S and M were implanted in 95 (46.6%) and in 76 (37.3%) of patients, respectively. The 30-day and late mortality rate were 0.5% and 4.4%, while the new permanent pacemaker implantation rate was 4.4%. Mean pressure gradient was 13.0 mmHg at discharge, reaching 11.0 mmHg at 1 year; while the mean EOA was 1.5 cm2 at discharge remaining stable up to 1 year. No moderate or severe leakages were present at discharge or at 1 year. NYHA class improved by ≥ 1 level in 55.1% of the patients at discharge and in 69.4% of the patients at 1 year. 1-year outcomes of SAVR with the Perceval sutureless valve in Japanese patients were favorable. This valve offers a promising alternative to conventional biological AVR in this Japanese population.Sutureless offers an alternative to standard valves in surgical aortic valve replacement (SAVR). We sought to confirm the efficacy and safety of the Perceval sutureless valve in Japanese patients. Prospective observational study of 204 patients who underwent SAVR with Perceval at 19 sites in Japan between March and December 2019. The primary outcomes were 30-day mortality and postoperative complications; the secondary outcome was all-cause mortality at 1 year. Efficacy outcomes were changed in New York Heart Association (NYHA) class, pressure gradients, effective orifice area (EOA), EOA indexed to body surface area (EOAi) and severity of aortic regurgitation. Mean age was 77.7 years, 62.7% were female. Procedural success rate was 99.0%. The median cross-clamp and cardiopulmonary bypass times were 68.0 and 108 min. Perceval size  Surgical aortic valve replacement (SAVR) remains the gold standard treatment for those patients with isolated aortic valve stenosis (AS) not suitable for transcatheter aortic valve replacement (TAVR) as well as in a variety of other clinical settings, where TAVR alone will just treat AS, but the other pathologies like coronary artery disease, atrial fibrillation, mitral valve pathology will need surgical approach . Rapid dS Valve for Extended CE Mark) study ) or median  as appropriate. All statistical analyses were performed with SAS software . Perioperative events were defined as those occurring on the day of implant, while early and late events were the ones occurring ≤ 30 days or > 30 days post implant, respectively.2. The mean Society of Thoracic Surgeons (STS) score and EuroSCORE II-predicted mortality rates were 5.2 ± 3.9% and 4.3 ± 5.7%, respectively. The most prevalent coexisting conditions were coronary artery disease (30.9%), heart failure (28.9%), and atrial fibrillation (15.7%). Fifty-nine patients (28.9%) had previously undergone cardiac interventions. Most of the patients (96.6%) were undergoing AVR for degenerative disease.Patient baseline characteristics are shown in Table S valve (19−21 mm) and 37.3% with a size M (21−23 mm) valve. Median pump time was 108.0 [82.5–147.3] min and cross-clamp time was 68.0 [54.0–96.5] min. Procedural success was achieved in 99.0% (202/204) of patients. In one patient implanted with an XL valve, the device was removed after aortic cross-clamp removal due to its suprannular migration, which resulted in severe PVL. The reason for this migration was the wrinkling of the aortic wall in Valsalva sinuses, which was noted after the second cross-clamp inspection. In fact, the combination of thin aortic walls, typical of Japanese patients, and an excessive traction on guiding sutures during implantation pulls the aortic annulus upward and creates wrinkles. These wrinkles to our knowledge are not uncommon in Japanese patients with thin, pliable and noncalcified aortic walls, even though we believe this can happen also to patients of different nationalities.Procedural data are shown in Table S valve, procedural failure was due to stent infolding related to valve oversizing, resulting in moderate-to-severe PVL. Both patients underwent conversion to conventional valves. All the patients were on antiplatelet or antithrombotic treatment for 3 months after surgery, according to the Japanese guidelines.In the second patient, implanted with an At hospital discharge, no moderate or severe leakages were identified, and same results have been reported at 1 year, and during the 6 month follow-up.2 before surgery to 1.5 cm2 at discharge and remained largely unchanged at 1 year  Fig. . Mean prear Fig. . Mean leAdverse events are detailed in Table One patient underwent reoperation for valve thrombus at 19 days and died 36 days after implantation. Eight additional patients died after implantation during follow-up: 1 patient diagnosed with ileus and pneumonia died 33 days after implantation; 1 patient diagnosed with end-stage lung cancer died 122 days after implantation; 1 patient died for brain infarction after 85 days, 1 patient died for aspiration pneumonia after 49 days while 4 patients died of an unknown reason which was not related to the procedure or device. The Kaplan-Meier survival curve to 12 months is shown in Fig. S, 3 with size M, 3 with size L and 1 with XL size.New onset of the complete atrioventricular block was reported in 8 patients and second-degree atrioventricular block in 1 patient. All 9 patients (4.4%) underwent permanent pacemaker implantation, two of whom had been diagnosed with pre-operative conduction disturbances at baseline. In three cases oversizing was identified as the leading cause of the atrioventricular block, bicuspid type I was present in four cases, while in one patient there was an extensive decalcification of the left ventricular outflow tract due to calcification of the mitral-aortic continuity. Among the 9 patients, 2 have been implanted with Perceval valve size The primary findings in this initial Japanese clinical experience were that (1) 1-year outcomes of SAVR with the Perceval valve in Japanese patients were favorable, also in patients with small anatomy. (2) Low PPI rate and no moderate or severe PVL were achieved by the complete decalcification using CUSA and by the selection of the proper sized valve.Sutureless valves represent an innovative approach for SAVR, allowing for faster implantation compared with sutured and conventional valves, thus reducing cardiopulmonary and cross-clamp times , 11, 12.2 in this study and this is smaller than any other study. 84% of the implanted valves were S or M size, therefore, addressing annuli with a diameter < 23 mm.Few reports have been published about Perceval valve implantation in Asian populations despite in other countries including Thailand, Taiwan, and Korea and no data are available for Japan. Compared with patients in Western countries, elderly Japanese patients tend to show smaller bodies and have smaller aortic annulus diameter. In fact, the mean BSA was 1.52 ± 0.20 mS Valve Clinical Study for Chinese Registration [PERFECT] NCT03481387). The largest available published cohort is from Korea, with 121 patients  implanted between 2014 and 2019 [P = 0.15).A premarketing study has been started in China recently  and almost half were undergoing concomitant cardiac procedures in both studies (46.6% vs. 45.5%), but the rate of complications in our cohort was low in comparison . The low rates of complications may reflect the correct sizing and positioning of the valve in this Japanese population, which may be due to several factors. First, sites experienced in cardiovascular were specifically chosen for this study, although low-volume centers also participated. The proctoring approach followed in Japan was extensive, with 5 cases being proctored versus the usual 2. Additionally, proctors scrubbed in and assisted with the procedure, providing ‘hands-on’ guidance, and emphasis was placed on correct sizing and positioning. The technique of the sizing used was described previously  where itIn our Japanese study, 83.9% of the patients received a small or medium size valve versus 62.0% of patients in the Korean study  and 40.4This is an observational study subject to the limitations of such studies, including the lack of a comparison group. The study included only Japanese patients and the findings may not be representative of other populations.1-year outcomes of SAVR with the Perceval valve in Japanese patients were favorable even in patients with small anatomy. The Perceval valve offers a promising alternative to conventional biological AVR in this Japanese population.


Background: Weight loss before undergoing metabolic and bariatric surgery (MBS) has been suggested to reduce perioperative complications, although with controversial results. The objective of this study is to evaluate the impact of treatment with GLP1-R agonists (liraglutide 3.0 mg and semaglutide 1.0 mg) on preoperative weight loss and patients’ decisions regarding MBS while on a surgical waiting list. Materials and methods: One hundred and two patients on a waiting list for MBS started treatment with GLP1-RA for at least 6 months. Changes in weight at 26 and 52 weeks, the number of patients achieving >5% weight loss, and patients’ decisions regarding MBS were evaluated. Results: After 52 weeks, patients lost 16.9 ± 7.2% of weight with semaglutide 1.0 mg and 16.1 ± 5.8% of weight with liraglutide 3.0 mg. All patients lost ≥5% of initial weight, 84.7% lost ≥10%, 54.6% lost ≥15%, and 27.5% reached ≥20%. A total of 68.6% of participants were satisfied with the achieved weight loss and withdrew from the waiting list for MBS. A threshold of >15.1% weight loss had the greatest sensitivity and specificity for the final decision regarding undergoing MBS. Conclusions: Losing >15% of initial weight after 52 weeks of treatment with liraglutide 3.0 mg or semaglutide 1.0 mg during the waiting list for MBS impacts patients’ decisions regarding the final acceptance or rejection of the procedure. For variables with a skewed distribution, the Mann–Whitney U-test was used for mean comparisons. The chi-squared test was used to analyze categorical data.Continuous variables were summarized as mean ± standard deviation. Categorical variables were expressed as absolute frequencies (percentages). The Shapiro–Wilk test was used to check the normality of the variable’s distribution. Comparison between continuous variables was performed using an independent-sample p-values were reported.Repeated-measures ANOVA was conducted for each outcome using time (moment of assessment) as a within-subjects factor and group (semaglutide vs. liraglutide) as a between-subjects factor. For the moment of assessment, only baseline, 6-month, and 12-month evaluations were included due to the presence of missing values in the visits at 3 and 9 months. Mauchly’s test was used to determine whether the assumption of sphericity was met, and Leven’s test was used to assess the homogeneity of variance. When a violation of sphericity was observed, Greenhouse–Geisser-corrected The change in laboratory variables in the whole sample was compared using the Wilcoxon signed-rank test.Receiver operating characteristic (ROC) curves were calculated to evaluate the capacity of detecting patients who rejected bariatric surgery after pharmacological treatment. Youden’s index (YI) was estimated to evaluate the best cutoff points.p-value < 0.05 was considered statistically significant. All statistical analyses were performed using IBM® SPSS 26.0, JASP Team  and Jamovi (version 2.4.).A 2 = 86.07, p < 0.001).One hundred and two patients were included. The mean age was 52.88 ± 10.38 years, and 71 (69.3%) patients were women. A total of 35 patients were treated with semaglutide 1.0 mg, and 67 were treated with liraglutide 3.0 mg. As expected, the frequency of T2D was higher in the semaglutide group than in patients taking