METHODS: To estimate fertility indicators from 1950 to 2021, mixed-effects regression models and spatiotemporal Gaussian process regression were used to synthesise data from 8709 country-years of vital and sample registrations, 1455 surveys and censuses, and 150 other sources, and to generate age-specific fertility rates (ASFRs) for 5-year age groups from age 10 years to 54 years. ASFRs were summed across age groups to produce estimates of total fertility rate (TFR). Livebirths were calculated by multiplying ASFR and age-specific female population, then summing across ages 10-54 years. To forecast future fertility up to 2100, our Institute for Health Metrics and Evaluation (IHME) forecasting model was based on projections of completed cohort fertility at age 50 years (CCF50; the average number of children born over time to females from a specified birth cohort), which yields more stable and accurate measures of fertility than directly modelling TFR. CCF50 was modelled using an ensemble approach in which three sub-models (with two, three, and four covariates variously consisting of female educational attainment, contraceptive met need, population density in habitable areas, and under-5 mortality) were given equal weights, and analyses were conducted utilising the MR-BRT (meta-regression-Bayesian, regularised, trimmed) tool. To capture time-series trends in CCF50 not explained by these covariates, we used a first-order autoregressive model on the residual term. CCF50 as a proportion of each 5-year ASFR was predicted using a linear mixed-effects model with fixed-effects covariates (female educational attainment and contraceptive met need) and random intercepts for geographical regions. Projected TFRs were then computed for each calendar year as the sum of single-year ASFRs across age groups. The reference forecast is our estimate of the most likely fertility future given the model, past fertility, forecasts of covariates, and historical relationships between covariates and fertility. We additionally produced forecasts for multiple alternative scenarios in each location: the UN Sustainable Development Goal (SDG) for education is achieved by 2030; the contraceptive met need SDG is achieved by 2030; pro-natal policies are enacted to create supportive environments for those who give birth; and the previous three scenarios combined. Uncertainty from past data inputs and model estimation was propagated throughout analyses by taking 1000 draws for past and present fertility estimates and 500 draws for future forecasts from the estimated distribution for each metric, with 95% uncertainty intervals (UIs) given as the 2·5 and 97·5 percentiles of the draws. To evaluate the forecasting performance of our model and others, we computed skill values-a metric assessing gain in forecasting accuracy-by comparing predicted versus observed ASFRs from the past 15 years (2007-21). A positive skill metric indicates that the model being evaluated performs better than the baseline model (here, a simplified model holding 2007 values constant in the future), and a negative metric indicates that the evaluated model performs worse than baseline.

FINDINGS: During the period from 1950 to 2021, global TFR more than halved, from 4·84 (95% UI 4·63-5·06) to 2·23 (2·09-2·38). Global annual livebirths peaked in 2016 at 142 million (95% UI 137-147), declining to 129 million (121-138) in 2021. Fertility rates declined in all countries and territories since 1950, with TFR remaining above 2·1-canonically considered replacement-level fertility-in 94 (46·1%) countries and territories in 2021. This included 44 of 46 countries in sub-Saharan Africa, which was the super-region with the largest share of livebirths in 2021 (29·2% [28·7-29·6]). 47 countries and territories in which lowest estimated fertility between 1950 and 2021 was below replacement experienced one or more subsequent years with higher fertility; only three of these locations rebounded above replacement levels. Future fertility rates were projected to continue to decline worldwide, reaching a global TFR of 1·83 (1·59-2·08) in 2050 and 1·59 (1·25-1·96) in 2100 under the reference scenario. The number of countries and territories with fertility rates remaining above replacement was forecast to be 49 (24·0%) in 2050 and only six (2·9%) in 2100, with three of these six countries included in the 2021 World Bank-defined low-income group, all located in the GBD super-region of sub-Saharan Africa. The proportion of livebirths occurring in sub-Saharan Africa was forecast to increase to more than half of the world's livebirths in 2100, to 41·3% (39·6-43·1) in 2050 and 54·3% (47·1-59·5) in 2100. The share of livebirths was projected to decline between 2021 and 2100 in most of the six other super-regions-decreasing, for example, in south Asia from 24·8% (23·7-25·8) in 2021 to 16·7% (14·3-19·1) in 2050 and 7·1% (4·4-10·1) in 2100-but was forecast to increase modestly in the north Africa and Middle East and high-income super-regions. Forecast estimates for the alternative combined scenario suggest that meeting SDG targets for education and contraceptive met need, as well as implementing pro-natal policies, would result in global TFRs of 1·65 (1·40-1·92) in 2050 and 1·62 (1·35-1·95) in 2100. The forecasting skill metric values for the IHME model were positive across all age groups, indicating that the model is better than the constant prediction.

