There has been much discussion and debate around the underreporting of COVID-19 infections and deaths in India. In this short report we first estimate the underreporting factor for infections from publicly available data released by the Indian Council of Medical Research on reported number of cases and national seroprevalence surveys. We then use a compartmental epidemiologic model to estimate the undetected number of infections and deaths, yielding estimates of the corresponding underreporting factors. We compare the serosurvey based ad hoc estimate of the infection fatality rate (IFR) with the model-based estimate. Since the first and second waves in India are intrinsically different in nature, we carry out this exercise in two periods: the first wave  and part of the second wave . The latest national seroprevalence estimate is from January 2021, and thus only relevant to our wave 1 calculations.Both wave 1 and wave 2 estimates qualitatively show that there is a large degree of “covert infections” in India, with model-based estimated underreporting factor for infections as 11.11  10.71–11.47) and for deaths as 3.56 (95% CrI 3.48–3.64) for wave 1. For wave 2, underreporting factor for infections escalate to 26.77 (95% CrI 24.26–28.81) and to 5.77 (95% CrI 5.34–6.15) for deaths. If we rely on only reported deaths, the IFR estimate is 0.13% for wave 1 and 0.03% for part of wave 2. Taking underreporting of deaths into account, the IFR estimate is 0.46% for wave 1 and 0.18% for wave 2 (till May 15). Combining waves 1 and 2, as of May 15, while India reported a total of nearly 25 million cases and 270 thousand deaths, the estimated number of infections and deaths stand at 491 million (36% of the population) and 1.21 million respectively, yielding an estimated (combined) infection fatality rate of 0.25%. There is considerable variation in these estimates across Indian states. Up to date seroprevalence studies and mortality data are needed to validate these model-based estimates.The online version contains supplementary material available at 10.1186/s13104-021-05652-2. In late August 2020, India was predicted to surpass the United States in terms of reported case counts from SARS-CoV-2 infections. To the surprise of many modelers the curve turned corner in late September with the highest number  of daily new cases reported on 16 September 2020 [We review available seroprevalence results that vary across states and specifically across rural versus urban areas. Whereas in many major metros and slum areas the seroprevalences were reported to be more than 50%, in rural areas there is a wide variation Table . The latSupplementary Methods) with a compartment for unascertained cases and deaths after accounting for the false negative rates of RT-PCR and rapid antigen tests used in India [Using a compartmental epidemiologic model (as explained in the in India  we estimmentclass2pt{minimeff) crossed unity for the first time in 2021 on February 14 and we allow a two-week incubation period before that date. Using daily time series of case, death and recovery counts we compare fatality rates and underreporting factors associated with the two time periods using the compartmental models. Further, using observed data from the two waves and the model-based underreporting factor estimates, we compute cumulative case and death counts for the total duration of waves 1 and 2. We multiply the wave-specific cumulative counts with relevant underreporting factors and sum over both waves to get combined counts of cases and deaths. The estimated numbers of cumulative deaths and infections provide us with a combined IFR estimate for India as of May 15.Due to the stress on the healthcare and reporting infrastructure, the fatality and underreporting processes were very different across the two waves. Thus, we consider two separate phases of the pandemic, with wave 1 from April 1, 2020–January 31, 2021 and wave 2 starting on February 1, 2021. This definition is artificial and is guided by the fact that the national effective reproduction number  in India is low. With 154,428 deaths and 10.76 million cases reported as of January 31, 2021 the estimated CFR for wave 1 is 1.435%  [1  is 0.129% (95% CrI 0.125–0.134%) and IFR2  is 0.461% (95% CrI 0.455–0.468%) with an underreporting factor for cases estimated at 11.11 (95% CrI 10.71–11.47) and for deaths at 3.56 (95% CrI 3.48–3.64). These model-based estimates in wave 1 are largely consistent with the estimates from the latest and third nationwide seroprevalence study.For wave 1 our estimate for the national IFR1 estimate of 0.032% (95% CrI 0.029–0.035%) and IFR2 estimate of 0.183% (95% CrI 0.18–0.186%). This pattern is consistent with wave 2 CFR being estimated at 0.845% (95% CrI 0.840–0.849%), 59% of wave 1 estimate.In wave 2, using the same model we see a stark contrast