagnosed PAS management in such settings. Telehelp with a PAS center may improve prognosis by distinguishing PAS intraoperatively and advising on surgical strategies to reduce maternal mortality and morbidity.


Diabetes mellitus is emerging as one of the major public health threats that contributed to 2% of all deaths in Tanzania in 2016. Although adequate knowledge related to diabetes mellitus is associated with early case detection, prevention, and minimization of health complications and socioeconomic-related consequences, there is less evidence about the adequacy of the community´s knowledge of diabetes in Tanzania. This study aimed to determine knowledge about diabetes mellitus and its associated factors among diabetic outpatients. A cross-sectional study was conducted among 220 diabetic outpatients aged 18 years and above at Muhimbili national hospital in Tanzania between February and April 2017. Data were collected using a structured pretested questionnaire and were entered into Microsoft Excel and exported to SPSS Version 20 for analysis. Bivariate and multivariate logistic regression was used to determine the predictive variables. The significance of independent variables was declared at a 95% confidence level and p-value < 0.05. A total of 137 (64.01%) of the participants had adequate knowledge about diabetes mellitus. The majority (86.9% and 85.1%) reported having adequate knowledge of complications of diabetes and treatment options for diabetes respectively. The least level of knowledge reported was on signs and symptoms (48.6%) and type of diabetes (32.7%). The majority (54%) cited health facilities as the most common sources of information related to diabetes. Both bivariate and multivariate logistic regression analyses showed that there was a statistical association between knowledge related to diabetes and the level of education of study participants. The overall level of knowledge of participants about diabetes mellitus was adequate, with a low level of knowledge related to signs and symptoms of diabetes, and type of diabetes. Health facilities were the most common sources of information related to diabetes. Policy and decision-makers and health care providers should take collective action to improve community knowledge about diabetes. Health education related to diabetes should be integrated into the educational curriculum at all levels in Tanzania, which would massively increase awareness of diabetes. Diabetes Mellitus is one of the serious and devastating chronic diseases of public health concern that affects the lives and well-being of individuals across the globe . The WorIn recognition of this challenge, the Government of Tanzanian through its Ministry of Health, Community Development, Gender, Elderly and Children (MoHCDGEC) developed a National Non-communicable Diseases Prevention and Control Strategy to ensure improved access, availability, and affordability of quality non-communicable services in the country . These eStudy design and setting: this was a descriptive cross-sectional study conducted among outpatients at the Muhimbili National Hospital diabetes clinic. The hospital is located in Dar es Salaam, the largest most commercial city in Tanzania. The hospital serves as a national referral hospital while simultaneously functioning as a teaching and research facility for the Muhimbili University of Health and Allied Sciences. It offers specialized care across the spectrum of clinical medicine. The hospital has both adult and pediatric diabetes clinics. The study was conducted between February and April 2017.Sampling and study population: the study enrolled a total of 220 outpatients from an estimation of 5760 diabetes outpatients´ attendance per year. Patients who attended the clinic within one month of data collection were consecutively included in the sample. Outpatients attending diabetes mellitus services aged 18 years or above were included in the study based on their consent. Enrolled study participants were either newly diagnosed diabetes patients or patients who were continuing with diabetes mellitus treatments. Patients with other illnesses besides diabetes mellitus were excluded from the study.Data collection methods and instruments: we used a semi-structured questionnaire to collect data from outpatients in the diabetes clinic at Muhimbili National Hospital. The development of the questionnaire was informed by relevant literature [terature -22. The Data quality control and assurance: the questionnaire was pretested among 25 outpatients at the Morogoro Regional Referral Hospital two weeks before the commencement of the actual study. The pre-testing aimed to check for the consistency, accuracy, and relevance of the questions. The questionnaire was revised based on the responses to the pretest. The analysis of the pre-tested data was excluded from the overall results of this study. The filled questionnaires were checked daily by the first author and reviewed by the second author weekly to ensure completeness and consistency. A double data entry technique was used.Variable measurement: the level of knowledge of diabetes mellitus was taken as the dependent variable. The independent variables include socio-demographic characteristics of participants .Data analysis: the collected data were entered into MS Excel to be checked and cleaned before being exported into SPSS version 20 for analysis. Descriptive statistics such as frequency and percentage were computed. A composite knowledge variable from knowledge questions  was created, assigning numbers 1 and 0 for adequate and inadequate knowledge respectively for each of the knowledge questions. Bivariate and multivariate logistic regression was used to determine the predictive variables. The significance of independent variables was declared at a 95% confidence level and p-value < 0.05.Ethical considerations: the protocol was reviewed and permission to collect data was granted by the leadership of Muhimbili Diabetic Clinic with reference MNH/TRC/Research/2017/014. Before data collection, every participant was informed about the nature, purpose, and procedures of the study. Participants were asked to sign the consent form for their acceptance to participate in the study. Participants were given the freedom to either answer specific questions or withdraw from the study at any time. To ensure anonymity, identity numbers rather than names were used to represent the study participants.Socio-demographic characteristics of study participants: a total of 214 out of 220 enrolled participants from the Muhimbili Diabetic Clinic participated in this study. The mean age was 37 years with equal gender distribution among the participants. More than three-quarters (84.6%) of participants were employed. Almost half of the participants had either a primary education (45.3%) or no formal education (7.5%), and the majority were married (53.7%). The majority (68.7%) of participants lived in Dar es Salaam and 66.8% had diabetes mellitus for more than five years  of the participants were knowledgeable about diabetes mellitus. The majority of study participants  had knowledge on complications of diabetes mellitus, followed by knowledge on treatment options for diabetes  and causatives of diabetes . The least level of knowledge was on signs and symptoms of diabetes mellitus  and type of diabetes mellitus   .Potential sources of information related to diabetes mellitus: health facilities were reported by the majority (54%) of study participants as the most common sources of information related to diabetes mellitus followed by social media (18%) (ia (18%) .Associations between knowledge related to diabetes mellitus and socio-demographic characteristics: both bivariate and multivariate logistic regression analyses showed that there was a statistical association between knowledge related to diabetes mellitus and socio-demographic characteristics. In bivariate logistic regression analysis, education (primary) ; education (post-primary)  showed an increased odds of knowledge for diabetes. In multivariate logistic regression analysis, education (primary) ; education (post-primary)  showed a decrease odd of knowledge for diabetes mellitus. However, there was no statistical association between age, sex, occupation, marital status, years lived with diabetes mellitus, and place of residence of participants with their knowledge related to diabetes mellitus  and those outside the city accessing diabetes mellitus at the hospital placed at the tertiary level of health service delivery in Tanzania. Second, the study was conducted in a hospital that attracts outpatients with a diversity of socio-demographic factors. Third, the questionnaire used was adapted from the previous literature, with slight modifications. However, the study findings should be interpreted with caution because the study was conducted in one hospital and therefore reliability and generalizability of the results could be limited.The study participants had adequate knowledge related to diabetes mellitus and demonstrated a high level of knowledge of the treatment and complications of diabetes mellitus. Less knowledge of the types, signs, and symptoms of diabetes appeared the most common challenge. Health facilities were the main sources of diabetes-related information. The present study showed that social media were not adequately utilized to access diabetes mellitus-related information. The level of education was significantly associated with knowledge related to diabetes. Results of this study highlighted the need for utilizing social media with well-designed content to increase knowledge about diabetes that might promote a healthy lifestyle. It is surprising in this study that participants were aware of complications of diabetes mellitus but less knowledgeable of signs and symptoms and types of diabetes mellitus. Therefore, a further qualitative study needs to be conducted to confirm this observation and the potential explanations.