liraglutide . A significant main effect of time was observed  = 328.189, p < 0.001). The mean observed change in the percentage of weight loss is shown in t = 0.644, p = 0.522).Eighty-five (83.3%) participants completed 52 weeks of therapy. For the variable of weight, time-by-group interaction was not significant  = 0.437, 2 = 1.105, p = 0.576)  .p = 0.520). The mean percentage of weight loss, considering both drugs together, was 17.45% ± 4.93% in patients with a BMI of 35–39.99 kg/m2, 16.06% ± 6.34% with a BMI of 40–44.99 kg/m2, and 15.35% ± 8.09% with BMI > 45 kg/m2  = 0.659, 45 kg/m2 .2 = 5.15, p = 0.076 for ≥10%; X2 = 4.85, p = 0.088 for ≥15%; and X2 = 0.463, p = 0.793 for ≥20%; . Constipation was present in 16 (23.88%) cases under treatment with liraglutide, and no cases were reported with semaglutide . Conversely, diarrhea was more frequent in patients with semaglutide (6 (17.14%) vs. 1 (1.49%), X2 = 8.810, p = 0.003). Most adverse events were mild, limited in time, and did not imply treatment withdrawal.Nausea was present in 33 (32.35%) and vomiting in 8 (7.43%), with no differences between semaglutide and liraglutide . The baseline and follow-up characteristics of groups withdrawing or not from bariatric surgery plans are shown in At week 52, 70 patients (68.62%) reported their intention to abandon the waiting list for bariatric surgery, while 32 (31.4%) were willing to undergo bariatric surgery. Among patients withdrawing from the waiting list, there were two levels of certainty in the decision: 52 (51%) expressed their intention to definitely abandon the plan for surgery, while 18 (17.6%) did not exclude this possibility in the future. There were no statistically significant differences in the final decision to reject surgery plans between patients taking liraglutide  or semaglutide  (Xp = 0.001) at 6 months and 0.768 at 12 months (The AUC for the detection of the rejection decision of bariatric surgery using the percentage of weight loss was 0.752 (2 months .p > 0.05). The best cutoff in the first case was 12.13  and 15.12 in the second case . All cutoff points are shown in According to DeLong’s test, there were no significant differences between both ROC curves  and the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) described the current indications for MBS . Specifioing MBS . For thiThe pivotal clinical trial with liraglutide 3.0 mg in patients with obesity and prediabetes showed a mean percentage weight loss of 8.0 ± 6.7% after 56 weeks  and reacCurrent indications on the management of obesity suggest that at least 10% weight loss should be reached in order to significantly improve associated comorbidities. This therapeutic recommendation seems to include one of the two following definitions: (1) the ability to safely produce an average of >10% placebo-subtracted weight loss in randomized clinical trials in the majority of patients, or (2) the ability to safely produce a ≥15% weight loss in over half the patients as an adjunct to lifestyle . In our Interestingly, 68.6% of patients, who had lost around 15% of their initial body weight, decided to withdraw from the waiting list for MBS without any influence from the physician. In this regard, the threshold that best determined the highest sensitivity and specificity for the final decision to either continue with the surgical plan or drop out was a weight loss of 15.12% , although this was observed after 6 months when weight loss was above 12%. To our knowledge, this is the first time that a sustained weight loss over a period of at least 26 weeks has had such a remarkable influence on the decision regarding the planification of MBS.GLP1-receptor agonists entail significant metabolic changes beyond mere weight loss, particularly regarding the improvement in insulin sensitivity and lipid and hepatic profiles. The positive changes were also evident for individuals with type 2 diabetes, in whom the percentage of patients reaching different HbA1c goals improved.Finally, 31.4% of participants remained keen to undergo a bariatric procedure. A higher baseline BMI and a poorer response to medical treatment contributed to persisting in the decision to undergo MBS. According to the logistic regression analysis performed in our study, age, sex, or comorbidities did not influence patients’ decisions. A percentage weight loss lower than 10% and, although to a lesser extent, a higher baseline BMI were the two main factors that contributed to the decision to undergo MBS. Weight loss could not be considered insufficient in patients who maintained their decision to undergo surgery, as it was truly in the range of prior clinical trials ,33,34, aIn this setting, new drugs for the management of obesity, which are currently being evaluated in phase 3 studies, and that have proven to achieve weight loss rates above 20%, will almost reach comparable results to MBS ,41,42 anThe secondary adverse effects reported by patients in our study were similar to the ones reported in the majority of prior clinical studies. Specifically, the main complaints concerned mild- to moderate-intensity gastrointestinal issues, which were mainly transitory and did not determine the need to withdraw medication.Our study has some limitations. First, it is a single-center observational retrospective study, so the results cannot be fully transposed worldwide to what may happen in other hospitals. Second, only patients who could afford the cost of sustained pharmacological treatment were included, leaving out other patients with worse socio-economic situations. It is true that in the United Kingdom, financial support for the treatment with semaglutide 2.4 mg for 2 years may be available in patients with severe obesity , but thiHowever, we remark on the strengths of our study. Specifically, it reflects what may occur in real-world clinical practice in patients who are keen to lose weight before undergoing MBS. These patients were closely followed up in a specific outpatient obesity clinic, with the support of trained nurses and registered dietitians, which warrants high adherence to long-term follow-up and medical treatment.This study shows that a weight loss greater than 15% after one year of pharmacological treatment with GLP-1 receptor agonists may determine a shift in the decision to undergo MBS in around two-thirds of patients on a waiting list for a bariatric procedure. Promoting pharmacological treatment before MBS may help patients decide if they truly want to undergo a bariatric procedure.


Introduction: Teachers are central to the well-being of a community. Being an influential part of society, their role can be broadened to promote oral health and healthy oral hygiene habits. This study was aimed at the assessment of the oral health status and treatment needs of school teachers in Indore City.Method: A descriptive cross-sectional study was carried out over a period of five months on 470 school teachers working in various government schools of Indore city selected through random sampling technique. The modified WHO Oral Health Assessment Form for Adults 2013 was used to record oral health status and treatment needs, while the WHO Questionnaire for Adults 2013 was used to document oral hygiene practices, dietary habits, and deleterious habits. Data was analyzed using IBM SPSS Version 25 . Chi-square test, independent t-test, and one-way ANOVA were used.Results: The gender distribution of the representative sample showed female predominance. The prevalence of smokeless tobacco consumption was 5.1% among the study subjects. The mean number of Decayed, Missing, and Filled Teeth (DMFT) was 3.45 ± 3.10, and the mean number of 1.52 ± 2.40 teeth showed the presence of bleeding. Around 37.2% had shallow pockets of 4-5 mm. A mean number of 4.26 ± 1.97 sextants showed 0-3 mm attachment loss. There was a significant association between the frequency and technique of toothbrushing with a decayed number of teeth (p<0.001).Conclusion: High proportion of dental caries and periodontal disease was seen which could be related to their oral health care-seeking behavior and the impairment related to age changes. Education is the greatest wealth earned by anyone and Teachers’ are considered the fountain of knowledge. India has a deep-rooted history in the field of Education and has a long tradition of giving special status to teachers. As teachers are the primary source of education, health education, healthful living, a healthy environment, and oral health as well, they are the flag bearer for health-promoting activities . They unAccording to United Nations International Children's Emergency Fund (UNICEF), more than 1.5 million schools, 8.5 million teachers, and 250 million students from diverse socioeconomic backgrounds make up the Indian Education System . It coulThere is ample literature available measuring the Oral Health Related Knowledge, Attitude and Practice of School Teachers -7. But tA descriptive cross-sectional study was conducted to assess the oral health status and treatment needs, oral hygiene, dietary and deleterious habits among the government school teachers of Indore city. The study ran from May 2022 to September 2022, lasting for a total of five months. Schools included were from both urban as well peri-urban areas of Indore City.Ethical approval was obtained from the Institutional Ethics Committee at the Government College of Dentistry, Indore. Permissions were attained from the District Education Officer (DEO) for Indore District. Informed consent was obtained from the study subjects before the commencement of the study.The study included school teachers who provided their consent to participate, as well as those who were employed in the school for at least one academic year and were present during the study period. The teachers who did not give their consent to participate in the study were unavailable during the study period, or who were employed as visiting staff were excluded from the study.Sample size estimation2P (1-P)/d2, where Z is the standard normal variate, P is the expected prevalence and d is the absolute error or precision. The sample size calculated was 462, rounded off to 470 samples.A pilot test was conducted among 30 school teachers in Indore city, in which the prevalence of Dental Caries was found to be 76.6%. The relative precision of 3.83% and proportion 76.6% were incorporated into the formula for sample size calculation for cross-sectional study, that is, n = Zhttps://www.random.org/) to select the schools from the list acquired. The random numbers were generated and corroborated with assigned numbers for schools from the list. Instruments mentioned in WHO Basic Oral Health Survey 5th edition were used, including Mouth Mirror and Community Periodontal Index (CPI) Probe.Simple random sampling was performed using an online random generator tool (Coronavirus disease 2019 (COVID-19) infection control protocolCOVID-19 Infection Control Protocol was followed during the clinical examination and data collection procedure.Data collectionData was collected using the WHO Oral Health Assessment Form for Adults. An oral health examination of type III was conducted by an examiner trained and evaluated by VS on a group of 10 patients visiting the Department. The inter-examiner and intra-examiner reliability scores of 0.87 and 0.89 respectively indicated substantial agreement.Additional information regarding oral hygiene habits, dietary habits, and deleterious habits was assessed using the self-administered modified WHO Oral Health Questionnaire for Adults 2013, which is a pre-tested, pre-validated, structured questionnaire. It included