with wave 1, with case and death underreporting factor estimates escalate to 26.73 (95% CrI 24.26–28.81) and 5.77 (95% CrI 5.34–6.15) respectively, leading to IFR1, IFR2, CFR for waves 1 and 2 for 20 states in India with large case/death counts.Figure 1 estimate of 0.06% and IFR2 estimate of 0.24%. Detailed numerical estimates of underreporting factors across states for waves 1 and 2 are presented in Additional file The composite CFR as of May 15 stands at 1.1%. The estimate for total (reported + unreported) cumulative case count for waves 1 and 2 combined is 491.73 (95% CrI 453.03–524.56) million, while the estimated number of total (reported + unreported) deaths is 1216.35 (95% CrI 1154.21–1272.70) thousand. This leads to a combined IFRDespite accounting for underreported deaths, the large number of asymptomatic/undetected infections  indicate a lower IFR in India in comparison with other Western countries. A meta-analysis across the world places the pooled mean of IFRs at 0.68% (95% CI: 0.53–0.82%)   also got vaccinated during wave 2. However, this hypothesis about reduced fatality rates in wave 2 cannot be verified without more granular, age-sex stratified nationwide time-series data on case and death counts, which is currently unavailable.We do not have a rigorous way to validate the extent of underreporting of deaths. An excess death calculation based on historical mortality data is infeasible at this point due to absence of all-cause-mortality data in the last three years from India. India has a very young population with only 6.4% in age group 65 + (compared to the US where this proportion is 16.5%) so a comparison of overall IFR between India and say the US is not fair, and only age-specific IFRs should be calculated and compared when more data become available. We do recognize that wave 2 information is appreciably incomplete, and the estimates will change as we have more complete information on deaths. For example, while our wave 2 analysis period ended on May 15, the highest daily number of deaths (4529 daily new deaths) were reported shortly after on May 18. Thus, our analysis presents an updated but incomplete picture of wave 2.Additional file 1: Figure S1. Schematic diagram for the SEIR-fansy model with imperfect testing and misclassification. Figure S2. Estimated first wave underreporting factors for cases and deaths associated with SARS-CoV-2 for states in India. Figure S3. Estimated first wave underreporting factors for cases and deaths associated with SARS-CoV-2 for states in India. Table T1. Summary of the different metrics for the states and the nation for wave 1, on 31st January, 2021. Table T2. Summary of the different metrics for the states and the nation for wave 2, on 15th May, 2021. Table T3. Summary of the different metrics for the states and the nation for waves 1 and 2 combined, on 15th May, 2021. Table T4. Parameter values and descriptions for the SEIRfansy model.


The Y-axis intercept value was the metabolic energy requirement for maintaining the lives of the fattening Korean black goats. It was calculated to be 108.76 kcal/kg BWp = 0.945) were not affected by energy levels, but metabolic energy intake  and average daily gain  were significantly increased at higher energy levels. Nutrient digestibility was similar in the treatments, but crude fat digestibility increased with the addition of protective fat powder (p = 0.001). The energy required for fattening the castrated Korean black goats was estimated using the correlation between metabolic energy intake per dietary body weight and average daily gain per dietary body weight. The Y-axis intercept value was calculated to be 108.76 kcal/kg BW0.75 , which was the metabolic energy requirement for maintaining the lives of the fattening Korean black goats. The estimated energy requirements of the black goat can improve specification techniques, such as the energy level and the amount of feed supply required for domestic black goats.Twelve adult (10 months old) castrated Korean black goats, with an average initial body weight of 24.98 ± 3.7 kg, were used in this experiment to determine their maintenance energy requirements. Dry matter intakes (g/d,  Profitable feeding standards need to balance livestock nutrient requirements against the financial outlay of feed purchases made by farmers within the native environment of Korea. Optimized nutrient supply is indispensable for improving productivity, and its accuracy is an index in evaluating the competitiveness of the livestock industry. Feeding standards for livestock are necessary to establish optimal livestock growth stages and determine the appropriate amount of protein, energy, and mineral matter required. Productivity factors such as meat volume are closely related to environmental factors such as purchased feed . The ratMeasuring metabolism using a