The Grasp and Release Test (GRT) was originally developed to measure effectiveness of an implanted neuroprosthesis in people with tetraplegia. Its ease of use and lack of floor and ceiling effects culminated in recommendations for inclusion in a battery of tests to measure outcome following upper limb reconstructive surgery. However, the length of time taken to administer the GRT in a clinical setting, lack of instructions of accepted grasp patterns in the upper limb reconstructive surgery population and scoring procedures lead to differences in reporting outcomes using this measure. In order to ensure clinical utility for the upper limb reconstructive surgery population, revisions of the original test instructions have been made and are reported in this article. Further testing of the psychometric properties of the new measure are currently underway. Recommendations of outcome measures to assess upper limb reconstructive surgery interventions such as tendon transfer and/or nerve transfer procedures in individuals with tetraplegia have been well documented , 2. The The GRT is a non-instrumented, one-handed object manipulation test used to measure hand function in people with tetraplegia. The GRT was originally designed to measure effectiveness of an implanted neuroprosthesis , 5. The https://neuraloutcomes.com/product/grasp-and-release-test/). While the GRT has been used to report changes in grasp and release following upper limb reconstructive surgery [Until recently, GRT use has mostly been limited to centres previously involved in a multi-site trial to evaluate an implanted neuroprosthesis for hand function . Due to  surgery , 8, util surgery . If requ surgery . Mulcahe surgery . Peckham surgery . In cont surgery  and Wang surgery  reportedThe GRT includes six objects that participants are asked to grasp, move and release as many times as possible in 30 s. The six objects tested in the GRT are; peg, paperweight, fork, block, juice can and videotape/book Fig. .Fig. 1GrThe objects vary in size, weight and surface texture. The objects represent a range of difficulties that can measure differences in performance. The test has been designed to minimise effects of extraneous factors which may interfere with the performance of the hand, such as fatigue of the proximal musculature or instability of the trunk. Therefore, the test board is placed in front of the participant and biased towards the test hand as needed to minimise reaching effort. The test stipulates consistent equipment placement and test board location so that performance over time and across participants may be compared meaningfully. The objectives of the GRT are: (1) to determine if ability to acquire, grasp, move and release a series of objects ranging in size and weight changes; and (2) to determine ability to acquire, grasp, move and release objects changes as a result of an intervention or changes over time.The original test to assess neuroprosthetic hand function in a research setting consisted of a pre-test to determine success or failure in acquiring, moving and releasing the object (including practice), followed by a main test with three 30-s trials for each successful object in the pre-test. The number of completions and failures in the 30-s trials are recorded, with comparisons made between objects successfully acquired with the neuroprosthesis turned on and off (maximum of six). Changes were made to the GRT testing procedure to standardise administration and maximise clinical efficiency in measuring impacts of upper limb reconstructive surgeries.Clarification of accepted prehension patterns taking into account the variability of grasps produced by upper limb reconstructive surgery.Removal of specific pre-test but allowing practice of each object prior to testing.Elimination of random testing order for objects, and change to tasks being performed in the order of the scoring sheet.Reduction of testing trials for each object from three times down to once.Standardisation of fork testing position to only allow vertical position for testing.Only recording number of successful completions of objects within the 30 s trial.Scoring–sum score of successfully moved items across all six tasks.Fundamentally the GRT THA remains very similar to the original GRT designed by Woulle et al. . The chaThe changes to the testing procedures reduce time and effort for administering the test in a clinical environment. Due to the variability of grasps created by upper limb reconstructive surgeries, definitions of accepted grasp types and adaptations for the GRT THA were established. The original GRT specified three objects to be acquired using lateral grasp  and three using palmar grasp . The GRT THA allows object acquisition with any surgically provided grasp pattern, within specific documented instructions. Changes to grasp patterns include participants allowed to pick up the peg, videotape/book and paperweight with the thumb and another finger (as opposed to a key pinch between the thumb and index finger as required in the GRT). For the block, accepted grasp patterns include both a gross grasp of the block between all fingers and the palm of the hand (as in a tenodesis action) or between thumb and index finger. For the can, the grasp pattern must use at least three fingers and the cylinder must be grasped by the sides with the top exposed (mimicking a grasp required for drinking).https://neuraloutcomes.com/product/grasp-and-release-test/) once finalised. It is not expected that there would be a need for training for clinicians using the GRT THA as comprehensive instructions are provided in the instruction manual. The GRT THA testing kit can be purchased from this website and has a current cost of US$2500.The original GRT pre-test was considered important to allow for adjustment of neuroprosthesis parameters and practice in its use , therefoWithin the recommended battery of tests following upper limb reconstruction in people with tetraplegia, the GRT is currently the only standardised physical performance activity test with all others being patient-reported outcomes . The GRTThe commercial availability of the GRT and the revised GRT THA testing procedure provides opportunity for all centres currently performing upper limb reconstructive surgery procedures to be able to quantify changes in hand function. Increased uptake of such outcome measure use facilitates the ability to combine and compare results from all centres and provide meaningful information to health professionals, people with tetraplegia, and funders regarding the effectiveness of such procedures. The psychometric properties of the GRT THA are currently being investigated.


Topical estrogen is effective for treating postmenopausal vaginal atrophy. However, there is a potential risk of estrogen-related adverse effects. There is a need for finding effective non-hormonal treatment for vaginal atrophy. The topical application of moisturising agents, such as hyaluronic acid (HA), represents a promising non-hormonal treatment for the relief of vaginal atrophy. This study aimed to summarize the evidence regarding the efficacy of topical HA compared to topical estrogen in postmenopausal women with vaginal atrophy. The literature search covered English-published studies from database inception till February 2023. The search included the electronic databases of MEDLINE/PubMed, Cochrane Library, Web of Science, ProQuest, and Scopus, using the terms "Hyaluronic Acid" AND "Postmenopause" AND "Vagina” AND "Atrophy". Due to the diversity in reporting outcomes, meta-analysis was not feasible. A narrative synthesis with a systematic approach was conducted by vote counting of studies that included a direct comparison between topical HA and topical estrogen. Six studies were included. Intra-group comparisons showed that both interventions were significantly effective in alleviating the symptoms of vaginal atrophy and dyspareunia as well as improving vaginal pH and cell maturation index. However, inter-group comparisons in most studies showed that estrogen was superior to HA in relieving vaginal symptoms and improving vaginal pH, dyspareunia, and the cell maturation index. There is no evidence to show the superiority of HA to estrogen in the treatment of postmenopausal vaginal atrophy. However, the therapeutic efficacy of HA seems to be comparable to estrogen and considering its safety, HA can be used as an alternative to estrogen in patients who do not want to use estrogen. The available studies have several limitations, and the reporting of outcomes was considerably heterogeneous. Menopause is defined as the permanent cessation of menses following amenorrhea that lasts 12 consecutive months without the use of hormonal contraception [Decreased estrogen level after menopause leads to loss of cell proliferation in the vaginal epithelium, causing connective tissue damage with subsequent infiltration of leukocytes and macrophages . The infVulvovaginal atrophy constitutes an integral part of the genitourinary syndrome of menopause ,7. Most The North American Menopause Society stated that the treatment of vulvovaginal atrophy aims primarily to relieve subjective symptoms. First-line agents include non-hormonal, long-acting vaginal moisturizers . In womeAlthough the topical application of estrogen to the vagina proved its efficacy in reducing the atrophic vaginal changes and alleviating the symptoms , there iThere is a plethora of non-hormonal vaginal products that can improve the moisturization of the vagina and alleviate the vulvovaginal symptoms . Some vaThe present systematic review was conducted to summarize the evidence regarding the efficacy of topical HA compared to topical estrogen in postmenopausal women with vaginal atrophy.Materials and methodsMethodologyThis systematic review was conducted and reported according to the principles of the Cochrane Handbook for Systematic Reviews of Interventions, version 6 and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline .Research QuestionIs topical HA as effective as topical estrogen preparations for the treatment of vaginal atrophy in postmenopausal women?Research Aim and ObjectivesThis systematic