questions on the type of oral hygiene aid used (toothbrush and toothpaste/finger/stick/other) frequency of brushing (once/twice/more than 2 times), the technique of brushing , use of fluoridated toothpaste (yes/no/don’t know), tobacco consumption (yes/no) and its form (smokeless/smoke/both) and frequency of intake of specified food items.The study subjects were imparted individualized oral health education and an appropriate referral system was in place for people requiring dental treatment.Statistical analysisThe data obtained was entered into Microsoft Excel 2016 and descriptive and inferential statistical analysis was performed using IBM SPSS Statistics for Windows, version 25  software. Categorical variables were analysed by Chi-square test and continuous variables by One-Way ANOVA. The association between the variables was analysed using an independent t-test and One-Way ANOVA. The confidence interval was fixed at 95%, and α error was set at 5%. A p-value <0.05 was considered statistically significant.The current descriptive cross-sectional study reveals the oral health status and treatment needs of school teachers in Indore City. The representative sample was stratified into four age groups of 21-30 years, 31-40 years, 41-50 years, and 51-60 years. The age ranged between 21 and 60 years, with a mean age of 45.32 ± 9.29. Gender distribution revealed 152 (32.3%) teachers were male and 318 (67.7%) teachers were female. The prevalence of smokeless tobacco consumption was 5.1%. All the teachers used toothbrushes and toothpaste. Most of them brushed once a day (72.1%) while 27.9% brushed twice a day. Of the total sample, 35.3% of the representative sample used fluoridated toothpaste, 33.2% did not use fluoridated toothpaste and 31.5% did not know about fluoridated toothpaste  was 82.1%, which showed an increasing trend with an increase in the age group. The prevalence of fluorosis was found to be 2.7% and showed statistically significant differences across the age groups (p<0.001). The prevalence of dental erosion was 3.4%. Around 10.1% showed signs of dental traumatic injuries, of which enamel fracture was the highest (3.2%). The prevalence of oral mucosal lesions was 3.6% and included cases of abscess, oral submucous fibrosis, and koplick spots. Regarding prosthetic status, 1.7% had upper partial dentures and 1.9% had lower partial dentures. The intervention urgency showed that prompt treatment was required by 58.1% of study subjects, followed by preventive or routine treatment (38.9%)  among the representative sample was 3.45 ± 3.10 which showed statistically significant differences across the age groups (p<0.001). The prevalence of shallow pockets was found to be 37.2% and deep pockets were 4.9%. A mean number of 1.20 ± 2.50 and 0.12 ± 0.71 teeth presented with shallow and deep pockets, respectively. The mean number of 4.26 ± 1.97 sextants showed 0-3 mm and 1.50 ± 1.70 sextants showed 4-5 mm attachment loss. A mean number of 0.08 ± 0.37 sextants showed 6-8 mm attachment loss  was 3.45 ± 3.10 in which the filled component contributed significantly indicating escalated oral health care-seeking behavior among school teachers. The prevalence of decayed teeth and mean Decayed, Missing and Filled Teeth (DMFT) in the current study was lower than that reported by Mary et al.in Chennai, India . HoweverPeriodontal status is a direct reflection of oral hygiene practices, which were not found to be practiced fittingly among the study subjects. Gingival bleeding was present among very few study subjects signifying accumulation of chronic condition. The prevalence of shallow periodontal pockets was 37.2% and the mean number of teeth affected was 1.20 ± 2.50, which shows the cumulative effect of the periodontal condition. This was higher than reported by Swamy et al. . Since pAround 9.1% of school teachers suffered from traumatic injuries to teeth due to accidents and sports injuries. About 2.1% of treated injuries show the vigilance of school teachers towards utilizing dental care treatments, often accessible and affordable by them.The prevalence of fluorosis in our study was found at 2.7%, with the majority (2.3%) in ‘very mild’ category. Since the teaching profession involves frequent transfers, especially in the government sector, the prevalence of fluorosis could be due to migratory reasons. The presence of fluoride belts in Madhya Pradesh could also explain the present prevalence of fluorosis .The current study showed a prevalence of 3.6% of oral mucosal lesions. The findings were higher than that reported in Chennai . The finThe prosthetic status in a population signifies the oral health treatment-seeking habit and the awareness to utilize the provision of dental services. In the present study, 1.7% and 1.9% of the teachers had upper and lower removable partial dentures respectively. This could be because our population comprised of society’s educated segment and hence oral health care seeking was high among them. Our findings are in concordance with other similar studies -14.The need for preventive or routine treatment was 38.9% while 58.1% required prompt treatment, which reveals a lack of mindset due to unawareness regarding appropriate knowledge of oral health. Immediate or urgent treatment was indicated for 3% of the examined study sample due to silent non-symptomatic morbid conditions. Since the majority of school teachers overlook on importance of oral health, the preventive treatment for optimum oral health stands trivial. Only symptomatic treatment was pursued and given importance by them as subjected to disruption of routine. Consequently, the need for prompt and preventive treatment for oral health promotion among the representative sample needs to be addressed on prime precedence. The findings are in concordance with the intervention urgencies reported by other studies .The study recommends the implementation of the Teachers Training Program as formulated by the Dental Council of India in their Publication “Training Manual on Oral Health Promotion for School Teachers” . The rolThe present study revealed that the study subjects showed an overall oral health status with mixed results. While the caries experience was high among the sample, it also included a high proportion of filled teeth, which is a positive sign of their oral healthcare-seeking habits. The prevalence of gingival and periodontal disease necessitates the provision of promotive, preventive, and curative oral health care services for school teachers. In an effort to target the oral health of the school community by taking a holistic course of action, it is imperative that oral hygiene knowledge and associated practices be alleviated among the school teachers. Our results were found to be in concordance with other studies conducted in various parts of India on school teachers.


Patients had median of one prior therapy line (range 0–11). Median treatment duration with idelalisib was 5.1 months (range 0–55.0 months). Of 58 patients with documented treatment outcome, 39 responded to idelalisib containing therapy (67.2%). Patients treated with the BTKi ibrutinib as last prior treatment prior to idelalisib responded in 71.4% compared to a response rate of 61.9% in patients without prior ibrutinib. Median event free survival (EFS) was 15.9 months with a 16 versus 14 months EFS in patients with ibrutinib as last prior treatment or not, respectively. Median overall survival was 46.6 months. In conclusion, treatment with idelalisib appears to have a valuable impact in patients being refractory to prior ibrutinib therapy even though there are limitations in our analysis due to the low number of patients included.Idelalisib in combination with rituximab is an efficacious treatment for patients suffering from chronic lymphocytic leukemia (CLL) with known limitations due to toxicities. However, the benefit after prior Bruton tyrosine kinase inhibitor (BTKi) therapy remains unclear. For this analysis, 81 patients included in a non-interventional registry study of the German CLL study group (registered at  In 2016, serious side effects and an increased fatality rate were documented in ongoing clinical trials, so that further safety measurements were implemented and application in first-line therapy was restricted.The oral first-in-class phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor idelalisib in combination with the CD20-antibody rituximab has been approved for therapy of chronic lymphocytic leukaemia (CLL) back in 2014 and is indicated for the treatment of patients with at least one prior therapy or first-line treatment in presence of Efficacy of idelalisib in combination with rituximab is proven in heavily pre-treated patients with CLL , 2. EvenHowever, it remains unclear which patients may benefit the most from the combination and how the drug is rated in different treatment lines. Furthermore, the benefit of idelalisib containing therapy is unclear after prior treatment with the Bruton Tyrosin Kinase Inhibitor (BTKi) ibrutinib.www.clinicaltrials.gov as #NCT02863692.In this non-interventional registry study of the German CLL Study Group (GCLLSG) all patients with a confirmed CLL, irrespective of treatment regimens as well as therapy line including watch and wait patients, can be included and are followed until death. Patients were managed in outpatient hematological departments, peripheral hospitals as well as in academic centers. Data on status of the disease and treatment if applicable (including duration of treatment) were collected at least annually. Patient demographics, including cytogenetic aberrations and IGHV gene status, were collected at time of first diagnosis and start of each line of treatment. The primary endpoint of the registry is overall survival (OS), secondary endpoints include event-free survival (EFS) and time to next treatment (TTNT), overall response rate (ORR) of all treatment lines, secondary diseases such as secondary malignancies, autoimmune diseases and infections, course of the disease in predefined biological subgroups as well as the quality of life. The registry was approved by all involved Ethic committees according to the declaration of Helsinki and German physicians’ professional regulation. All patients provided informed consent. The registry is registered at This analysis considers all patients included in the above mentioned GCLLSG registry study meeting the predefined criteria of a confirmed diagnosis of CLL and being treated at least one time with idelalisib containing regimens ; however, patients participating in a clinical trial of the GCLLSG evaluating idelalisib  were exPatient, CLL and treatment characteristics including ORR and treatment duration, which was defined as the time between start and stop date of treatment , were reported using counts and percentages for categorical variables and descriptive statistics for continuous variables. For demographics and CLL characteristics, values at start of first idelalisib treatment were used.EFS was defined as the interval between start of treatment and disease progression, start of next treatment or death of any cause. TTNT was calculated from start of treatment to start of next therapy and OS from start of therapy to death.Time-to-event endpoints were analyzed from start of last therapy prior first idelalisib therapy, from start of first idelalisib treatment, and from start of first subsequent treatment after first idelalisib therapy using Kaplan–Meier methods.Analyses were done using SPSS version 26.For this analysis, 4994 patients that were included at the timepoint of June 2020 in the registry of the GCLLSG were considered. 