respiratory calorie meter, comparative massacre, and energy balance is often used to estimate nutrient requirements . RecentlCapra hircus coreanae) have traditionally been consumed as special food for health that helps strengthen the immune system, but this consumption style has recently changed them to common meat in Korea [Korean black goats  as a maintenance energy requirement for indigenous female and wether goats in their growth stages [All animal experimentation protocols were approved by the Konkuk University Institutional Animal Care and Use Committee (KU19005). Twelve adult (10 months old) castrated Korean black goats, with an average initial body weight of 24.98 ± 3.7 kg, were used with Latin squares in experimental design (4 × 4) to determine their maintenance energy requirements. The experiment was performed at a test farm located in Icheon City, Gyeonggi-do, from October 28 to December 30, 2016. The experiment consisted of 4 treatments , which were based on NRC’s recommendation of 108 kcal of body weight scaled at 75%  was set as the final body weight. The amount of intake of feed was estimated by subtracting the residual quantity before the next feeding from the whole amount of the first feeding.The feces of the black goats were collected and analyzed to investigate the digestibility of the samples. During the collection of manure, the total amount of manure per individual black goat was weighed and recorded. Fecal matter was collected in a plastic bag and vacuum-sealed. After each treatment, the total amount of feces samples collected per individual during the collection period was thoroughly mixed. The samples were then transferred to the laboratory, dried, and stored in an oven at 65 °C. The experimental diets (TMRs) were also dried and stored in an oven at 65 °C, and crushed to pass through a 1 mm screen  for further analysis.To evaluate the feed value of the experimental diet, samples were collected during each experimental period. The results of the composition analysis of the experimental diets are shown in All statistical analysis, except estimating the maintenance energy requirements, was performed by Tukey’s test using SAS software 9.3 . The analysis used a randomly extracted whole block ANOVA to compare the results of 4 treatment groups. For estimating the maintenance energy requirements, a regression analysis by using correlation between average daily gain (ADG) and metabolizable energy intake (MEI) was performed using the PROC REG method of the SAS program. All data were calibrated using metabolic weight.p = 0.945). DM intake generally depends on the type of feeds and individual characteristics of animals. According to previous studies conducted by Ranjhan [The effect of energy levels on body weight, feed intake, and ADG on fattening castrated Korean black goats is shown in  Ranjhan  and Lu [ Ranjhan , the DM  Ranjhan . However0.75. The T2 group was calculated at +5% to 113.4 kcal/kg BW0.75, the T3 group was calculated at +10% to 118.8 kcal/kg BW0.75, and the T4 group was calculated at +20% to 129.6 kcal/kg BW0.75. MEI during the experiment was therefore between 1233.9 ± 129.2 kcal/d and 1478.0 ± 165.0 kcal/d for the higher energy requirement levels (p = 0.002). The ADG was 16.3 ± 2.7 g/d for T1, 21.2 ± 8.1 g/d for T2, 29.5 ± 18.6 g/d for T3, and 65.9 ± 20.9 g/d for T4 (p = 0.001). These results show that the amount of ADG increased as MEI increased in the maintenance of the black goats in this study. In a similar study of Spanish goats, the metabolizable energy level of feed was 2.1–2.7 Mcal/kg, the ADG was 66.6–81.8 g/day [We used the regression equation estimation method of the correlation between ADG and MEI ,7. Indiv.8 g/day , and thep = 0.001). Increased DMI in ruminants may cause digestibility in the rumen to drop because of an increased rate of ruminal passage [p = 0.001) in this study. Thus, digestibility was higher in the feed supplemented with protected fat powder. The EE digestibility in this study was similar to that in a report on oil being added to a concentrated feed mixture containing 7:3 alfalfa and hay, where digestibility was 63.48% for an oil-free feed, 82.88% for a soybean oil supplement, and 82.37% for a corn oil supplement [The apparent nutrient digestibility in castrated black goats fed at different energy levels is shown in  passage . Howeverpplement . Generalpplement ,25,26. I0.75; T2, 113.4 kcal/kg BW0.75; T3, 118.8 kcal/kg BW0.75; T4, 129.6 kcal/kg BW0.75) and ADG per dietary body weight are indicated in 0.75 . The amount of energy required for maintenance varies depending on age, sex, breed, and breeding environment [0.75 for growing indigenous or local goats with weaning at 1.5 years of age [0.75 and 105.16 kcal/kg BW0.75 [0.75 for maintenance [0.75 and 101 kcal/kg BW0.75 during growth and mature periods, respectively, for