review aimed to compare the efficacy of topical HA and topical estrogen in postmenopausal women with vaginal atrophy. The studied objectives we to compare the improvement in the symptoms of vaginal dryness between HA and topical estrogen and to compare the improvement in vaginal pH and maturation index of vaginal cells.Eligibility Criteria for the StudiesThis systematic review included comparative observational (cohort or case-control) studies and clinical trials. The literature search was limited to studies published in English from the database inception to February 2023. Studies were included if the studied subjects were postmenopausal women diagnosed with vaginal atrophy. Studies were eligible if they included a direct comparison between topical HA and topical estrogen regarding the alleviation of the symptoms of vaginal atrophy and dyspareunia as well as the changes in vaginal pH and vaginal cell maturation. Animal studies and studies that did not include a direct comparison between topical HA and topical estrogens were excluded. We also excluded conference abstracts, duplicate records, case reports, reviews, commentaries, editorials, and clinical guidelines.Search StrategyThe search included the electronic databases of MEDLINE/PubMed, Cochrane Library, Web of Science, ProQuest, and Scopus. The search covered all publications from database inception till February 2023. The search was conducted in February 2023. The used search terms included "Hyaluronic Acid" AND "Postmenopause" AND "Vagina” AND "Atrophy" and no filters were used. The first author screened the reference lists of retrieved articles by electronic search in order to find other potentially relevant studies.Selection of StudiesLiterature search and screening of the titles and abstracts were conducted by the first author. The first author retrieved the full text of potentially relevant articles and assessed the studies’ eligibility for inclusion in this systematic review. The second author checked the search process, the screening of the records, and the selection of the studies. Any disagreements were settled by consulting the third author.Data ExtractionThe first author extracted data from the eligible studies using a standardized data sheet. The extracted data included (a) the characteristics of the study ; (b) patients’ characteristics (age at the time of study as well as the age at menopause or the duration of amenorrhea); (c) the intervention and control treatments: form, concentration, and regimen; and (d) the outcomes: the symptoms of vaginal dryness , vaginal pH, and maturation index of the vaginal cells after treatment. The second author revised the extracted data to ensure consistency and clarity. Any disagreements between the first and second authors were settled by consulting the third author. The third author revised the extracted data and checked the methods used for data synthesis.Measured OutcomesThe primary outcome was an improvement in the symptoms of vaginal atrophy . The secondary outcomes were the change in vaginal pH and the maturation index of vaginal epithelial cells.Assessment of the Risk of Bias in the Included StudiesWe used the National Institute for Health and Care Excellence (NICE) checklists for randomized controlled clinical trials , cohort Data SynthesisThere were wide variations among the included studies in reporting the studied outcomes, with some studies reporting vaginal symptoms as a composite score while other studies reported each symptom separately. Also, vaginal pH and the maturation index were sometimes reported as numerical variables and at other times as categorical variables. Consequently, pooling the data through the meta-analysis methods was not feasible. We performed a narrative synthesis with a systematic approach for the studied outcomes. A narrative synthesis table was created to report - for each outcome - the number of studies showing statistically significant effects and the direction of effect. The data were combined using the narrative synthesis methods by vote counting the direction of effect .ResultsResults of Literature Search and Study SelectionThe conduction of the literature search yielded 160 records. Eighty-two records were duplicates and removed. Four records were published in languages other than English and were excluded. Then, we screened the titles and abstracts of the remaining 74 records, with the exclusion of 52 records due to the publication type (n = 32), non-relevance (n = 16), conduction on animals (n = 2) or in vitro (n = 1), and oral administration of HA (n = 1). The full texts of the remaining 22 records were sought, with the successful retrieval of 19 records while the full text of three records could not be obtained. The retrieved 19 records were assessed for eligibility to be included in this systematic review. Seventeen records were not eligible; 11 studies lacked a comparison group, or the comparator did not contain estradiol, four studies were conducted on premenopausal women, and two studies included patients with a history of cancer. Searching the reference lists of retrieved full texts yielded six potentially relevant records, out of which two were excluded (one was a duplicate and the other lacked an estradiol comparator). Finally, six studies were included in this systematic review , except one study , which wEvidence Synthesis of the Included StudiesEkin et al.  carried Le Donne et al.  carried Chen and co-workers  carried Jokar et al.  conducteDuque-Estrada et al.  carried Alvisi et al.  conducteAssessment of the Risk of Bias in the Included StudiesAs regards the selection bias, the ROB was uncertain in three studies -31 due tVaginal Atrophy Symptoms and Vaginal pHThe six studies reported a change in the symptoms of vaginal atrophy after receiving treatment. Different methods were used to describe vaginal symptoms in the studies, as most studies used a composite score ,29-31, wDyspareunia and Vaginal Cell MaturationThree studies reported a change in vaginal pH after receiving treatment ,28,30. DDiscussionSummary of the Main FindingsThe present systematic review was conducted to summarize the evidence regarding the efficacy of topical HA compared to topical estrogen in postmenopausal women with vaginal atrophy. The search of the electronic databases and reference lists resulted in the inclusion of six eligible studies in this systematic review ,27-31.Several studies established the efficacy of topical estrogens in alleviating the symptoms and cellular changes of vaginal atrophy . HoweverIn a normal vagina, glycogen breakdown produces glucose, which is converted into lactic acid, resulting in a vaginal pH ranging between 3.5 and 4.5. In postmenopausal women who do not receive hormonal replacement therapy, glycogen content gradually decreases. Moreover, there is reduced exfoliation of the vaginal epithelium. These factors will result in increased vaginal pH and a decrease in the normal lactobacilli flora . TherefoThe synthesis of this review indicated that both HA and estrogen were effective in relieving the symptoms of vaginal atrophy and dyspareunia as well as improving the vaginal pH and cell maturation index. However, estrogen was superior to HA in most studies. One study only reported that HA achieved significantly better outcomes than estrogen , while aOverall Completeness, Applicability, and Quality of the EvidenceThis systematic review summarized the current evidence on the efficacy of topical HA compared to topical estrogen as a treatment for postmenopausal vaginal atrophy. The results show that HA is effective in alleviating the symptoms and improving the vaginal pH and maturation index to reach nearly pre-menopausal levels. However, the results suggest that the efficacy of HA is inferior to estrogen. Meanwhile, other factors - besides the degree of efficacy - should be considered when recommending treatment for postmenopausal vaginal atrophy. As HA combines satisfactory efficacy with safety, it can be prescribed as a first-line treatment, particularly in women with mild symptoms. The use of estrogens can be kept for patients with moderate to severe symptoms or for those who do not improve on non-hormonal moisturizing preparations. This inference supports the recommendations of the position statement of the North American Menopause Society .However, the results of the present systematic review are limited by the observed limitations of the included studies. There are concerns regarding the selection and performance of ROB. Although the studies mentioned that randomization was performed, no details were reported to support this statement except in two studies ,28. The Furthermore, there was underreporting of the important outcomes of changes in vaginal pH ,29,31 anIn addition, we were unable to conduct a meta-analysis as the reporting of outcomes was heterogeneous across the studies, which is a common problem in studies investigating genitourinary symptoms . We perfA previous systematic review  addresseThe topical application of HA was both effective and safe. Our results support the recommendations of the position statement of the North American Menopause Society that HA can be used as a first-line treatment, particularly in mild vaginal atrophy. Estrogens can be used with moderate to severe symptoms or in non-responders as estrogen is expected to be more effective than HA in those patients. The restricted use of estrogens is due to the potential risk of estrogen-dependent cancers, heart disease, and stroke. Also, the use of topical estrogen in the case of women who experienced estrogen-dependent cancer may not be advisable.The limitations of the available studies warrant the conduction of future RCTs with adequate sample size, ample duration of follow-up and adherence to the criteria of high-quality RCTs, including proper conduction and reporting of randomization, allocation concealment, double-blinding, and complete reporting of the outcomes. The studies should endeavour to assess the FDA-recommended outcomes. In addition, future studies should explore whether certain patient-related factors  can impact the outcomes and perform subgroup analysis if such factors were identified.