INTERPRETATION: Fertility is declining globally, with rates in more than half of all countries and territories in 2021 below replacement level. Trends since 2000 show considerable heterogeneity in the steepness of declines, and only a small number of countries experienced even a slight fertility rebound after their lowest observed rate, with none reaching replacement level. Additionally, the distribution of livebirths across the globe is shifting, with a greater proportion occurring in the lowest-income countries. Future fertility rates will continue to decline worldwide and will remain low even under successful implementation of pro-natal policies. These changes will have far-reaching economic and societal consequences due to ageing populations and declining workforces in higher-income countries, combined with an increasing share of livebirths among the already poorest regions of the world.

AIMS: This study aimed to explore the prevalence, demographic factors, and motivations behind drug mixing with tobacco in shisha among university students in Jordan.

METHODS: In this descriptive cross-sectional study, a structured questionnaire was used to collect data on participants' demographics, shisha smoking habits, drug mixing practice and the motivations behind it. Four hundred and sixty-nine (469) students, aged 18-30 years, including medical and non-medical students, from two universities in Jordan participated in this study.

RESULTS: Approximately 18% of participants reported mixing drugs with tobacco in shisha, with paracetamol being the predominant choice (80%). Motivations varied, with 42% seeking euphoric effects, 46% a relaxing experience, and 12% a sedative outcome. Males (73%) showed a higher frequency of drug mixing compared to females (27%). In addition, non-medical reported mixing drugs with the tobacco of water-pipe more than medical students.

METHODS: This prospective, multicentre, open-label, randomised, phase 3a trial (explorer8) was conducted at 69 investigational sites in 31 countries. Eligible patients were male, aged 12 years or older, and had congenital severe haemophilia A or moderate or severe haemophilia B without inhibitors and with documented treatment with clotting factor concentrate in the 24 weeks before screening. The trial was paused because of non-fatal thromboembolic events in three patients (two from this trial [explorer8] and one from a related trial in haemophilia with inhibitors [explorer7; NCT04083781]) and restarted with mitigation measures, including a revised dosing regimen of subcutaneous concizumab at 1·0 mg/kg loading dose on day 1 and subsequent daily doses of 0·20 mg/kg from day 2, with options to decrease to 0·15 mg/kg, stay on 0·20 mg/kg, or increase to 0·25 mg/kg on the basis of concizumab plasma concentration measured after 4 weeks on concizumab. Patients recruited after treatment restart were randomly assigned 1:2 using an interactive web response system to receive no prophylaxis and continue on-demand clotting factor (group 1) or concizumab prophylaxis (group 2). The primary endpoints were the number of treated spontaneous and traumatic bleeding episodes for patients with haemophilia A and haemophilia B separately, assessed at the confirmatory analysis cutoff in randomly assigned patients. Analyses were by intention-to-treat. There were two additional groups containing non-randomly-assigned patients: group 3 contained patients who entered the trial before the trial pause and were receiving concizumab in the phase 2 trial (explorer5; NCT03196297), and group 4 contained patients who received previous clotting factor concentrate prophylaxis or on-demand treatment in the non-interventional trial (explorer6; NCT03741881), patients randomly assigned to groups 1 or 2 before the treatment pause, and patients from explorer5 enrolled after the treatment pause. The safety analysis set contained all patients who received concizumab. Superiority of concizumab over no prophylaxis was established if the two-sided 95% CI of the treatment ratio was less than 1 for haemophilia A and for haemophilia B. This trial is registered with ClinicalTrials.gov, NCT04082429, and its extension part is ongoing.