81 patients from 36 sites in Germany met the predefined criteria and were included in the analysis population of this study. 11 patients were still on first idelalisib containing therapy at the timepoint of the data cut-off. The median observation time from start of first-line therapy was 109.7 months (range 2.6–254.4 months).Patient characteristics are shown in Table 33 patients received further therapy after termination of idelalisib treatment. Therapy sequence is shown in Fig. The median time from first diagnosis until the start of first idelalisib containing therapy was 80.5 months (range 1.2–278.3 months). All 81 patients received idelalisib in combination with rituximab. Treatment was most frequently  started in 2015 . However, one patient started therapy in 2013 (1.2%), 13 patients in 2014 (16.0%), 16 patients in 2016 (19.8%), 13 patients in 2017 (16.0%), 11 patients in 2018 (13.6%) and 2 patients in 2019 (2.5%), respectively. 70 patients received prior CLL therapy before administration of idelalisib whereas A median of one prior therapy was administered before start of the idelalisib containing therapy (range 0–11). Eleven patients received idelalisib as first-line therapy (13.6%), 32 patients as second-line (39.5%) and 14 patients as third-line treatment (17.3%). Twenty-four patients received ≥ 3 prior therapies (29.6%).With 46.9% of all administered treatment regimens, bendamustin containing therapies were most commonly given as prior therapy. Venetoclax constituted 1.1% of the prior therapies whereas ibrutinib containing regimens were administered in 7.4%.Fifty-nine of 70 pretreated patients (84.3%) did not receive ibrutinib before start of idelalisib therapy. One patient was treated with ibrutinib as any other prior therapy (1.4%) whereas 10 patients had ibrutinib as the last prior treatment before idelalisib (14.3%).Eleven patients (13.6%) received idelalisib plus rituximab as first-line treatment, 1 patient ibrutinib (1.2%) and 69 patients (85.2%) chemotherapy with or without rituximab. As chemoimmunotherapy, bendamustin plus rituximab was most commonly given in 32 patients (39.5%). The median EFS from start of first-line treatment was 31.7 months with a one-year survival of 82.6%, a 3-year-survival of 42.6% and a 5-year-survival of 13.8%. Progressive disease (PD) after start of first-line therapy is documented in 58 patients of the analysis population. In 32 patients (55.2%), the time between start of first-line treatment and PD was ≤ 36 months and in 26 patients (44.8%) > 36 months.Response to last treatment prior to first idelalisib therapy summarized in Table Forty-one of 57 patients with documented response assessment for last treatment prior to idelalisib therapy responded (71.9%) and 16 patients did not respond (28.1%).The median time to first idelalisib containing therapy from start of last prior treatment was 22.3 months. For patients with ibrutinib as last prior treatment, median time was 8.1 months, for the patient with ibrutinib as any other prior treatment 5.7 months and for patients without prior ibrutinib therapy 29.0 months.The median EFS form start of last treatment prior to first idelalisib containing therapy was 19.6 months. For patients with ibrutinib as last prior treatment median EFS was 8.4 months, for the patient with ibrutinib as any other prior treatment 5.7 months and for patients without prior ibrutinib therapy 27.4 months.Median OS from start of last treatment prior to first idelalisib containing therapy was not reached with a 3-year survival of 80.7%. For patients with ibrutinib as last prior treatment median OS was not reached with a 3-year survival of 77.8%. For the patient with ibrutinib as any other prior treatment OS was 9.2 months whereas the median OS for patients without prior ibrutinib therapy was not reached with a 3-year survival of 82.5%.Median treatment duration with first idelalisib containing regimen was 5.1 months (range 0.0—55.0 months), while the median treatment duration was 2.8 month (range 1.0–36.1 months) in patients with idelalisib containing regimen as first-line therapy.For 58 patients, information about treatment outcome is available; 39 patients (67.2%) responded, 19 patients did not respond (32.9%). Information about treatment outcome is missing in 23 patients (28.4%). Seven of 11 patients who received idelalisib plus rituximab as first-line therapy responded. Information is missing for 4 patients.Five of 7 patients with ibrutinib as last prior therapy responded to idelalisib (71.4%). Information is missing for 3 patients. In contrast, the patient with ibrutinib as any other prior therapy did not respond and 26 of 42 patients without any prior ibrutinib therapy responded (61.9%). Information is missing in 17 patients.del17p  and all patients with TP53 mutation  responded. For the latter, information is missing in 1 patient. In contrast, 9 of 12 patients without del17p (75.0%) and 6 of 7 patients without TP53 mutation (85.7%) responded. Information is missing in 4 and 0 patients, respectively. Taking these high-risk features together again, all patients with del17p and/or TP53 mutation responded . Information is missing in 1 patient. Concerning 7 patients with neither del17p nor TP53 mutation, 6 patients responded (85.7%).Furthermore, all patients with With regard to the number of prior treatment lines, 29 of 33 patients with ≤ 1 prior treatment (87.9%) responded whereas the response rate was 20% in 10 patients with 2 prior treatment lines and 53.3% in 15 patients with ≥ 3 prior therapies. Information is missing in 10, 4 and 9 patients, respectively.TTNT is shown in Fig. Median TTNT was 28.0 months after start of first idelalisib containing regimen with a 6-months survival of 90.6%, a 12-months survival of 77.5% and a 24-months-survival of 50.9%.According to the number of administered treatments prior to idelalisib therapy, median TTNT was 29.0 months in patients with ≤ 1 treatment, 12.9 months in patients with 2 treatments and 28.0 months in patients with ≥ 3 treatments.EFS is shown in Fig. Median EFS was 15.9 months after start of first idelalisib containing regimen with a 6-months survival of 76.7%, a 12-months survival of 58.6% and a 24-months survival of 30.2%.OS is shown in Fig. 29 of 81 patients (35.8%) died. Causes of death included 10 PD (34.5%) including two patients with Richter’s transformation (RT) and one patient whose death was additionally caused by progressive myelodysplastic syndrome. One fatality (3.4%) was a pneumonia and deemed as treatment related. Besides this, 4 cases of infections (13.8%) including 2 cases of pneumonia, 2 cases of concomitant diseases  and 4 cases of other malignancies  were documented as causes of death. For 8 patients the reason for death is unknown.Median OS was 46.6 months after start of first idelalisib containing regimen with a 6-months survival of 90.9%, a 12-months survival of 83.8% and a 24-months survival of 77.3%.Three patients (3.7%) achieved RT after start of first idelalisib containing regimen. These patients were pretreated with chemoimmunotherapy before administration of idelalisib.Fifty-six subsequent treatment regimens were administered in 33 patients after first idelalisib therapy. Ibrutinib- (37.5%) and venetoclax-containing regimes (21.4%) were administered most frequently. Stem cell transplant was performed in 7.1%. Further therapies consisted of chemo- or chemoimmunotherapy. Additionally, ibrutinib-containing regimens were the most frequent first subsequent therapy after idelalisib containing therapy (48.5%). For 20 patients the response of the first subsequent therapy is documented with 10 patients (50%) responding.48 patients did not receive subsequent therapy after first idelalisib containing regimen. Of these, 20 patients died (41.7%). Eight patients died due to progressive disease (40.0%), including two patients with RT One death was a pneumonia and deemed as treatment related (5.0%). Three death cases were related to infections (15.0%), including 2 patients with pneumonia, and 4 patients died due to other malignancies (20.0%), including one patient with metastatic bronchial, metastatic urothelial carcinoma, squamous cell carcinoma, and oesophagus carcinoma each. For 4 patients the cause of death is not known.28 patients without subsequent therapy after first idelalisib containing regimen were still alive. Of these, the median treatment duration in 17 patients with discontinued idelalisib therapy was 5.1 months (range 1.7–17.9 months) whereas the median treatment duration in 11 patients with ongoing idelalisib therapy was 12.7 months (range 0.0–55.0 months).Median EFS after start of first subsequent treatment following first idelalisib containing regimen was 10.7 months with a 6-months survival of 75.0%, a 12-months survival of 47.5% and a 24-months survival of 38.4%.Median OS after start of first subsequent treatment following first idelalisib containing regimen was 46.7 months with a 6-months survival of 100.0%, a 12-months survival of 92.3% and a 24-months survival of 78.4%.With this real-world analysis of patients being documented in the registry of the GCLLSG we aimed to evaluate the outcome of idelalisib containing therapies in patients with CLL, especially after prior treatment with the BTKi ibrutinib.With an ORR of 67.2% and a 12-months OS of 83.8% our data seem inferior compared to what was described in clinical trials testing idelalisib plus rituximab with an ORR of 81% and a 12-months OS of 92% [As only progression-free survival (PFS) rather than TTNT or EFS is described in other real-world studies including idelalisib, our data are also difficult to compare to these studies. However, response rates are lower and OS seem to be shorter in our analysis , 6, evenThough, we wanted to raise the question if there is still a value for using idelalisib in the progressing treatment landscape of CLL. As the declining use of the drug over the years shows, the application of idelalisib is already small. However, there might be a group of patients that benefit from treatment with idelalisib containing regimes. With a response rate of 42.9% and a median TTNT of only 8.1 months in patients with ibrutinib as last prior treatment prior to idelalisib, it must be assumed that these patients were almost refractory to treatment. Notably, 71.4% of these patients responded to idelalisib with a median EFS of 16.0 months. This underlines the potential value of the drug as bridging therapy to definite therapies such as CAR-T-therapy in the future or allogeneic stem cell transplant for eligible patients.The main limitation of our analysis is the small number of patients that were included. Hence, especially the validity of subgroup analyses is limited. Furthermore, we neither can conclude on the reason for the relatively short treatment duration nor on the type of adverse events that probably led to treatment discontinuation, because these data are not collected in the German CLL study group registry. The question, whether there is a place for idelalisib or other PI3K inhibitors in CLL treatment, particularly in patients who were refractory to BTK inhibitors or venetoclax, cannot be answered with our data, because most of the patients were not treated with targeted agents but with alkylating agents before their treatment with idelalisib. Therefore, these patients do not reflect the current population of CLL patients. Due to novel, promising drugs that are introduced in the treatment of CLL recently, such as non-covalent BTK-inhibitors or bispecific antibodies, the value of idelalisib salvage treatment will remain limited to few patients.