Inflammations of the paranasal sinuses represent a common clinical picture. The annual prevalence of chronic sinusitis in Europe is up to 10% . In addiThe symptoms of sinusitis are varied  especially in the context of chronic sinusitis. While the diagnosis of acute sinusitis is made clinically, the clarification of chronic sinusitis requires extended imaging  and nasal endoscopy. Alternatively, an MRI examination and/or cone beam scan (DVT) examination of the affected region can also be carried out. If the findings are unclear, an odontogenic sinusitis needs to be discussed in the interface area of the clinical subjects of ear-nose-throat department (ENT) and the department of maxillofacial surgery.In addition to conservative treatment options for chronic sinusitis , surgical procedures  can also be considered. However, chronic sinusitis tends towards a high rate of recurrences. Therefore, in many cases only symptom control is achieved . In partFungal infections of the paranasal sinuses are rare cases. In particular, systemic diseases relevant to the immune system such as diabetes mellitus predispose to infections with atypical pathogens. Infections with Aspergillus in the area of the paranasal sinuses often only occur in a single paranasal sinus. Aspergillomas in the maxillary sinus are frequently associated with root canal treatment in the area of the upper jaw teeth due to overpressed root filling material into the maxillary sinus.With regard to the medical history/previous illnesses and symptoms of the patient, an atypical chronic sinusitis should be considered with these indications. Imaging procedures such as computed tomography often show a typical ring-shaped uptake of contrast medium with accompanying polypoid swelling of the sinus´ mucosa in the respective paranasal sinus  9]. Fur. Fur9]. The decisive therapy pillars for sinusitis associated with aspergillosis consist of anti-infective therapy , surgical removal of the aspergilloma and inflamed mucosa (osteoplastic maxillary sinus surgery), and treatment of the concomitant disease  . In the In addition, it is particularly important to rule out invasive forms of aspergillosis. The therapy of immune-relevant comorbidities requires interdisciplinary treatment. Up to now, there is little data on the long-term results of aspergilloma-associated sinusitis. The follow-up consists of regular clinical examinations as well as additional imaging procedures , especially in the case of odontogenically associated aspergilloma infections of the paranasal sinuses.Fungal infections are a rare cause of sinusitis. A detailed anamnesis and clinical examination of the patient should be carried out, particularly in the case of therapy-refractory forms of chronic sinusitis. It is also important to consider atypical causes and disease connections  when dealing with chronic sinusitis. Interdisciplinary diagnostics and therapy are crucial for the successful treatment of this rare entity.


Proteases, including serine proteases, are involved in the entire life cycle of plants. Proteases are controlled by protease inhibitors (PI) to limit any uncontrolled or harmful protease activity. The role of PIs in biotic and abiotic stress tolerance is well documented, however their role in various other plant processes has not been fully elucidated. Seed development is one such area that lack detailed work on the function of PIs despite the fact that this is a key process in the life cycle of the plant. Serine protease inhibitors (SPI) such as the Bowman-Birk inhibitors and Kunitz-type inhibitors, are abundant in legume seeds and act as antinutrients in humans and animals. Their role in seed development is not fully understood and present an interesting research target. Whether lowering the levels and activity of PIs, in order to lower the anti-nutrient levels in seed will affect the development of viable seed, remains an important question. Studies on the function of SPI in seed development are therefore required. In this Perspective paper, we provide an overview on the current knowledge of seed storage proteins, their degradation as well as on the serine protease-SPI system in seeds and what is known about the consequences when this system is modified. We discuss areas that require investigation. This includes the identification of seed specific SPIs; screening of germplasms, to identify plants with low seed inhibitor content, establishing serine protease-SPI ratios and lastly a focus on molecular techniques that can be used to modify seed SPI activity. Wheat seeds mainly consist of the embryo and the endosperm. Both facilitate seed germination as well as subsequent plant growth and development. The wheat embryo develops from the oosperm and holds a large amount of sugar, fats and proteins that represents 2.8 – 3.5% of the total seed weight  and the legumain family (C13), all stages of the plant life cycle . The memSerine PIs that control serine protease activity are ubiquitously present in many plant species. They have also diverse biological functions and can play dual roles with their physiological functions conserved and their functions diversified by a positive selection pressure . Little The two major groups of SPI in legume seeds are the Kunitz-type inhibitors (KTIs) and Bowman-Birk inhibitors (BBIs)  trypsin inhibitor activity  to produce inhibitor mutants would be a possible future strategy. Silencing such individual seed SPIs would allow to unravel specific and unique functions in the development of viable seeds. Application of GE, such CRISPR/Cas9 and TALEN , has resThe original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.JV and KK are the main author of the perspective article completing the writing of the first draft of relevant literature. All authors contributed to the article and approved the submitted version.