FINDINGS: Patients were recruited between Nov 13, 2019 and Nov 30, 2021; the cutoff date for the analyses presented was July 12, 2022. 173 patients were screened, of whom 148 (86%) were randomly assigned or allocated to the four groups in the study after trial restart on Sept 30, 2020 (nine with haemophilia A and 12 with haemophilia B in group 1; 18 with haemophilia A and 24 with haemophilia B in group 2; nine with haemophilia A in group 3; and 46 with haemophilia A and 30 with haemophilia B in group 4). The estimated mean annualised bleeding rate ratio for treated spontaneous and traumatic bleeding episodes during concizumab prophylaxis versus no prophylaxis was 0·14 (95% CI 0·07-0·29; p<0·0001) for patients with haemophilia A and 0·21 (0·10-0·45; p<0·0001) for patients with haemophilia B. The most frequent adverse events in patients who received concizumab were SARS-CoV-2 infection (19 [13%] of 151 patients), an increase in fibrin D-dimers (12 [8%] patients), and upper respiratory tract infection (ten [7%] patients). There was one fatal adverse event possibly related to treatment (intra-abdominal haemorrhage in a patient from group 4 with haemophilia A with a long-standing history of hypertension). No thromboembolic events were reported between the trial restart and confirmatory analysis cutoff.

INTERPRETATION: Concizumab was effective in reducing the bleeding rate compared with no prophylaxis and was considered safe in patients with haemophilia A or B without inhibitors. The results of this trial suggest that concizumab has the potential to be one of the first subcutaneous treatment options for patients with haemophilia B without inhibitors.

Methods: Sixty-four patients aged 18-60 years, American Society of Anaesthesiologists (ASA) class I-II who underwent elective surgery were randomised to a Marsh group (n= 32) or Schnider group (n= 32). All the patients received a 1 μg/kg loading dose of dexmedetomidine, followed by TCI anaesthesia with remifentanil at 2 ng/mL. After the effect-site concentration (Ce) of remifentanil reached 2 ng/mL, propofol TCI induction was started. Anaesthesia induction commenced in the Marsh group at a target plasma concentration (Cpt) of 2 μg/mL, whereas it started in the Schnider group at a target effect-site concentration (Cet) of 2 μg/mL. If induction was delayed after 3 min, the target concentration (Ct) was gradually increased to 0.5 μg/mL every 30 sec until successful induction. The Ct at successful induction, induction time, Ce at successful induction and haemodynamic parameters were recorded.

Results: The Ct for successful induction in the Schnider group was significantly lower than in the Marsh group (3.48 [0.90] versus 4.02 [0.67] μg/mL;P= 0.01). The induction time was also shorter in the Schnider group as compared with the Marsh group (134.96 [50.91] versus 161.59 [39.64]) sec;P= 0.02). There were no significant differences in haemodynamic parameters and Ce at successful induction.

Methods: This cross-sectional study was conducted with school-going children from 16 selected schools of a tribal district in Jharkhand using multistage cluster random sampling. In each selected school, 60 students, 30 boys and 30 girls, were chosen randomly, totaling 960 children (full data was for 935 children only). Growth charts were created using Lambda-Mu-Sigma (LMS) chart maker version 2.5 for height, weight and body mass index (BMI). In the charts, the LMS values with Z scores for each age and respective height and weight for boys and girls were recorded.

Results: The 468 boys and 467 girls were in the range of 6-14 years of age. Percentile values obtained for the measured heights in centimetres were evaluated and compared with Indian Academy of Pediatrics reference charts for boys and girls for the same age group, and our values were found to be on the lower side. We were able to plot a growth chart of the data set; as the tribal children's ethnicity is different, this growth chart might be used to assess nutritional status.

Methods: A cross-sectional survey was conducted among 176 adolescents aged between 13 and 19 years of age with the majority being Malay and Muslim. The Brief Reasons for Living for Adolescents (BRFL-A), Jalowiec Coping Scale and Suicide Ideation Scale were employed.

Results: The results showed that the reasons for living and palliative coping strategy correlated negatively with suicide ideation; although, further analysis using multiple regression revealed that family alliance and optimistic and palliative coping strategies were found to be significant reasons for living that protect adolescents from suicidal thoughts. Also, those adolescents who used emotive and evasive coping strategies had higher suicidal ideation.

Methods: We included patients with histopathologically diagnosed head and neck cancers who had received radiation, with an Eastern Cooperative Oncology Group (ECOG) performance status 0-1 and age range of 15-60 years. Patients with prior radiotherapy and chemotherapy, edentulous status, total parotidectomy, sicca syndrome or on xerosis-induced medications were excluded. We assigned 15 patients each to the Oral7® and salt-soda groups.