Menopause is a special period for women which can have both physical and psychological consequences.The aim of our study was to assess the impact of menopause on women’s quality of life.A cross-sectional descriptive study conducted on menopausal women consulting at the basic health center in réjiche over a period from 12 september to 12 october 2022. The impact of menopause on the mental health of women was assessed by the menopause rating scale (MRS).A total of 83 women were incluted in our study. The mean age was 61.89±11.03 years. The median age of menopause was 45 years (50-43). The majority of women (90.4%) were married and five women (6%) lived alone. Twenty-six women were professionally active and more than half were sedentary (54.2%). The comorbidities were dominated by arterial hypertension (50.6%). The mean BMI was 30.6±4.75 Kg/m². All the women had a variable psychological impact (from minor to very strong). The median score of the psychological scale was 10 (13-7): median scores for depressed mood, anxiety and physical and intellectual fatigue equal to 3 (4-1), each and median score for irritability equal to 2 (4-1). Physical and mental fatigue was the most common psychological symptom in 88% of cases followed by irritability in 86.7% of patients. Depressive and anxious symptoms were noted in 85.5% and 84.3% of cases, respectively. Psychological impact was severe in 33.7% of patients (strong or very strong symptoms).Focusing on a small sample of menopausal patients, our study revealed a high prevalence of psychological distress during menopause which requires early adequate assessment and treatment.None Declared


The World Health Organization recommends that Assisted Reproductive Technology be complementary to other ethically acceptable solutions to infertility. Whereas fertility centres are increasing in number in urban regions of Africa, published reports of their performance are sparse. We present a 10-year review of assisted reproductive technology performed in a public tertiary centre in Lagos, Nigeria.p < 0.05.This was a hospital-based, retrospective, cross-sectional review of 604 women, over a 10-year period that had in-vitro fertilization or in-vitro fertilization with intra-cytoplasmic sperm injection at the Institute of Fertility Medicine, Lagos State University Teaching Hospital. Data obtained were expressed in descriptive statistics and Pearson correlation was used to determine the strength of linear relationship between two continuous variables at a significance level of r = 0.306, p < 0.001); weak negative correlation between age and serum anti-mullerian hormone  and very weak correlation between body mass index and serum follicle stimulating hormone . In-vitro fertilization and intra-cytoplasmic sperm injection was the method of fertilization used in 97.4% of the cases and 81.8% of embryos formed were of good quality. Most women (94.5%) had 2 embryos transferred and 89.9% had day-5 embryo transfer done. About 1 in 4 of the women  had clinical pregnancy and 49.7% of women who got pregnant had delivery of a live baby at term while 11.9% had preterm delivery of a live baby.The mean age of the women was of 37.7 ± 6.2 years and 89.7% had no previous parous experience. About 27.2% of the male partners had normal seminal fluid parameters while 4.6% had azoospermia. Median serum follicle stimulating hormone of the women was 8.1 IU/L and median serum anti-mullerian hormone was 6.3 pmol/L. There was weak positive correlation between age and serum follicle stimulating hormone (Despite increasing use and success of assisted reproductive technology in south-western Nigeria, there is room for improvement in clinical pregnancy rates and live birth rates post- assisted reproductive technology. Complication rates are desirably low. Infertility in low- to middle- income countries(LMICs) is a major health problem with consequent negative psycho-social impact especially more on the affected woman. It remains a matter of public health importance that does not get the attention it deserves . The oveThe leading causes of infertility in LMICs are male factor and tubal disease secondary to sexually transmitted infections, unsafe abortion and complications of childbirth . Tubal fIt is encouraging that the number of centres performing assisted reproductive technology in Africa is gradually increasing. However, published reports on large groups of couples accessing ART and its success rates in this region are sparse , 6. CurrThis was a retrospective, cross-sectional review, over a ten-year period, of 604 women that accessed artificial reproductive technology (ART) on account of infertility at the Institute of Fertility Medicine, Lagos State University Teaching Hospital, Lagos, Nigeria. Source of referral included the gynaecology clinic of the study institution, public, private, secondary and tertiary health facilities.The medical records of couples desirous of conception who presented at the study location for assisted conception between January 2012 and January 2022, were reviewed for relevant study data. Women older than fifty-five years seeking ART during the study period were excluded.Data obtained were age, religion, parity, ethnicity, regularity of menstrual cycle, number of children alive, weight, height, body mass index (BMI), stimulation protocol used, number of cycle attempt at oocyte retrieval, method of fertilization (IVF or IVF/ICSI), quality of embryo used, type of endometrial preparation before transfer, number and grade of embryo transferred, sperm quality, gamete used (use of donor for sperm and/or oocyte) and ART outcome.Assisted reproductive technology (ART) refers to all treatments or procedures that include the in vitro handling of human oocytes and sperm or embryos for the purpose of establishing a pregnancy. This includes, but is not limited to, in vitro fertilization and embryo transfer, gamete intrafallopian transfer, zygote intrafallopian transfer, tubal embryo transfer, gamete and embryo cryopreservation, oocyte and embryo donation and gestational surrogacy. ART does not include assisted insemination  using sperm from either a woman’s partner or sperm donor .Agonist long protocol used involves daily administration of GnRH agonists like Buserelin commenced on day twenty-one or a week before the next menstrual flow and continued for four to five weeks. This is down regulation. Then ovarian stimulation with FSH or hMG (75 IU to 250 IU depending on patient characteristics) for twelve to fourteen days. Trans-vaginal ultrasound monitoring of follicular growth is done every three to four days. Ovulation trigger is done at follicular size of 18 mm and above. Egg collection is ensured by thirty-six hours of the ovulation trigger.Agonist short protocol involves ovarian stimulation commenced on day two of the cycle and commences buserelin from the fourth day of stimulation and may last between twelve to fourteen days. Transvaginal ultrasound for follicular size monitoring is done three to four days. The trigger is also done thirty-six hours before egg collection.For antagonist protocol, ovarian stimulation with FSH or hMG is started on the second to fifth day of the menstrual cycle and GnRH antagonist (Cetrotide) is commenced when the follicular size is about 14 mm. Trigger is done with Buserelin to stimulate the final follicular maturation prior to oocyte retrieval.Day-3 embryos were graded using three criteria: (I) Number of cells; (II) Symmetrical arrangements  and (III) Fragmentation .Embryo grading on day 5 was done using three criteria: (I) Thining/ Expansion of the zona pellucida and liquid cavity ; (II) Inner cell mass (ICM) grows into the foetus  and (III) Trophectoderm develops into the placenta .The following embryos were classified as good quality embryo: 3AA, 4AA, 5AA, 6AA, 3AB, 4AB, 5AB, 6AB, 4BA, 5BA, 6BA, 3BB, 4BB, 5BB and 6BB while poor quality embryo included those with grades 4BC, 5BC, 6BC, 4CB, 5CB or 6CB. Clinical pregnancy in this study is defined as evidence of pregnancy by clinical or ultrasound parameters  . Multiplp < 0.05 significance. This study was performed in accordance with the principles stated in the Declaration of Helsinki. Ethical approval for the study was obtained from the Health Research and Ethics Committee of the Lagos State University Teaching Hospital (LASUTH) with protocol number LREC/06/10/1887.The data obtained were entered and analysed using IBM Statistical Product for Service Solutions (SPSS) version 22. Data was expressed in proportions, mean and median. Pearson correlation was used to determine the strength of linear relationship between two continuous variables. For all statistical tests, a confidence level of 95% was used with More than two-third (68.7%) of the women who had ART were aged 35 years and above and the mean age of the women who had IVF or ICSI was of 37.7 ± 6.2 years. Nine in ten (89.7%) of the infertile couples had no previous parous experience and 91.6% had no living child at the time of their presentation for ART (Table 2(4.9) and 27.0 kg/m2(24.1–30.5), serum FSH (IU/L) was 10.6(11.4) and 8.1(6.6–10.1), serum AMH (pmol/L)was 17.4(52.5) and 6.3(1.4–17.6), serum estradiol (pmol/L) 28.8(78.2) and 7.4(2.4–10.0) and post ovulation endometrium thickness 8.6 mm(9.2) and 7.5 mm(7.5–9.5) respectively (Table For women who accessed ART in this study the mean (SD) and median (IQR) of their body mass index was 27.3 kg/mr = 0.306, p < 0.001); weak negative correlation between age and serum AMH  and very weak correlation between BMI and serum FSH   endometrial preparation done before embryo transfer (Table Less than 1% of the women who had ART developed ovarian hyper stimulation syndrome (OHSS) (0.7%) or ectopic pregnancy (0.3%). About 1 in 4 of the women  had clinical pregnancy and 49.7% of women who got pregnant had delivery of a live baby at term while 11.9% had preterm delivery of a live baby Table .Table 5This is an overview of findings from data of couples who had assisted reproductive technology in a Nigerian teaching hospital over a 10-year period. More than two-third 68.7%) of the women who had ART were aged 35 years and above and the mean age of the women who had IVF or ICSI was of 37.7 years. Orhue et al. in a similar retrospective observational study of 600 couples, who underwent IVF at University of Benin Teaching Hospital over a 5-year period, also reported a mean age of 36.7 ± 4.3 years .7% of th noted thOf these women who had IVF or ICSI done at our Institute of Fertility Medicine, nine in ten 89.7%) of the infertile couples had no previous parous experience and 91.6% had no living child at the time of their presentation for ART. Orhue et al. also noted that most of the women (82.4%) in their study were nulliparas [9.7% of tAssessment of male partners in this study revealed that 27.2% had normal seminal fluid parameters, 67.7% had oligospermia and 4.6% had azoospermia. Owolabi et al. in Ile-Ife, Nigeria also found a high rate of abnormal semen quality of male partners of infertile couple with oligozoospermia, teratozoospermia, asthenozoospermia and azoospermia in 25.6%, 18.5%, 11.5% and 6.2% respectively in their study participants . AdewunmWe observed that though significant, correlation between age and serum FSH was weak and positive while weak negative correlation existed between age and serum AMH. Correlation between BMI and serum FSH was very weak. Our findings on the relationship between these markers of ovarian reserve and age is similar to those of Bozkurt et al. who noted that age positively correlated with basal FSH and inversely correlated with AMH . Age is Less than 1% (0.7%) of the women who had ART developed OHSS. Schirmer et al. in the United States noted a current OHSS rate of 0.53% following IVF cycles . Our OHSIn this review the ectopic pregnancy rate was 0.3%. Ishihara et al. reported that there was no ectopic pregnancy in treatment outcomes of registered fresh cycles in assisted reproductive technology in Japan in 2017 . In vitrAbout 1 in 4 of the women  during the period of review had clinical pregnancy and 49.7% of women who got pregnant had delivery of a live baby at term while 11.9% had preterm delivery of a live baby. The pregnancy rate of 23.7% per cycle in this review is comparable to the pregnancy rate per embryo transfer of 23.0% for IVF and 19.2% for ICSI in Japan . The EgyWe observed a miscarriage rate of 37.8%, multiple pregnancy rate of 0.7%, preterm live baby rate of 11.9% and term live baby rate of 49.7%. Dimanlig-Cruz et al. in a Canadian population-based study found that crude cumulative incidences of adverse pregnancy and birth outcomes, except for small gestational age, were highest in ART pregnancies . They obOnly 0.3% of our study population had frozen embryo used during their ART. This very low rate was because capacity to freeze embryos was not available until the tail-end of the study period. We noted that Zhu et al  had inteDespite increasing use and success of ART in south-western Nigeria, there is room for improvement in clinical pregnancy rates and live birth rates post-ART. However, complication rates following ART are desirably low.