female and wether goats [The results of estimating the energy requirements for fattening castrated Korean black goats using the correlation between MEI per dietary body weight (er goats  is presuer goats  suggeste0.75 in a tropical climate and 105.90 kcal/kg BW0.75 in a temperate climate. Nutrient management depend on environmental temperature is very important. Livestock stress due to too high or low temperatures may cause reductions of feed intake. Therefore, feed should contain energy sources with high-energy utilization rates and should supply appropriate levels of energy. Small ruminants in tropical climates appear to have higher metabolizable energy requirements for maintenance compared with those in temperate climates.Energy requirements for maintenance also differ with seasonal and temperature changes ,29,30. A0.75 in this study, which is similar to the maintenance energy requirement for a tropical environment. However, the study was carried out from October 28 to December 30, during a winter climate. Goats have higher energy requirements in winter months than in other seasons to maintain their body temperature. For weight maintenance alone, higher energy supply needs to maintain body temperature in a low-temperature environment. As a result of the study, it should be considered that the maintenance energy requirements of Korean black goats can be greatly affected in the four seasons in Korea. Additionally, it can help to prevent animal feed waste in goat farms and baseline data to establish the Korean black goat feeding system. There should be further study on maintenance energy requirements of black goats according to seasonal energy needs to establish more specific information about energy requirements for the maintenance of Korean black goats.The maintenance energy requirement was calculated to be 108.76 kcal/kg BW


BackgroundAccurate estimation of the donor’s glomerular filtration rate (GFR) is crucial for not only ensuring the medical appropriateness of the donor but also for the prediction of future allograft performance. The aim of this study was to compare the GFR estimation formulas and 24-hour urine creatinine clearance with diethylene triamine pentaacetic acid (DTPA) renal scan GFR.Methods2 were included. GFR was calculated with modification of diet in renal disease (MDRD), Cockcroft-Gault (CG), chronic kidney disease epidemiology (CKD-EPI) equations as well as by 24-hour urine creatinine clearance. DTPA renal scan was done to record GFR findings. GFR was compared using analysis of variance (ANOVA) among different methods.This cross-sectional study was done at the Department of Nephro Urology Dialysis & Renal Transplantation, Bahawal Victoria Hospital, Quaid e Azam Medical College, Bahawalpur, Pakistan from September 2018 to September 2021. A total of 92 potential healthy live-related kidney donors of both genders, aged 18 to 60 years having body mass index below 35 kg/mResults2, respectively. Statistically significant differences existed between various methods of GFR estimation (p<0.001). Mean GFR as per DTPA renal scan findings was noted to be 97.32±9.39 ml/min/1.73 m2. Difference of 31.48±20.81, 27.37±21.1, 23.38±6.38, 15.52±37.52 was noted in estimated GFR (ml/min/1.73 m2) with CG formula, MDRD formula, EPI-CKD formula and 24-hour urine creatinine clearance respectively when compared with DTPA renal scan findings. The highest proportion of patients was seen with normal GFR with DTPA renal scan findings as 83 (90.2%) individuals while 24-hour urine creatinine clearance observed these to be 59 (64.1%), CG EPI-CKD formula 44 (47.8%), MDRD formula 39 (42.4%) and 40 (43.5%) with CG formula.Out of a total of 92 individuals, 49 (53.3%) were male and 43 (46.7%) female. Mean age and BMI were noted to be 34.62±10.57 years and 24.40±2.71 kg/mConclusionNone of the GFR estimation methods resulted in similar findings. With reference to the DTPA renal scan, 24-hour urine creatinine clearance was the closest GFR estimation followed by CKD-EPI and MDRD equations. Accurate estimation of the donor’s glomerular filtration rate (GFR) is crucial for not only ensuring the medical appropriateness of the donor but also for the prediction of future allograft performance. Researchers have pointed out higher GFR of the donors to be independently linked with better allograft outcomes . MultiplIn Pakistan, a study comparing the accuracy of GFR estimation formulas with 24-hour urine creatinine clearance among live kidney donors revealed that the accuracy of the MDRD formula was 49%, CG formula 42% and chronic kidney disease epidemiology (CKD-EPI) 78% [This cross-sectional study was done at the Department of Nephro Urology Dialysis & Renal Transplantation, Bahawal Victoria Hospital, Quaid e Azam Medical College, Bahawalpur, Pakistan from September 2018 to September 2021. Approval from