IntroductionEmergency medicine (EM) postgraduate medical education in Canada has transitioned from traditional time-based training to competency-based medical education (CBME). In order to promote residents through stages of training, simulated assessments are needed to evaluate residents in high-stakes but low-frequency medical emergencies. There remains a gap in the literature pertaining to the use of evaluative tools in simulation, such as the Resuscitation Assessment Tool (RAT) in the new CBME curriculum design.MethodsWe completed a pilot study of resident physicians in one Canadian EM training program to evaluate the effectiveness and reliability of a simulation-based RAT for pediatric resuscitation. We recorded 10 EM trainees completing simulated scenarios and had nine EM physicians use the RAT tool to evaluate their performances. Generalizability theory was used to evaluate the reliability of the RAT tool.ResultsThe mean RAT score for the management of pediatric myocarditis, cardiac arrest, and septic shock (appendicitis) across raters was 3.70, 3.73, and 4.50, respectively. The overall generalizability coefficient for testing simulated pediatric performance competency was 0.77 for internal consistency and 0.75 for absolute agreement. The performance of senior participants was superior to that of junior participants in the management of pediatric myocarditis (p = 0.01) but not statistically significant in the management of pediatric septic shock (p=0.77) or cardiac arrest (p =0.61).ConclusionOverall, our findings suggest that with an appropriately chosen simulated scenario, the RAT tool can be used effectively for the simulation of high-stakes and low-frequency scenarios for practice to enhance the new CBME curriculum in emergency medicine training programs. Pediatric resuscitations are considered low-frequency, high-stakes events in emergency departments in North America ,2. One cPost-graduate medical education in Canada is in a state of transition from traditional time-based training to competency-based medical education (CBME). As opposed to determining competency based on the number of years of training, CBME aims to do so by having residents prove proficiency in a set number of clinical skills or tasks. The Royal College of Physicians and Surgeons of Canada has implemented Competence by Design (CBD), its own unique model of CBME . The fouThe transition to CBME in emergency medicine in Canada was in July 2018 [While many assessment tools for EM simulation scenarios have been created and arguments for their validity presented, a limited number have been integrated into the EM residency curriculum as a form of assessment of competence . With thQueens University  created a resuscitation assessment tool (RAT) with the goal of utilizing it within the new CBD curriculum. The RAT generates entrustment scores through an anchored global assessment scale. Recently, the research team from Queens University that created the RAT used it to compare resident performance in the clinical environment relative to the simulated (SIM) environment . Using tThere remains a gap in the literature on the use of tools such as the RAT in the new CBME curriculum design, specifically pertaining to the assessment of competence in pediatric resuscitation and pediatric EPAs. There are specified performance expectations for a required number of exposures to pediatric acute care cases, with accompanying assessments of competency in these settings. Additionally, while there is a clearly established transferability from simulated practice to clinical competence for procedural skills , that saOur study aims to evaluate the reliability of the RAT as a tool for assessing emergency medicine trainee competence, specifically in pediatric resuscitation scenarios. We aim to achieve this by determining whether the RAT can communicate consistent results independent of the assessor (rater) and if it can correctly identify residents who may need more support in a specific area of competence. The overarching goal of this study is to understand how to strengthen pediatric simulated curricula for EM residents participating in the CBME framework.A prospective observational cohort study of resident physicians in one Canadian EM training program was used to evaluate the effectiveness and reliability of a simulation-based RAT for pediatric resuscitation. The study took place between January 2019 and July 2021 and was carried out in the KidSIM Lab at the Alberta Children’s Hospital in Calgary, Alberta, Canada. The study was approved by the Conjoint Health Research Ethics Board at the University of Calgary.Study settingThe study took place at the University of Calgary’s Cumming School of Medicine Department of Emergency Medicine over an 18-month period of time. High-fidelity and age-appropriate mannequins were utilized in the KidSIM Center at the Alberta Children’s Hospital. Performance was video recorded from three fixed camera angles to allow adequate views of the trainee, the mannequin, and the monitors.Study participantsEmergency medicine residents (FRCPC-EM), pediatric emergency medicine fellows, and family medicine residents completing a special competence year in emergency medicine (CCFP-EM) were eligible to participate. We recruited 10 residents, as determined by local resident volume and availability. Participation was voluntary, and residents were assured that their performance would not be shared with anyone outside of the study (program directors or otherwise). They were informed, prior to consenting to participate, that there would be raters from within Calgary as well as across the country. Written consent was obtained from all participants, including video recordings of their performances in the simulation lab.Assessor trainingA purposeful sample of practicing EM physicians involved in CBME simulation training for residents was chosen as raters. The authors utilized frame-of-reference training to prepare raters and provided an orientation to the RAT tool prior to reviewing each resident’s performance. Each rater received a practice video of a resident physician not participating in the study completing a simulated scenario. The rater was required to watch the video and use the RAT tool to evaluate the performance. After the practice video, a member of the research team (MM) met with each participant over a 30-minute period to go over their evaluation, compare RAT evaluations, and discuss any questions that came up about the tool. Raters were then asked to rate the performance of the study participants in all three scenarios, as detailed below.A total of nine EM physicians were trained as assessors: three of those physicians were local and unblinded, and six were external EM physicians from across Canada who were blinded to each resident’s level of training. Apart from EM training, all raters had specific interests and training in simulated practice, curriculum design, and residency education.Each EM physician rated four residents for a total of twelve total evaluations. Each resident was reviewed by one unblinded rater and two blinded raters. Raters were blinded to each resident's level of training. Blinded as well as unblinded raters were recruited to ensure that scores were not biased by the rater's awareness of the resident’s year of training. To further assess any inconsistencies in rating, all nine EM assessors rated one of the residents.Measures (RAT)The RAT was derived from a prior assessment tool, the Queen’s simulation assessment tool (QSAT). The QSAT was recently modified in the context of the implementation of CBME to create the resuscitation assessment tool (RAT), with the goal of utilizing it within the new CBD curriculum. The RAT generates entrustment scores through an anchored global assessment scale. The scoring system was derived from the QSAT by developing generic behavioral anchors for resuscitation performance using a modified Delphi process for each domain and replacing the global assessment scale with an entrustment scale. A score of one on the scale translates to "resident only observed the skill," whereas a score of five communicates that the resident has mastered the skill and can supervise trainees Figure .Simulated scenario administration and evaluationEach resident completed three standardized simulated cases in the simulation labs. They were each assigned the role of team leader. As described on the Royal College website, the goal of this EPA is to lead a team of healthcare professionals in the emergency department to care for a patient with a medical or surgical life-threatening condition. Their performances were video recorded for later review. KidSIM nurses supported and facilitated the scenarios, keeping each scenario consistent for each resident. Though all the staff was experienced with the mannequins and the scenarios, we reviewed each scenario 30 minutes prior to each simulation session. There were two simulation days, and each day the same KidSIM staff served as facilitators. The scenarios were based on EPA 3.1: resuscitating and coordinating care for critically ill patients . Our cases included pediatric myocarditis, septic shock (appendicitis), and cardiac arrest. Details on these case scenarios can be found in the appendices.Statistical analysisDemographic characteristics of the participants, such as gender and level of training, were summarized with descriptive statistics (count and percentage). The RAT scores of the three scenarios were summarized with a mean and standard deviation.project.org) and "gtheory" packages to estimate the variance components of participants, scenarios , and raters. The three two-way interactions between all three of these variables  and the three-way interaction effects (raters x participants x scenarios) were confounded with random error as a function of the fully crossed design. The generalizability coefficients for internal consistency and absolute agreement of the following two analyses were calculated manually:Generalizability theory was used to evaluate the reliability of the RAT tool. We used R statistical software (www.r-(1) A two-random-facet design where both the effects of the rater and scenario are considered random Figure .(2) A two-facet design with one facet fixed. The facet of the rater was considered random, and the facet of the scenario was considered fixed since the same scenario could be used to evaluate the resident’s performance Figure .The variance coefficients were then used to inform a decision study (D-study) to determine the optimal combination of raters and scenarios to maximize the reliability of the assessments.Due to the small sample size and skewed distribution of the data, non-parametric tests were used for validity tests. The Wilcoxon rank sum test was used to compare the performance of junior (post-graduate years one and two) and senior participants  in the three scenarios. The Wilcoxon signed-rank tests were used to compare the performances within three scenarios. The RAT score was the only primary outcome we examined. The structure of analysis plan was organized as (1) demographic information, (2) generalizability theory (reliability), and (3) validity.Participant demographicsA total of 10 emergency medicine residents participated in the study, with four women  and six men . Eight participants were emergency medicine residents (FRCPC-EM) from post-graduate year one to five , one was a pediatric emergency medicine fellow (PGY-4), and one was a former family medicine resident completing a year of emergency medicine training (CCFP-EM) (PGY-3).Data summaryThe mean RAT score for the three pediatric simulated resuscitation performances across participants and raters was 3.97. The mean score for the management of pediatric myocarditis, cardiac arrest, and septic shock (appendicitis) across raters was 3.70, 3.73, and 4.50, respectively. Table Generalizability studyThe variance components for testing the participants across three pediatric resuscitation scenarios and 10 raters are presented in Table Decision studyA decision study (D-study) was conducted as a hypothetical calculation whereby the number of raters and scenarios were manipulated to achieve a reliability coefficient of 0.70. We found that increasing the number of scenarios did not seem to improve the reliability coefficient. Based on the hypothetical projection of the D-study, two scenarios and six raters would be sufficient to achieve a reliability coefficient of 0.70 Table .There was an agreement between blinded and unblinded evaluators throughout each scenario.Validity evidenceThe performance of senior participants was superior to that of junior participants in the management of pediatric myocarditis . The performance difference in the management of cardiac arrest and septic shock (appendicitis) didn’t yield statistical significance . We found that across all levels of training, residents performed better on the septic shock (appendicitis) case and consistently scored lower on the myocarditis and cardiac arrest cases   case and lower on the myocarditis and cardiac arrest cases Figure . This waLimitationsDespite providing support for the use of the RAT tool in the emergency medicine CBD curriculum, there are a few noteworthy limitations that deserve mention in our study. Given the small sample size, the variability in resident scores may be overstated, and the generalizability of our results should be taken in context. While the low number of participants is a limitation, the lack of variance among our residents and raters gives important information on the structure of simulated scenarios moving forward. Future work with a variety of challenging cases would be important to assess the variance between learners based on experience and skill level.The authors were initially concerned that the data collection could also carry inherent bias. We recruited three local raters, all of whom knew the residents they were rating. This could have created a bias in the scores given. In contrast, blinded external raters were also used, and they were found to have an agreement with the local raters Table . UnfortuThe RAT was found to be reliable when raters are appropriately trained and there is good agreement with zero variance between multiple raters. Therefore, the RAT can be trusted to give residents consistent evaluations. Additionally, the tool was able to reliably identify resuscitation topics that residents struggled with, which will help educators choose content for future simulated scenarios.Finally, we also found that the resident level of training and rater blinding did not impact the reliability of the tool. Overall, this study demonstrates that the RAT is a reliable tool to implement in the evaluation of emergency medicine residents for pediatric resuscitation scenarios in a simulation curriculum within CBD training.