Delayed puberty (DP) is a frequent concern for adolescents. The most common underlying aetiology is self-limited DP (SLDP). However, this can be difficult to differentiate from the more severe condition congenital hypogonadotrophic hypogonadism (HH), especially on first presentation of an adolescent patient with DP. This study sought to elucidate phenotypic differences between the two diagnoses, in order to optimise patient management and pubertal development.This was a study of a UK DP cohort managed 2015-2023, identified through the NIHR clinical research network. Patients were followed longitudinally until adulthood, with a definite diagnosis made: SLDP if they had spontaneously completed puberty by age 18 years; HH if they had not commenced , or had commenced but not completed puberty , by this stage. Phenotypic data pertaining to auxology, Tanner staging, biochemistry, bone age and hormonal treatment at presentation and during puberty were retrospectively analysed.78 patients were included. 52 (66.7%) patients had SLDP and 26 (33.3%) patients had HH, comprising 17 (65.4%) pHH and 9 (34.6%) cHH patients. Probands were predominantly male (90.4%). Male SLDP patients presented with significantly lower height and weight standard deviation scores than HH patients . 15.4% of SLDP compared to 38.5% of HH patients had classical associated features of HH . 73.1% of patients with SLDP and 43.3% with HH had a family history of DP (p=0.007). Mean first recorded luteinizing hormone (LH) and inhibin B were lower in male patients with HH, particularly in cHH patients, but not discriminatory. There were no significant differences identified in blood concentrations of FSH, testosterone or AMH at presentation, or in bone age delay.Key clinical markers of auxology, associated signs including micropenis, and serum inhibin B may help distinguish between SLDP and HH in patients presenting with pubertal delay, and can be incorporated into clinical assessment to improve diagnostic accuracy for adolescents. However, the distinction between HH, particularly partial HH, and SLDP remains problematic. Further research into an integrated framework or scoring system would be useful in aiding clinician decision-making and optimization of treatment.   Delayed puberty (DP) is defined as the onset of puberty 2 to 2.5 standard deviations (SD) later than the general population, and is typically classified as the absence of breast development by age 13 years in girls, or testicular enlargement ≥4ml by age 14 years in boys , with a temporary picture of isolated hypogonadotrophic hypogonadism which resolves with time or a short course of sex steroid therapy , 6. SLDPOther aetiologies of DP include hypergonadotropic hypogonadism secondary to primary gonadal disorders, functional hypogonadism due to chronic illness or nutritional deficit and idiopathic hypogonadotrophic hypogonadism (HH). Whereas functional and hypergonadotropic hypogonadism may be easier to formally diagnose , 13, theThe severity of DP observed varies according to the degree of gonadotrophic deficiency , with anRegardless, all patients with HH may benefit from initiation of hormonal treatment as early as possible. Thus, whilst SLDP has often been considered a diagnosis of exclusion, typically made retrospectively once puberty is completed, it is vital to make a diagnosis of HH as promptly as possible to prevent delay in optimising treatment . Even foPrevious research into distinguishing between SLDP and HH have identified several potential differentiating markers . From a This was a retrospective study of paediatric and young adult patients with central delayed puberty who had completed puberty, identified through the NIHR clinical research network portfolio study (CPMS ID 39730) collating patients evaluated for delayed puberty within the United Kingdom from 2015 to 2023. Six paediatric endocrine centres contributed patients to the study: Royal London Children’s Hospital Barts Health NHS Trust, Great Ormond Street Hospital for Children NHS Foundation Trust, University College London Hospitals NHS Foundation Trust, Countess of Chester Hospital NHS Foundation Trust, Guy’s and St Thomas’ NHS Foundation Trust and Sheffield Teaching Hospitals NHS Foundation Trust. Ethical approval was granted by the London–Chelsea NRES committee and the UK NHS Health Research Authority (13/LO/0257), with all participants or parents of child patients providing written informed consent.Delayed puberty was defined as attaining Tanner stage G2 or B2 at 2 standard deviations later than the population average, thus a threshold of later than 14 years for boys and 13 years for girls. Arrested or stalled puberty, with spontaneous entry into puberty with attainment of G2 or B2, followed by slow or absent further progression, was assessed via Copenhagen Puberty Study nomograms  . PatientPhenotypic data were manually extracted from clinical information and investigations held electronically and in patient notes, including data pertaining to auxology, Tanner staging, testicular volume, blood biochemistry , bone age, and hormonal treatment. All data were reviewed and analysed independently by two researchers. The application Auxology  was used to complete auxology for all anthropometric characteristics including mid-parental height (MPH) and height velocity (HV). Adult height was calculated as when height velocity fell to <1cm/year. LH and FSH were measured via ICMA. Where blood test results were below the limit of detection (LOD), 50% of the LOD was used for subsequent statistical analysis . Bone agA confirmed family history of SLDP was defined as maternal age of menarche above the age of 15 years, or an immediate family member having either hormonal treatment for delayed puberty or delayed pubertal onset beyond 13 years in females and 14 years in males. A possible family history was defined as any other mention of suspected delayed puberty  in a family member.Included ‘red flag’ signs for HH were micropenis or cryptorchidism , anosmia or hyposmia, cleft lip or palate, synkinesis, renal anomalies, and limb anomalies. Data at presentation were extracted from patients’ first referrals or first consultations with tertiary endocrinology services where available. Pubertal onset data were classified as when testicular volume reached 4ml in males (G2), or Tanner stage B2 was documented in females. End of puberty data were extracted at the point where stage B4 or G4 was documented.Statistical analysis was completed using IBM SPSS version 28 and R, with mean values displayed ± standard deviation and a P value of <0.05 considered statistically significant. Z-scores (SDS) for weight and height parameters were used to standardise weight and height data for age. Graphs were created using GraphPad Prism 8.The cohort included 78 patients with delayed puberty, of whom 52 patients (66.7%) had a final diagnosis of SLDP and 26 (33.3%) were diagnosed with HH. Of the patients with HH, 17 (65.4%) had a diagnosis of partial HH (pHH) and 9 (34.6%) had complete HH (cHH). Both SLDP and HH populations were predominantly male (90.4% and 84.6% respectively), of heterogenous ethnicity with the largest minority of white Caucasian heritage . There were no significant differences in gender (p=0.45) or ethnicity (p=0.96) between the two diagnostic groups. SLDP patients were followed up for an average of 5.19 ± 2.71 years from presentation and HH patients for 5.14 ± 3.32 years (p=0.99). A summary of phenotypic characteristics can be found in A family history of delayed puberty was more common in patients with a final diagnosis of SLDP, with 73.1% of SLDP patients having a definite or possible family history of DP, as compared to 43.3% of patients with HH (p=0.001). Family history of delayed puberty was particularly rare in patients with cHH, reported in only 11.1% of this subgroup (p=0.003). The maternal age of menarche was on average one year later in the SLDP group than the HH group, with mean ages of 14.3 ± 1.8 and 13.2 ± 2.2 years respectively, but this difference did not reach significance (p=0.22). Only a small number of patients in each group had maternal age of menarche at age 15 years or above . In contrast to a family history of DP, a family history of consanguinity was rare in this cohort in both SLDP patients (5.8%) and in patients with HH (7.7%).Parental height was not different between the two diagnostic groups, with mean MPH of 174.7 ± 7.9cm in males with SLDP, and 175.7 ± 7.1cm in male patients with HH (p=0.635). Mean MPH was 162.4 ± 5.0cm in female SLDP patients, and 161.3 ± 7.4cm in female HH patients.The mean age at presentation in males with SLDP (14.9 ± 1.47 years) was younger that in those with HH (15.7 ± 2.51 years), but this did not reach significance p=0.09, Table 2.Bone age at presentation was delayed in both male diagnostic groups; whilst there was a greater degree of bone age delay in the SLDP group this did not reach significance . However, the difference in height SD for chronological age at presentation was not seen when height SD score for bone age was compared between the two groups (height SD score for bone age of 0.02 ± 1.16 in SLDP versus 0.56 ± 1.67 in HH), suggesting that much of the difference seen is due to delay in physical maturation of the SLDP group. There was no significant difference in males at presentation in height velocity SD score for chronological age (p=0.90).Female mean age at presentation was 14.0 ± 1.69 years for SLDP patients and 15.3 ± 2.61 years for HH patients. Female patients both with SLDP and HH were below average height, weight and BMI at presentation Table 2.At presentation, 16.1% of male SLDP patients and 58.8% of male HH patients were pre-pubescent with testicular volume <4ml Table 2.Half of female patients in both SLDP and HH patient groups were pre-pubertal at presentation with Tanner breast stage 1, and pubic and axillary hair staging were similar between the two diagnostic groups Table 2.As anticipated, classical ‘red flags’ for clinical detection of HH were more common in the patients with a diagnosis of HH rather than SLDP p=0.02, Table 3.Whilst mean serum LH in males at presentation was lower in cHH (0.31 ± 0.33 IU/l) than in pHH (1.40 ± 0.73 IU/l) or SLDP  and oestradiol (33.3 ± 15.0 vs 73.8 ± 55.9 pmol/l) concentrations were lower in individuals with HH than those with a final diagnosis of SLDP, but not significantly so .As expected, a far higher proportion of patients with a final diagnosis of HH received medical therapy for their delayed puberty Table 5.All male patients with SLDP that received medical therapy were treated with testosterone (n=29), mostly started intramuscularly  rather than orally  or topically . Male patients with HH were also mostly treated with testosterone alone , where intramuscular was the commonest mode of delivery (7/11) followed by topical therapy (3/11). One patient was treated only with hCG. The other male patients with HH were treated with a combination of gonadotrophins and testosterone , typically commencing testosterone and then being switched to recombinant (r)FSH and hCG (5/9). Three patients were given rFSH pre-treatment, with hCG then added in (4/9). All female patients  were treated with 17b-oestradiol either orally or transdermally.Male mean age at puberty onset was 14.9 ± 0.87 years in SLDP patients, and 15.6 ± 2.38 years in HH patients  than the HH group at puberty onset, particularly when compared to cHH (0.95 ± 1.64) rather than to pHH  patients, and remained lighter at the end of puberty (weight SD score -0.90 ± 2.01) than HH patients .The pattern of testicular development also differed between the two diagnostic groups. Patients with SLDP, both with and without sex steroid therapy, had a relatively uniform increase in testes volume, increasing from 4mls to 15-20ml over a period of 2-3yrs Figure 4At the end of puberty, serum LH remained lower in male patients with HH, most markedly in cHH patients (0.64 ± 0.49 IU/l) compared to pHH patients (2.39 IU/l ±1.58) and SLDP patients . Serum FSH was not significantly different between the two groups . Inhibin B also remained lower in males with HH (130.1 ± 85.3 pg/ml) than in the SLDP group , despite gonadotropin therapy in 38.7% of the HH patient cohort. Testosterone concentration was not different between the groups at the end of puberty, but this was confounded by the fact that at this point only 17.1% of SLDP patients remained on reproductive hormone treatment as compared to 73.3% of the HH patient group.Mean age of menarche was 17.8 ± 1.71 years in female patients with HH and 15.6 ± 0.82 in females with SLDP.Delayed pubertal onset or development is a common presentation to adolescent endocrine services, and the differentiation of SLDP from the more severe condition of congenital HH is often challenging. Whilst the expected frequency of SLDP is far higher than that of HH in children presenting with delayed onset of puberty aged 14-15 years, by the time an individual is 17-18 years old the likelihood of a diagnosis of HH is greatly increased  had caught up, perhaps due to differences in timing of hormonal treatment initiation. This height deficit in patients with SLDP remained evident throughout puberty, although notably SLDP patients had a higher height velocity at attainment of G4 suggesting that they may not yet have reached their adult height. Previous studies have reported conflicting evidence as to whether SLDP patients eventually achieve their full genetic height potential , with soPatients with HH entered puberty later than those with SLDP and achieved (treatment-induced) end of puberty status nearly a year later. Men with HH had reduced final testes volume and serum inhibin B, despite gonadotropin therapy in more than a third of this diagnostic group. It is very likely that with greater availability of gonadotropin therapy for male patients with HH, particularly the use of pre-treatment with rFSH prior to hCG therapy, testicular development can be further optimised in this treatment group .Limitations of this study include a wide variation in age and Tanner stage at participant presentation; although in this way the study reflects the real-world clinical setting. Our data included a limited sample size for particular parameters including AMH, where data on this were missing for a large number of cohort participants, as well as inter-observer variability across institutions (for example regarding Tanner staging), and limited sample sizes of female patients. Differing treatment regimes were used across the cohort, with some patients with HH receiving sex steroids and others gonadotropin therapy to achieve medication-induced puberty. Some data were also lost at the point of completion of puberty, in part due to long intervals between clinic appointments and patients discharged or lost to follow-up.In conclusion, although no definitive markers yet exist to conclusively diagnose these two conditions, this study has highlighted several phenotypic markers that may be helpful to distinguish HH from SLDP at presentation; namely lower height and weight, and higher testicular volume, serum LH and inhibin B in those with SLDP. In the case of height, weight, LH and inhibin B, these relationships persisted through puberty. To this end, it would be useful to establish these parameters as important baseline investigations across different institutions. However, in view of the high degree of overlap for many of these biochemical tests, their discriminatory power as individual biomarkers is limited, particularly for partial forms of HH. Further research is therefore warranted into optimisation of measurement intervals and cut-off values within the development of a framework or scoring system incorporating clinical, biochemical and genetic features to aid and streamline clinical decision-making in diagnostically complex cases, in order to improve diagnostic accuracy and earlier treatment optimisation.The original contributions presented in the study are included in the article/The studies involving humans were approved by the London–Chelsea NRES committee and the UK NHS Health Research Authority (13/LO/0257). The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation in this study was provided by the participants’ legal guardians/next of kin.SH conceptualised and designed the study. YA, VK, KY, KB, GB, MD, PD, CH, MM, MK, GP, SS, PS, HS, RW and SH collected the clinical data. YA, VK and SH analysed the data. YA, VK and SH wrote the original draft. LD, MD, MK critically reviewed the manuscript. YA and SH edited the final version. All authors had final responsibility for the decision to submit for publication.