Institutional Ethical Committee was acquired for this study as reference number QAMC/IRB/2020-416. Informed and written consent was acquired from all study participants and confidentiality of their data was ensured.2. All individuals having a history of primary renal or systemic diseases were excluded. Pregnant women or those who could not provide accurate timely urine collection were also not included. During the study period, a total of 92 individuals fulfilled the inclusion/exclusion criteria so they were included.Inclusion criteria were all potential healthy live-related kidney donors of both genders, aged 18 to 60 years having body mass index below 35 kg/mA detailed history was acquired from all study participants and a detailed physical examination was done to exclude any possible renal or related systemic illness. The height of the individuals was measured using measuring tape while weight was measured with an electronic weighing scale and BMI was calculated. A venous blood sample was taken by a well-trained phlebotomist in a vacuum tube whereas serum creatinine was measured by adopting an automated chemistry analyzer. GFR was calculated with MDRD, CG as well as the CKD-EPI formulas. All participating individuals in this study were asked to collect urine for 24 hours in a container provided by the study institution. These urine collections were sent to the institutional laboratory and GFR based on 24-hour urine creatinine clearance was noted. For the DTPA renal scan, all individuals were fully hydrated (300 to 500 ml of regular drinking water) 20 to 30 minutes prior to the renal scan. All individuals were placed in the supine position with the probe placed at the lower back and SPECT field of view involving both kidneys and the bladder. Immediately following intravenous injection of 5 mCi Tc-99m DTPA, images were taken in the front and rear positions of the dual probe. Following this, an empty syringe was collected for six seconds to obtain the residual drug count. The region of interest (ROI) was drawn manually on the frame of the kidney and the semi-lunar background was placed around the lower, outer renal margin. After the patient’s data about weight and height were input into an online computer, the GFR was automatically calculated by commercially available software according to the Gate’s algorithm.A special proforma was designed to record all study data. Statistical Package for the Social Sciences (SPSS), version 26.0  was used for data analysis. Quantitative data like age, BMI and GFR were expressed as mean and standard deviation whereas qualitative data like gender were expressed as frequency and percentage. GFR was compared using analysis of variance (ANOVA). A P-value below or equal to 0.05 was considered statistically significant.2 ranging between 18.1 and 35 while 53 (57.6%) individuals had BMI below or equal to 25. Mean serum creatinine was observed to be 0.69±0.14 ranging between 0.40 and 0.92 mg/dl. Table 2 and it was found that statistically significant existed in between various methods of GFR estimation (P<0.001).Out of a total of 92 individuals, 49 (53.3%) were male and 43 (46.7%) female. Mean age was noted to be 34.62±10.57 years ranging between 18 and 57 years while 55 (59.8%) patients were aged below or equal to 35 years. Mean BMI was noted to be 24.40±2.71 kg/m2. Difference of 31.48±20.81, 27.37±21.1, 23.38±6.38, 15.52±37.52 was noted in estimated GFR (ml/min/1.73 m2) with CG formula, MDRD formula, CKD-EPI formula and 24-hour urine creatinine clearance, respectively, when compared with DTPA renal scan findings. Figure Mean GFR as per DTPA renal scan findings was noted to be 97.32±9.39 ml/min/1.73 mThe classic approach to measuring GFR has been the measurement of insulin clearance which is hectic and not feasible in daily practice routines. Due to these reasons, various equations aimed to estimate GFR have been developed. The oldest well-known method of GFR calculation has been the CG equation which actually calculates creatinine clearance rather than GFR. The late 1990s saw the first description of the MDRD equation come to light, which consisted of six variables and revolutionized GFR estimation. More recently, the next advancement in GFR estimation was seen with the help of the CKD-EPI equation . This st2. Difference of 31.48±20.81, 27.37±21.1, 23.38±6.38, 15.52±37.52 was noted in estimated GFR (ml/min/1.73 m2) with CG formula, MDRD formula, CKD-EPI formula and 24-hour urine creatinine clearance, respectively, when compared with DTPA renal scan findings. As there are numerous ways to measure GFR directly, these different methods often yield measurements that do not agree with each other. For example, examination of the Bland-Altman plot of a study of nonradioactive iohexol (plasma) versus insulin (urinary) clearance suggested that the two readings often