Results: There was no significant difference in the mean Decayed, Missing and Filling Teeth (DMFT) score between groups. Head and neck cancer patients who were on Oral7® had a significantly better quality of life than those on salt-soda in relation to the swallowing problems, social eating, mouth opening, xerostomia and illness scales. Patients who were on Oral7® had a significantly lower xerostomia score than patients on salt-soda mouthwash. Patients on Oral7® had a significantly lower mucositis score in week 5-7 compared to patients in the salt-soda group.

Methods: This school-based, non-randomised controlled study was conducted among secondary school students with a total of 236 respondents. The KAPS score were assessed before and 1 month after using self-administered validated KAPS questionnaire on TB. Analysis was done using repeated measures ANOVA.

Results: The mean percentage score (SD) for baseline knowledge, attitude, practice and stigma score for the respondents were 54.0 (4.48), 65.6 (1.74), 70.0 (1.43) and 66.0 (6.88), respectively. There was a significant difference (P < 0.001) in the knowledge and stigma score for intervention group compared to control group, adjusted for gender, ethnicity and smoking status 4 weeks post-TB educational programme. However, with regards to attitude and practice score, there was no significant difference (P = 0.210 and P = 0.243, respectively).

METHODS: This cross-sectional study examined demographic, clinical and biochemical data of all newly diagnosed Malaysian children aged 0-18 years with T1DM over 11 years from a single centre. Regression analyses were used to determine predictors and trends.

RESULTS: The overall DKA rate was 73.2%, 54.9% of the DKA cases were severe. Age ≥5 years [odds ratio (OR): 12.29, 95% confidence interval (CI): 1.58, 95.58, p=0.017] and misdiagnosis (OR: 3.73, 95% CI: 1.36, 10.24 p=0.01) were significant predictors of a DKA presentation. No significant trends in the annual rates of DKA, severe DKA nor children <5 years presenting with DKA were found during study period.

DESIGN: Prospective, single-blind, randomised controlled trial with an allocation ratio of 1:1 over a 12-week follow-up.

SETTING: Government Orthodontic Unit, Raub Dental Clinic, Raub, Pahang, Ministry of Health, Malaysia.

PARTICIPANTS: A total of 40 patients aged 13-25 years undergoing orthodontic treatment with fixed appliances.

METHODS: The 40 patients were recruited and randomly allocated to a control (n = 20) or trial group (n = 20). Participants in the trial group received weekly oral hygiene reminders via the WhatsApp application for 12 weeks, while the control group did not receive any reminders. The primary outcome was oral hygiene, which was measured by the single-blinded examiner using the Orthodontic Plaque Index (OPI) at three orthodontic check-ups: baseline (T0); 6-week follow-up (T1); and 12-week follow-up (T2).

RESULTS: The mean age of participants was 17 years, and 80% were female. At the end of the 12-week follow-up, improvements in OPI scores were observed, regardless of the intervention. At T2, the median OPI score for the trial group (n = 20) was 0 (interquartile range [IQR = 0) while that for the control group (n = 20) was 2 (IQR = 0). A Mann-Whitney U test revealed a statistically significant difference (P <0.05), with effect size r = 0.87 between the control and trial groups, whereby the latter witnessed marked improvement in OPI throughout the visits. No harms or adverse effects occurred in this trial.

METHODOLOGY: We recruited 175 subjects, aged 7 to 18 years old, referred for obesity. We studied their demography (age, gender, ethnicity, family background), performed clinical/auxological examinations [weight, height, body mass index (BMI), waist circumference (WC), blood pressure (BP)], and analyzed their biochemical risks associated with metabolic syndrome [fasting plasma glucose (FPG), fasting lipid profile (FLP), fasting insulin, liver function tests (LFT)]. MetS was identified according to the criteria proposed by the International Diabetes Federation (IDF) for pediatric obesity. Multiple logistic regression models were used to examine the associations between risk variables and MetS.

RESULTS: The prevalence of metabolic syndrome among children with obesity was 56% (95% CI: 48.6 to 63.4%), with a mean age of 11.3 ± 2.73 years. Multiple logistic regression analysis showed age [adjusted odds ratio (OR) 1.27, 95% CI: 1.15 to 1.45] and sedentary lifestyle (adjusted OR 3.57, 95% CI: 1.48 to 8.59) were the significant factors associated with metabolic syndrome among obese children.