A significant correlation of NFATC1 expression with Ao found . In BAV patients with PWTd > 8 mm and Ao > 21 mm the NFATC1 expression was significantly higher compared to those with PWTd ≤ 8 mm and Ao ≤ 21 mm (NFATC1 median (min–max); 45.49 (5.01–101.52) e.u. vs. 15.53 (2.36–44.40) e.u., p < 0.05 and 81.11 (20.27–101.10) e.u. mm vs. 12.16 (2.40–45.49) e.u., p < 0.05, respectively). Conclusion: In children with BAV the high expression of the NFATC1 calcineurin signaling pathway gene is associated with elevated PWTd and Ao. Background: The role of NFATC gene expression in bicuspid aortic valve (BAV) progression is not fully understood. The aim of this study is to determine the significance of NFATC1 and NFATC4 gene expression for myocardial changes in children with BAV. Methods: In 47 children with BAV, the standard Doppler echocardiographic characteristics were detected, and the expression of the NFATC1 and NFATC4 genes was studied. Results: Posterior wall thickness in diastole (PWTd) and aortic valve peak pressure gradient (AoPPG) in BAV patients were significantly higher compared to healthy controls (PWTd median (min–max), 9 (7–10) mm vs. 7 (6–8) mm; and AoPPG median (min–max), 7.79 (2.98–15.09) mm Hg vs. 2.94 (2.42–3.72) mm Hg). The expression of the NFATC1 gene in BAV children was significantly higher compared to NFATC4 (NFATC1 median (min–max); 70.88 (8.79–106.51) e.u. vs. 7.72 (1.74–22.67) e.u., respectively  Bicuspid aortic valve (BAV) is the most common congenital heart disease with a prevalence ranging from 0.5% to 1.4% in the population and is associated with severe complications, including aortopathy, and may present as asymptomatic in childhood . On the Phenotypes of BAV also demonstrated the heterogeneity in relation to subsequent aortic complications with the prevalence of BAV-RL and BAV with raphe corresponding to the development of aortic regurgitation and BAV-RN corresponding to aortic stenosis but these studies mostly included adolescents and adults ,15. ThesIn line with the above studies and the importance of calcineurin signaling pathway genes in both valve development and myocardial remodeling, these factors could also be implicated in myocardial changes in children with BAV. In this connection, detecting the significance of NFATC1 and NFATC4 expression in early myocardial remodeling in BAV children seems relevant. The aim of this study is to determine the association of NFATC1 and NFATC4 gene expression with myocardial remodeling and changes in intracardiac hemodynamics in children with BAV. This study was conducted at the Zaporizhzhya Regional Clinical Children’s Hospital. 112 patients, in whom the diagnosis of BAV was established by general clinical investigation and standard Doppler echocardiography, participated in this study. The control group included 20 healthy children neither pathology of the cardiovascular system nor heart anomalies by their clinical exam and heart ultrasound. The criteria for inclusion in the main study group were the age of patients (from 9 to 15), the diagnosis of BAV, the absence of complaints at presentation, neither ultrasound nor clinical signs of aortopathies or heart complications, and informed consent of children or their parents to conduct this study. The exclusion criteria were the age of children younger than 9 and older than 15 years old, participation in any sports, the presence of clinical signs of heart failure, congenital malformations of other organs and systems, established chromosomal abnormalities, and chronic diseases in the stage of decompensation or acute infectious diseases. After inclusion and exclusion criteria were applied, there were 47 patients with BAV in the main group without significant differences in age, BMI or gender distribution to control .Doppler echocardiography was performed using the “Xario 100” scanner  with a 2.5 MHz sensor and detection of standard parameters. The systolic function and ejection fraction of the LV were assessed by M-mode echocardiography. The parameters of the hemodynamics at the valves were assessed by Doppler measurements. Relative left ventricular posterior wall thickness (RPWT) was detected by A. Ganau . Left veThe expression level of NFATC1 and NFATC4 genes in the blood cells of patients was detected by total RNA extraction, and the obtaining of cDNA was achieved by reverse transcription using a CFX96™ Real-Time PCR Detection Systems amplifier  and a Maxima SYBR Green/ROX qPCR Master Mix (2X) reagent kit . Statistical analysis of PCR data was performed using CFX Manager ™ v3.0 software . The obtained values were presented in units of relative normalized expression compared to the expression in the control group and were taken as the 1 unit of expression (e.u.). In 47 children with BAV, the expression of the NFATC1 and NFATC4 genes was detected at the basal level and in 3 subgroups divided according to the posterior wall thickness in diastole of more than 8 mm, the aortic root diameter of more than 21 mm and the peak pressure gradient at the aortic valve of more than 6 mm Hg.t-test was scored for the presence of the difference between groups, and in the non-normal distribution the Mann–Whitney nonparametric criterion for small samples was scored. The relationship between parameters was assessed by Spearman correlations and presented in the form of a correlation matrix. In order to evaluate the multiple correlations between Doppler echocardiographic parameters and the expression of the studied NFATC genes, the correlation matrix was transformed into a gradient color pattern, with the color changing from white to deep blue for high positive R coefficients and from white to deep red for high negative R values, with numbers ranging from +1.0 to −1.0, respectively. Significant correlation coefficients were marked on the gradient pattern. Statistical analysis was performed using the Statiatica 13.0 program. The normality of distribution was assessed using the Shapiro–Wilk test. The data were presented in the form M ± m, where M is the sample mean, and m is the error of mean in the case of a normal distribution and in the form of median (min–max) in the case when the distribution deviated from normal. In assessing the significance between groups with normal distribution, the Student’s All procedures performed in studies involving human participants were in accordance with the ethical standards according to the principles of the Declaration of Helsinki, and this study was approved by Zaporizhzhya State Medical University Clinical Research Ethical Committee (Protocol Number 5 from 17 April 2019). In children with BAV, significant differences in Doppler echocardiographic parameters were observed between groups . p < 0.05), which clearly reflected the morphological and functional characteristics of this defect. At the same time, there were no significant differences in other Doppler echocardiographic data between the groups. Notably, RPWT and LVMMI were significantly higher in 29 (61.7%) of the children with BAV with PWTd > 8 mm compared to those with PWTd < 8 mm (p < 0.05), which was also associated with a significantly increased Ao, as shown in These included increased Ao, SWTd and PWTd, AoPPG, LVDD, LVM, LVMMI, RPWT and the acceleration of the AVV (p < 0.05), although the expression of both genes was 71-fold and 8-fold higher compared to control, respectively.The evaluation of NFATC1 and NFATC4 gene expression in children with BAV has revealed a significantly higher expression of the NFATC1 gene (NFATC1 median (min-max) 70.88 (8.79–106.51) e.u. vs. 7.72 (1.74–22.67) e.u., respectively p < 0.05), and NFATC4 with MVV and PVPPG was shown . Other significant correlations reflected interactions in functional Doppler echocardiographic parameters of BAV children ; stroke volume with LVDD and LVSD ; ejection fraction with LVSD and LVSV ; MLAPD to LALD ). The expression levels of the NFATC1 and NFATC4 genes in the change of defect-associated parameters of Doppler echocardiography in children with BAV  with respect to the insignificant differences in NFATC4 caused by this parameter (NFATC4 median (min–max); 12.60 (7.72–37.41) e.u. vs. 6.31(1.74–45.09) e.u., p > 0.05). For both NFATC1 and NFATC4 expression in AoPPG of more than 6 mm Hg compared to value less than or equal to 6 mm Hg, there was no significance detected (NFATC1 median (min-max), 96.25 (15.50–106.50) e.u. vs. 27.53 (2.36–91.54) e.u.), p > 0.05; and NFATC4 median (min-max), 6.24 (1.74–45.09) e.u. vs. 10.16 (3.08–17.96) e.u., p > 0.05). The parameter of Ao related to the value of 21 mm was found to be significantly increased for NFATC1 expression (NFATC1 median (min–max); 81.11 (20.27–101.10) e.u. at Ao >= 21 mm vs. 12.16 (2.40–45.49) e.u. at Ao < 21 mm p < 0.05) and was not significant for NFATC4 expression (NFATC4 median (min-max); 10.16 (1.45–45.09) e.u. at Ao >= 21 vs. 6.38 (1.74–22.67) e.u. at Ao < 21 mm p > 0.05).In children with an increased PWTd of more than 8 mm compared to BAV children with PWTd of less than or equal to 8 mm, the level of NFATC1 expression was significantly higher (NFATC1 median (min–max); 45.49 (5.01–101.52) e.u. vs. 15.53 (2.36–44.40) e.u., The genes of the NFATC family as transcription factors play an essential role in many pathological processes, such as myocardial hypertrophy tumorigenesis and immune response. The study of the expression of these genes in children with BAV has both diagnostic and prognostic value because of involvement in valvulogenesis and the presence of polymorphisms that could influence the development of this anomaly. Our previous investigation showed the predominance of the rs11665469 homozygous TT genotype of NFATC1 in children with BAV , and in The established association of NFATC1 gene expression levels with LV and aortic changes in children with BAV allow us to define a risk stratification strategy regarding complications and future cardiovascular events in these patients who are experiencing increasing aortic diameter. High NFATC1 expression in association with changes in PWTd and Ao in children with BAV is indicative of intense and progressive myocardial changes and requires closer follow-ups with clinical evaluation and Doppler echocardiography.This study has some limitations due to overlap in the parameters studied. Some patients appeared to have both elevated PWTd and Ao, or Ao with elevated AoPPG. Another limitation concerns some phenotypic heterogenicity in BAV anatomy that could affect AV hemodynamics and was not included in this study, However, the association of LV and aortic changes with the level of NFATC1 expression, but not with AV hemodynamics, was found to reflect a predominant remodeling caused by a possible increased expression of mutant genes of the transcriptional cascade associated with BAV. In addition, the results obtained from the expression of NFATC1 in children with BAV could be the basis for a therapeutic approach based on expressive activity regulation.The calcineurin signaling pathway gene NFATC1, but not NFATC4, is highly expressed in children with BAV. This increased expression of NFATC1 in children with BAV is associated with myocardial changes in elevated PWTd and also increased Ao. The expression of this gene could indicate possible cardiovascular complications in these patients.