disagreed by as much as 20% [2 higher than insulin-measured GFR (127.1±12.4 versus 108.3±14.1 ml/ min per 1.73 m2) [2. The 24-hour urine creatinine clearance is popularly regarded as the most adopted method for estimation of GFR and some researchers have compared it with other formula equations for the estimation of GFR establishing the authenticity of 24-hour urine creatinine clearance [Buchler M et al and Fotopoulos A et al in their findings shared that DTPA renal scan is the best way to get GFR estimation and has an excellent correlation with the gold standard techniques ,12. In th as 20% . Another1.73 m2) ,17. As plearance . The moslearance . The reaStar et al shared that serum creatinine concentration is influenced by muscle mass, dietary protein intake, and gender and age variations, and these factors can have limiting effects on the true estimation of GFR adopting creatinine-based approaches . Among iOne of the limitations of this study was that being a single-center study with comparatively small sample size, our findings cannot be generalized. We were unable to take note of renal volumes among study individuals.None of the GFR estimation methods resulted in similar findings. With reference to DTPA renal scan, 24-hour urine creatinine clearance was the closest GFR estimation followed by CKD-EPI and MDRD equations. It is important to check the validity of various methods of GFR estimation among different sets of populations. Further studies should be planned to evaluate the validity of commonly adopted methods for the estimation of GFR in live kidney donors.


Gas accumulation in human joint spaces has been generally described as the vacuum phenomenon (VP). To date, the sacroiliac joint VP has been associated mostly with pathological, particularly degenerative conditions .The study aimed to examine the characteristics of the physiological form of VP and its radiological patterns in a sample of pediatric patients.A sample of seventy patients between 0 and 17 years old  were included in the study. Sample VP cases was evaluated according to types, age group, anatomic localization, gender, and sides. RESULTS: Two (2.9%) of sample children had degenerative VP, with 24 (34.2%) of patients demonstrating physiological VP in the sacroiliac joints. VP rates significantly increased after nine years of age (p < 0.01) and 83% of physiological VP cases were determined to be bilateral.Although degenerative VP is a rare entity in children, non-pathological VP can be a more common aspect of sacroiliac anatomy. Although sacroiliac VP is frequently an underreported or omitted finding in imaging studies, this condition may be clinically important as a clue for other degenerative diagnoses. Normal variants of VP may be clinically important in children since they may mimic inflammatory and infectious pathologies during magnetic resonance imaging and computed tomography images. Gas accumulation in the joint space has been generally described as the vacuum phenomenon (VP).In 2016, Takata et al. evaluated the relationship between sacroiliac pelvic morphology and VP in all age groups.During musculoskeletal system evaluations of pediatric patients, MRI is often preferred instead of CT to avoid excess radiation risks. However, since gas is seen at different signal intensities on MRI, this preference may cause the VP to be confused mistakenly with pathological situations.Ultimately, the study aimed to describe the characteristics of the physiological VP and its radiological patterns in a sample of pediatric patients. The authors intended to systematically identify likely rates of VP in the SIJ and examine overall radiological characteristics of physiological forms of VP in the pediatric population.Before data collection, this study was approved in 2020 by the authors’ university Human Research Ethics Committee. Eligible patients who had received CT scans between January 2016 and June 2020 for various indications were retrospectively evaluated using images obtained from accessible picture archiving communication systems (PACS). Sacroiliac joint VP was initially detected in a total sample of 79 pediatric patients. Five (6.3%) patients were excluded from analyses for the following medical reasons: one patient had a Wilms tumour, one had lymphoma, and three had a previous history of pertinent trauma. In addition, four CTs with artefacts were also excluded due to not being appropriate for evaluation.In total, 70 children, male, 34 (48.5%) and female, 36 (51.4%); mean age, 11.4 ± 5.54) were eligible for study evaluation. The pre-study minimal sample size power calculations that had been conducted by the authors using G-power*3 software indicated that a necessary sample of 45 patients would be required to attain 95% power, 0.05 Alpha and 0.5 effect size in a one-way calculation .Sample children’s CT scans had