Bangladesh has made substantial progress in maternal health. However, persistent inequities in service use undermine the achievements at the national level. In 2007, the government introduced a Maternal Health Voucher Scheme (MHVS) to reduce barriers to service utilization. The current study explores the impact of MHVS on reducing distance inequality in utilization across the maternal and newborn continuum of care (MNCoC).A cross-sectional survey was conducted from October’2017 to April’2018 in four selected MHVS sub-districts of Chattogram and Sylhet Divisions of Bangladesh. 2,400 women with at-least one child aged below two years were randomly selected. Both bivariate and multivariate analyses were carried out to explore the absolute and relative influence of the voucher scheme and chi-square test was used for hypothesis testing.Nineteen percent of the women were MHVS beneficiaries and 23% of them lived within 5 km of the health facility. Among the beneficiaries no significant differences were observed in the utilization of at-least 4 antenatal visits, skilled-assistance at delivery, postnatal care, and MNCoC between those living closer to the health facility and those living far away. However, a higher facility delivery rate was observed among beneficiary women living closer. By contrast, for non-beneficiaries, a significant difference was found in service use between women living closer to health facilities compared to those living further away.The study found the use of MNCoC to be similar for all MHVS beneficiaries irrespective of their distance to health facilities whereas non-beneficiary women living further away had lower utilization rates. MHVS could have potentially reduced distance-related inequality for its beneficiaries. However, despite the provision of transport incentives under MHVS the reduction in inequality in facility delivery was limited. We propose a revision of the transportation incentive adjusting for distance, geographical remoteness, road condition, and transport cost to enhance the impact of MHVS. Over the past decade, Bangladesh has made substantial improvements in maternal and child health. The maternal mortality ratio in the country has declined from 574 in 1990 . The neoEvidence from low and middle-income countries shows that although many women visit health facilities during pregnancy for screening of risk factors, pre-existing medical conditions, and current health status, very few do this, at the intervals recommended by the World Health Organization (WHO) . In BangIn many developing countries programmatic interventions like voucher schemes are being tested to boost service utilization across the whole continuum of maternal and newborn care by providing cash or in-kind incentives to users as well as to providers. The schemes aim to increase service access as well as demand for services among targeted groups and are used to reduce out-of-pocket expenditure for health care for households at risk of not seeking care in the absence of the subsidy . StudiesThe government of Bangladesh introduced the Maternal Health Voucher Scheme (MHVS) in 2007 with the aim of improving maternal and child health outcomes in rural areas. Operating in 53 out of the 556 sub-districts of the country in 2018), the voucher scheme is targeted to poor pregnant women for their first two children. To be eligible for the voucher, pregnant women need to be permanent residents of the area of intervention, landless (i.e. owning less than 6534 square feet of land), have a monthly average income of household less than 1.25 U.S. Dollars per day . The benefits of MHVS cover three antenatal care visits, delivery at a health facility or at home with a qualified provider, one postnatal check, management of maternal complications including cesarean delivery where required, free medicines, cash allowances for transportation  and cash incentive to deliver at a health facility or at home with a qualified provider. The voucher can be used in both public hospitals , the major public health facility at the sub-district level) and designated private and non-government facilities. Provider facilities and individual staff also receive payments for each service provided to the scheme members , the vou. There iResearch and Ethical approval was taken from the Research Review Committee (RRC) and the Ethical Review Committee (ERC) of the International Centre for Diarrhoeal Disease Research, Bangladesh  before initiating the research study. Written informed consent was taken from all study participants before conducting the interviews. The consent process involved informing study participants about the study, their involvement as respondents, their right to withdraw or not to answer any of the questions, and also any risk or benefit that the study may entail.Before conducting interviews with randomly selected women written informed consent was taken after she was informed about the study objectives and her involvement in the study.Following a cross-sectional study design, a household-based survey was conducted from October 2017 to April 2018. A pre-tested questionnaire was used to collect the required data. The questionnaire was pretested among some MHVS and non-MHVS women in one of the study sites. Based on learning from pretesting the questionnaire wording of some of the questions was made easier to understand for the target group people. Interviewers were trained to make the question understandable to respondents in the local language. The household survey collected information on the socio-demographic and economic characteristics of study respondents, health-seeking behavior around maternal and newborn care, access and use of maternal health voucher scheme, geographic location of households and respective health facilities, etc.Four sub-districts where the MHVS is being implemented were chosen as study sites from two divisions of the country, which are low-performing in terms of some MNCH indicators when compared to national rates . The perRamu and Teknaf sub-districts were selected from the Chattogram division which is situated in the south-east region of the country and Sreemangal and Sulla sub-districts from the Sylhet division situated in the north-east region of the country see . Each ofConsidering 31% as the facility delivery rate in MHVS areas , to deteThe data collection team consisted of one male and one female Field supervisor and twenty interviewers (Research Assistants). Field Supervisors were recruited from the head office and interviewers were recruited locally based on their previous interview conduction and supervisory experience considering their capacity to understand the local language quickly. Interactive training sessions were organized to discuss study objectives, the questionnaire, sampling data collection, and management techniques. After the training, field testing of the questionnaire along with pilot interviews were carried out. Interactive discussions were then held to discuss lessons learned, challenges faced from the pilot interview, and how to overcome them.Household listing was carried out in villages selected from four study sub-districts using the Probability Proportional to Size (PPS) method . A totalWomen who had at least one live birth within the past 24 months were considered eligible to become respondents for the study. From the household listing, 2948 eligible women were identified. For conducting face-to-face interviews, 2630 (out of 2948) randomly selected women were attempted. Finally, 2400 women (91% response rate (2400/2630)) were successfully interviewed see . ReasonsThe potential accessibility variable for coverage of maternal and newborn continuum of care in the study was taken as the distance from the mother’s residence to her local Upazila Health Complex.Women who were members of the MHVS were termed ‘MHVS’ while those who were not members of the voucher scheme were termed ‘Non-MHVS’. For analytical purposes, the variable regarding distance to UHC from villages where women reside was recoded into two categories, within or further than 5 km from the UHC. Households from where women were chosen for interview were all GIS mapped. We also recorded the GIS code of all upazila health complexes from the study areas which allowed us to estimate the exact distance of women’s residences from the health facilities in kilometers. Categorization of the variables ‘birth order’ and ‘mother’s age at birth’ were done based on the median scores. Using data for asset with substantial frequency such as–ownership of household assets, source of drinking water, types and sharing of toilet facility, ownership of livestock, ownership of homestead and land, source of cooking fuel, the main material of floor, roof, and wall, the average number of people sleeping in one room, a wealth index as a proxy measure of economic status was created in tertiles (i.e. distributing one-third respondent in each of three categories) applying principal component analysis , 29, 30.Dependent or outcome variables were categorized as binary variables for each stage of the maternal and newborn continuum of care (MNCoC). Utilization of antenatal services was categorized as those women who have received at least four versus fewer than four antenatal visits . FacilitVariables regarding postnatal care received from a qualified provider within 2 days of delivery