Measurement of multimorbidity in research is variable, including the choice of the data source used to ascertain conditions. We compared the estimated prevalence of multimorbidity and associations with mortality using different data sources.A cross-sectional study of SAIL Databank data including 2,340,027 individuals of all ages living in Wales on 01 January 2019. Comparison of prevalence of multimorbidity and constituent 47 conditions using data from primary care (PC), hospital inpatient (HI), and linked PC-HI data sources and examination of associations between condition count and 12-month mortality.Using linked PC-HI compared with only HI data, multimorbidity was more prevalent (32.2% versus 16.5%), and the population of people identified as having multimorbidity was younger (mean age 62.5 versus 66.8 years) and included more women (54.2% versus 52.6%). Individuals with multimorbidity in both PC and HI data had stronger associations with mortality than those with multimorbidity only in HI data (adjusted odds ratio 8.34 [95% CI 8.02-8.68] versus 6.95 (95%CI 6.79-7.12] in people with ≥ 4 conditions). The prevalence of conditions identified using only PC versus only HI data was significantly higher for 37/47 and significantly lower for 10/47: the highest PC/HI ratio was for depression (14.2 [95% CI 14.1–14.4]) and the lowest for aneurysm (0.51 [95% CI 0.5–0.5]). Agreement in ascertainment of conditions between the two data sources varied considerably, being slight for five (kappa < 0.20), fair for 12 (kappa 0.21–0.40), moderate for 16 (kappa 0.41–0.60), and substantial for 12 (kappa 0.61–0.80) conditions, and by body system was lowest for mental and behavioural disorders. The percentage agreement, individuals with a condition identified in both PC and HI data, was lowest in anxiety (4.6%) and highest in coronary artery disease (62.9%).The use of single data sources may underestimate prevalence when measuring multimorbidity and many important conditions . Caution should be used when interpreting findings of research examining individual and multiple long-term conditions using single data sources. Where available, researchers using electronic health data should link primary care and hospital inpatient data to generate more robust evidence to support evidence-based healthcare planning decisions for people with multimorbidity.The online version contains supplementary material available at 10.1186/s12916-023-02970-z. Multimorbidity, most commonly defined as the coexistence of two or more long-term conditions, is an issue of global importance because of its association with increased healthcare use, mortality, and reduced quality of life . AccuratMeasurement of multimorbidity in research is highly variable in terms of the definition of multimorbidity used  , 4, the Electronic health data are increasingly available for research, with 50% of upper-middle and high-income countries globally adopting these in primary and/or secondary care settings , 8. DespThis cross-sectional study used routinely collected anonymised data available in the SAIL Databank and consisted of individuals of all ages living in Wales and registered with a GP contributing data to the Secure Anonymised Information Linkage (SAIL) Databank on 1 January 2019. Intentionally, this study examines condition coding outside the COVID-19 pandemic to avoid capturing the effects of related restrictions and associated decreases in the diagnosis of physical and mental health conditions . The stuPC data obtained from the Welsh Longitudinal General Practice Dataset (WLGP) were used to define conditions using Read version 2 codes , prescribing and/or laboratory data . HI dataChoice of the 47 conditions was based on results of a recent Delphi consensus study recommending those to include in the measurement of multimorbidity . To ensure that the study reflected a fair comparison between ascertainment using codes present in PC and HI datasets based on availability within each data source, prescribing data were applied to only PC and to linked PC-HI data. Conditions were categorised by the International Classification of Diseases and Related Health Problems 10th Revision (ICD-10)  and  versus 10.8% [95% CI 10.7 to 10.9]) and mental and behavioural disorders (median 87.4% [IQR 86.5 to 95.4] versus 31.4% [IQR 17.2 to 42.2]) respectively. In contrast, conditions in diseases of the circulatory system (79.2% [IQR 68.8 to 88.1] versus 67.0% [IQR 54.2 to 80.4]) and neoplasms (78.6% [95% CI 78.2 to 78.9] versus 75.6% [95% CI 75.2 to 75.9]) had the smallest difference. Compared with linked HI-PC data, only PC data ascertained a larger proportion than only HI on averaging across all conditions: median ascertainment using only PC data was 84.7% (IQR 76.7 to 90.4) versus 50.1% (IQR 31.4 to 67.0) for only HI data  and depression 5.1%) to a maximal agreement in coronary artery disease and (62.9%) and multiple sclerosis (60.4%). ICD-10 chapters with the highest percent agreement were endocrine, nutritional, and metabolic diseases (median 44.9% [IQR 42.6 to 48.4]) and diseases of the nervous system (median across conditions in that chapter 38.10% [IQR 25.3 to 49.7]). Percent agreement was lowest for diseases of the ear and mastoid process (median 6.9% [IQR 6.6 to 7.3]) and mental and behavioural disorders (median 22.7% [IQR 5.1 to 28.7])  than only HI (16.5%) data and higher still using linked PC-HI (32.2%) data. The population of people identified as having multimorbidity using linked PC-HI data compared to only HI was younger, included a higher proportion of women, and people identified as multimorbid in both PC and HI had a stronger association with mortality. Using only PC data identified more people as having most of the 47 conditions than using only HI, and this was most marked for mental and behavioural and sensory disorders. Concordance between data sources was variable across conditions and ICD-10 body systems. The use of single data sources may underestimate the prevalence of multimorbidity and most individual conditions, especially mental and behavioural disorders. Findings from this study support the use of linked primary care and hospital inpatient data where available.Strengths of the study are the inclusion of almost the entire adult population of Wales and examination of multimorbidity and a large number of individual conditions recommended for use in multimorbidity research , providiConsistent with our findings, a study from Canada found varying degrees of discordance comparing ascertainment of seven conditions  between the Canadian Community Health Survey (patient self-report) and health administrative data . AscertaIt is important to note the variation in prevalence estimates for individual conditions and multimorbidity where differing rules for ascertainment have been applied across studies. Ascertainment of conditions using the same criteria can be similar; for example, estimates of hypertension prevalence calculated as any time look-back for clinical codes were 19.52% in this study compared with 18.2% in a recent study using linked primary care to HES in CPRD   who repoSimilar to the 14-fold higher ascertainment of depression using only PC versus only HI data in this study, previous studies have shown that the recording of depression in hospital data is incomplete and has been attributed to clinicians considering depression as being non-relevant to admissions for physical conditions . A similThe implication of the study for clinicians and managers is that coding of conditions in the two settings seems inconsistent, reflecting often a manual transfer of diagnoses between settings. More consistent coding is important to improve information transfer across the primary care-hospital boundary, which is a critical underpinning for good care. It will be necessary to examine the effects of the implementation of SNOMED-CT codes in electronic health records in the UK. Due to the use of a more consistent medical vocabulary, it is anticipated that the introduction of SNOMED-CT will improve precision in the exchange of clinical information between primary and secondary care settings for both clinical and research purposes and therefore comparability with international studies where the same system is used . For resThis study highlights the importance of, where available, linking primary care and hospital inpatient data when measuring multimorbidity to avoid underestimation of prevalence and underrepresentation of certain population groups. Robust and consistent methods across studies are needed to improve comparability and reproducibility and ultimately improve the quality of research and the clinical trials and guideline development needed to support people with multimorbidity.Additional file 1: Choice of long-term conditions in relation to those included by “Measuring multimorbidity in research: a Delphi consensus study” .Additional file 2: List of included long-term conditions including explanation of rules and code lists used to define Conditions.Additional file 3: Associations between long-term conditions and mortality by data source.Additional file 4: Measures of concordance of long-term conditions using primary care and hospital inpatient data.Additional file 5: Measures of concordance of long-term conditions using different data sources.