were created by grouping those women who received postnatal services for themselves or their children within 2 days of delivery from any qualified providers /Sub-Assistant Community Medical Officer (SACMO)) versus those women who did not receive these services from any qualified provider .It was considered that a mother was a recipient of the continuum of maternal and newborn care if she received all of the following services ‐ at least 4 antenatal visits, facility delivery or skilled birth attendance, and postnatal care from trained providers within 2 days of delivery .Bivariate and multivariate analyses were carried out to the explore absolute and relative impact of independent variables on outcome variables.In Bivariate analysis, we examined associations or absolute impact of major independent variables i.e. voucher membership status and distance to facility or upazila health complex (UHC) with outcome variables i.e. utilization of individual stage and continuum of maternal and newborn care . As a measure of association, we used the Pearsons chi-square test statistic . CHISQ cFor multivariate analysis, to have a parsimonious model, service utilization is modeled using binary logistic regression following a stepwise method . SignifiThe Dependent or response variable was defined as binary contrasts, which take the value of 1 if a woman accessed the continuum of maternal and newborn care, and zero otherwise.i = Pr(yi = 1) in the form of the regression equationWe modeled the probability of utilizing continuum of maternal and newborn care which we defined as π1 and β2 represent the coefficient for the effect of voucher and effect of distance to UHC respectively on the probability of continuum of maternal and newborn care utilization, with the independent variables Voucheri and Distancei respectively being defined as 0/1 contrasts as to whether woman i received a voucher, and whether she lived within 5 kilometers of UHC. The effect of other characteristics  are captured in the vector of control variables zi.where βi *Distancei) was also considered to be included in the model to test whether the effect (coefficient β3) of the voucher membership on utilization of the continuum of maternal and newborn care varies between within 5 km and beyond 5 km of UHC compared to that of non-voucher mother. Other independent variables as control variables were included in two models  to ensure these effects are robust to women’s and children’s socioeconomic and other background characteristics. Predictor variables were included or excluded from the model step by step as per the criteria of the stepwise model selection procedure such as probability in (i.e. p<0.05) and probability out (i.e. p>0.10). Likelihood ratio tests (LRT) were used to understand the goodness-of-fit of the models as well as to understand the significance of the odds ratio associated with each category among the independent variables.The multivariate model is specified as the main and interaction effect model, which captures the effect of voucher receipt and distance to UHC or health facility along with other potential confounders on service utilization. An interaction between voucher membership status and distance to UHC or health facility  compared to female (48.1%). Birth order of the last live birth in the last two years was two or below in the case of 59.5% of women. 19% of the women were members of the maternal health voucher scheme in four intervention study sites. 23% and 77% of respondents were from villages within and beyond 5 km of UHC respectively.For bivariate analysis we followed a procedure reported . Based oWhile exploring distance to health facility-related inequality within the non-voucher mother group, significant (p<0.001) differences were observed in utilisation of 4 or more antenatal visits, facility delivery, skilled birth attendance, PNC from qualified providers within 2 days of delivery, continuum of maternal and newborn care between those who lived within 5 km of UHC and those residing beyond 5 km of UHC. Among non-voucher scheme women within to beyond ratio in utilization of maternal and newborn continuum of care was found comparatively higher (2.1) than that of other maternal and newborn care services.From the bivariate analysis results differences in utilization of maternal and newborn care between women residing within and beyond 5 k.m. of UHC were found higher  among non-voucher women than that of voucher women with some exceptions regarding utilisation of facility delivery . Hence, In The existence of a difference in access to the continuum of maternal and newborn care between women residing within and beyond 5 km of UHC was significantly 0.6 times less likely for voucher women than of non-voucher women. MHVS recipients and those residing within 5 km of their local UHC were respectively 3.2 and 1.7 times more likely to access the continuum than their counterparts. Women from low and middle wealth index categories had respectively 0.2 and 0.5 times lower odds of MNCoC utilization compared to women from higher wealth index categories. Likewise, women with no education and those with primary level education had 0.4 and 0.5 times lower odds respectively compared to those with secondary or higher levels of education. Further, the use of MNCoC was less likely among women with a girl child (AOD 0.8) and of birth order more than 2 (0.5) compared to their counterparts. Women with age at first birth being more than 25 had a 1.6 times higher odds of MNCoC utilization compared to their counterparts .From the model with potential confounders excluding socioeconomic status variable, it was revealed that the difference in utilization of continuum of maternal and newborn care between mothers of MHVS residing within and beyond 5 k.m. of UHC was found to be significantly 0.5 times less likely compared to the mothers not having MHVS membership. Likelihood ratio test (LRT) indicate inclusion of socioeconomic status variable influence the model significantly.The current study analyzed factors associated with the utilization of different components of maternal and neonatal care and more specifically with the Maternal and Neonatal Continuum of Care. The bivariate analysis showed that the use of maternal and neonatal care services and the MNCoC was similar for all voucher members irrespective of the distance between their residence and the health facilities except for facility delivery. On the other hand, for non-voucher members significant differences were observed for all components of maternal and neonatal care and the MNCoC between those living further away from health facilities and those living closer. The rates were much lower for those living further away indicating a significant distance-related inequality among non-voucher women.However, it should also be mentioned that despite the positive influence on the reduction of distance-related inequality, the rate of service use among voucher members was lower than optimal; MNCoC for voucher members reaching only 38% and individual components of maternal and neonatal care ranging between 45.6% to 63.8%. The reasons behind this low rate of service use, particularly for MNCoC, need to be further explored to ensure the benefits of the voucher scheme reach its target population and the goal of universal coverage of maternal and neonatal care is achieved.In the face of the current almost stagnant rate of maternal mortality in Bangladesh for the last two decades, MNCoC has been considered to be an important determinant of safe motherhood practices. Earlier studies have indicated that women using the complete CoC were more likely to experience positive maternal outcomes  .Given the importance of MNCoC, the current study explored the determining factors of MNCoC use among voucher and non-voucher women. The findings from the multivariate analysis suggest that along with voucher membership, distance to health facilities from villages, mothers’ socioeconomic status, education, age at first birth, sex of children, and birth order, all had significant associations with utilization of MNCoC. The analysis explored the association of interaction term between distance and membership of MHVS which turned out to be significant and negative. This may indicate a narrowed distance-related inequality in MNCoC use among voucher members.The positive relation of MHVS with reduced distance-related inequality regarding access to and utilization of a continuum of maternal and newborn care is notable: this association is more substantial than that on individual components of maternal and newborn care services. The influence is retained after controlling for other variables that are known to be determining factors of healthcare access such as educational attainment and socioeconomic status.Evidence from earlier studies indicates that distance to a health facility and transport availability and cost are significant barriers to access to facility-based care , 11, 35.The MHVS provides a flat payment of BDT 100 ($1.4) to cover the transportation cost for each visit with a ceiling of four visits. The present findings indicate that as a priority, the MHVS scheme administrators should revise the transport incentive to accommodate higher reimbursement for remote areas  in order to enhance the impact of MHVS on service use and attainment of the continuum of maternal and neonatal care. We recommend consideration of alternative mechanisms for reimbursement of transport fees to reduce the geographical access barrier such as reimbursement based on distance or community-based transport models with revolving funds to ensure that maximum returns are achieved from national investment in the voucher scheme.According to the Tanahashi framework five successive sequential stages of service coverage, namely availability, accessibility, acceptability, contact, and effectiveness, need to be equally addressed while designing any health interventions to improve access to healthcare . FollowiWhile exploring the socioeconomic characteristics of the MHVS members we noticed the presence of a significant number of beneficiaries from higher socioeconomic status whereas the MHVS was meant for the low-income population. This points to the challenge of mistargeting of the scheme which limits the effectiveness of the scheme in enhancing the use of maternal and neonatal care services among this particular group of population.In addition to the challenge of mistargeting, the current study also identifies gaps in maternal and neonatal healthcare service use which warrants further in-depth exploration to modify or redesign the current voucher scheme in order to maximize its reach and efficiency. In this relation, qualitative research could be designed to understand maternal and neonatal care-seeking behavior, particularly among low-income rural populations, the reasons for low utilization of maternal and neonatal care, and the experience of beneficiary and non-beneficiary women in accessing maternal and neonatal care which can eventually feed into modification or redesign of the current scheme.The findings from the current paper emphasize the potential positive influence of MHVS on maternal and neonatal care utilization. The current study findings support the scaling up of the scheme in the remaining sub-districts of Bangladesh to facilitate improved access to and utilization of maternal and newborn continuum of care. Demand-side financing mechanisms like the MHVS have the potential to support the achievement of universal coverage of maternal and newborn care across the continuum of care, particularly in regions where geographic or distance-related inequality is a major challenge.The strength of the study lies in its concentrated analysis of distance-related inequality in access to maternal and newborn care. Literature review indicates there are several articles regarding impact evaluation, and lessons learned from the voucher scheme but there is very little scientific evidence regarding the role of the voucher scheme in reducing distance inequality in maternal and newborn health service utilization. Another strength of the manuscript is that it provides very recent evidence on the role of voucher schemes in reducing distance inequality regarding the utilization of a continuum of maternal and newborn care. The limitation of the study lies in the fact that the data collection was carried out in the low-performing divisions of the country and hence the findings are more applicable to the settings where utilization of maternal and newborn care is comparatively lower. Having said that the significance of the findings is greater for this reason as the impact is expected to be greater for areas where the maternal and newborn health indicators are adverse. The study used the wealth index as a proxy measure of socioeconomic status created from the asset ownership data of respondents instead of income data as income data are not very reliable in settings such as this.One other limitation lies in the fact that the use of MNCoC and all individual component of maternal and neonatal care was high among MHVS members compared to non-MHVS members in all settings which could be a result of the influence of other incentives offered in the scheme . The higher socioeconomic status of a segment of the voucher recipients compared to the non-voucher women might have some influence also. However, due to the focus of the study towards distance-related inequality, these factors were not explored in detail. Lastly, the data was cross-sectional in nature which limits drawing specific causal relationships.S1 Table(DOC)Click here for additional data file.S1 File(DOCX)Click here for additional data file.


Editorial on the Research TopicHirschsprung disease: genetic susceptibility, disease mechanisms and innovative management in the multi-omics eraHirschsprung disease (HSCR) is a puzzling subject for researchers and the story of its etiology as well as non-surgical cures have been the subject of extensive ongoing research . HSCR isHSCR is a disease that significantly affects patients and families, and the current cure is exclusively surgical. The promise of the Omic-Era is encouraging because research is being undertaken to identify niches in which researchers and physicians can collaborate and improve the outcomes for patients affected by this terrible disease . The eraFan et al. report the unusual finding of an anorectal malformation (ARM) with HSCR . ARM and HSCR are rarely reported together. In this study, the authors report an overall incidence of 2.4%–3.4% of cases. The paper is exciting and very precise, with spectacular images. Everything is explained in detail, but importantly, in the case of anal atresia, the simultaneous occurrence of HSCR should be considered.Iskandar et al.). RET's somatic mosaicisms have been identified in HSCR but are poorly recognized. Many of the contributions to this special issue highlight the frequency of rs2435357somatic mutation of RET in HSCR patients. Iskandar et al. suggest that somatic mosaicism in HSCR patients is not uncommon, supporting the complexity of the pathogenesis of this gastrointestinal disorder . They confirm that the RET rs2435357 is a paramount genetic risk factor for HSCR patients. With the help of molecular genetics, it is even possible to detect specific changes in the patient's genetic information. The authors rightly speak of a mosaic status. In this context, RET rs2435357 is of particular importance in HSCR patients. It would be interesting to identify the burden of each mutation in causing HSCR in the future.The REarranged during Transfection (RET) is one of the most significant genes discovered by 24 genes associated with HSCR  statistical method. Robust regression uses an iterative approach to assign a weight to each data point. The RLM algorithm uses the least-squares approach to identify the curve that outbursts the data bulk. The final event is to minimize the effects of outliers. These authors used RLM for screening plasma human autoimmune antigen microarrays. They quantitatively assessed enzyme-linked immunosorbent assay (ELISA) values with single-stranded DNA (ssDNA) antibody levels. They found that ssDNA antibodies in HSCR plasma were considerably higher than those in healthy and disease controls. Furthermore, ssDNA antibodies differentiated HSCR from non-HSCR patients, accomplishing an area under the curve (AUC) of 0.917, harboring a sensitivity of 96.99% and a specificity of 74.63%. The considerations of this work are interesting, especially since they mean an extension of diagnostics. The occurrence of the ssDNA antibody could be promising, especially in premature babies.Ji et al. may help us understand one of the life-threatening conditions associated with HSCR. Neuroimmune instruction intercedes the incidence and progress of enteritis. Single-cell RNA sequencing has been critical in decrypting several intracellular processes and signaling mechanisms in the last few years. Both human and mouse gut nervous system (ENS) components demonstrate that healthy gut neuronal cells prompt mediators and cell surface molecules, which can interconnect with innate and adaptive immunologic pathways. The enhancement of the neuromodulatory effect may prevent this entity from occurring. Vasoactive intestinal peptide, substance P, and neuropeptide Y carry a cationic charge that can break the bacterial membranes and kill the microorganisms. The authors describe the characteristics of the interaction between intestinal nerve cells and immune cells. We do not understand in detail what influences the cells in the hypoganglionic section of the megacolon in promoting the inflammatory process, nor the impact of the ganglion cells of the euganglionic megacolon. Understanding the interaction between ganglion cells and immune cells in the case of postoperative enterocolitis seems even more difficult. Is this caused by a disturbance in the peristalsis behind it, even though the colon should be functioning after the intervention? Does residual stenosis play a role? Is sphincter achalasia a possible cause? Based on these questions, this topic warrants further exploration.We are still searching for the etiology of HSCR, and the findings of A few centuries after the initial discovery of congenital megacolon in 1691 by Frederick Ruysch, a Dutch Anatomist, and its detailed description in 1886 by Harald Hirschsprung, a Danish pediatrician, HSCR is still very challenging. It will need a comprehensive platform of tools and minds to understand in detail the etiopathogenesis, broaden diagnostic tools, and set up a non-surgical treatment. Scientists and physicians need to apply future research efforts to tackle this Sisyphean task.