each been performed with a 256-slice multi-detector CT scanner . Sacroiliac joints were individually visualized in coronal, axial and sagittal planes. Oral sedatives were administered before the CT procedure [chloral hydrate is 50–100 mg/kg (up to a maximum of 2.0 g)]. The tube voltage  and applied radiation dose (2.3 mSv to 19.9 mSv) varied depending on the weight of each child. All CTs were conducted in a supine position. Other CT scan parameters were as follows: rotation time, 0.35s; thickness, 1mm; FOV (field of view) 30-40 cm.Each study image was assessed by the two blinded radiologists (first author ED and third author SA). Each radiologist independently evaluated the CT images on the coronal, axial and sagittal planes. In case of contradictory results, the images were evaluated together by both radiologists. Imaging evaluations were made at the workstation with a high-resolution medical monitor in soft-tissue window , bone window  as well as the lung window  to distinguish air more clearly from soft tissue and bone. The presence of gas  was considered positive for VP in the SIJ .Figure 2).Patient results were classified according to age groups  as well as gender . Data according to the presence of SIJ VP were enlisted as right, left and bilateral  analysis was used to evaluate the relationship between variables. P values < 0.05 were statistically significant.Study data were stored using a Microsoft Office Excel spreadsheet . The authors used software  for statistical analyses. Continuous variables were expressed as mean ± SD (standard deviation) values. Qualitative variables were totalled and calculated as percentages. All data were statistically compared according to gender. The Student’s t-test procedure was used for analysis of the mean of normally distributed values. Age groups were compared using the Student’s t-test and Analysis of Variance (ANOVA) test. Pearson chi-square . The mean age of female patients was 11.83 years ± 5.55 years; 0-17 years . In total, the overall mean sample age was 11.4 years ± 5.54 years; 0-17 years . Two male patients, who are 15 years and 16 years old, both with obesity, had degenerative VP. Surface irregularity and sclerosis were present in their SIJ. VP was detected in 24 (48.6%) patients without any accompanying finding in favour of degeneration. These patients were included in the physiological VP subgroup. In total, 26 of 70 (37.1%) of the patients had VP. Two (2.9%) of 70 children were concluded to have degenerative VP, while 24 (34.2%) possessed physiological forms of VP.Respectively the physiological VP distribution according to age groups as follows:0-4 years old: None of the sample patients had VP.5-8 years old: 9.1% (one of 11) of all patients and 25% (one of 4) of the female patients had VP while none of the male patients had VP in this age group. The VP was bilateral in this one female patient.9-11 years old: 66.7% (4/6) of the children in this age group had VP. The percentages were equally distributed between both genders. 33.3% (1/3) in males had bilateral VP while 33.3% (1/3) of them unilateral. None of the female patients had unilateral VP in this age group. 66.7% (2/3) of the female patients had bilateral VP.12-14 years old: Two (50%) of the patients in this age group had VP, both males.15-17 years old: Two patients had degenerative VP in this age group. Totally, 45.9% (17 of 37) of the patients had SIJ VP. 43.8% (7 of 16) of male patients and 47.6% (10 of 21) of the female patients had VP. For male patients, 12.5% 2 of 16 had degenerative VP. In the evaluation of physiological VP, 7.4% (1 of 14) of the male patients had unilateral VP while 42.9% (6 of 14) of the had bilateral VP. 9.5% (2 of 21) of the female patients had unilateral VP while 38.1% (8 of 21) of the female patients had bilateral VP.  .Both patients with VP in each gender subgroups and the total sample were separately evaluated using the Pearson chi-square (χ2) analysis. P value was also highly significant (p < 0.01). In summary, there was an adequate imaging threshold for VP found when categorizing patients by this age parameter. However, “under and over nine” age group images were separately heterogeneous and did not regularly demonstrate VP increases. No statistically significant differences were found in the comparisons between 0-4 years and 5-8 years, between 9-11 and 12-14 years, and between 12-14 years and 15-17 years.Children who were under nine years of age and over nine years were stratified into two subgroups and compared with 2) analysis. There were no overall statistically significant differences found between gender subgroups (p = 0.603) (VP were compared across gender using Pearson’s chi-square (χ= 0.603) .SIJ VP (p < 0.05).In the total sample evaluation of physiological VP performed regardless of parameter groups, VP was bilateral in 18 (75%) of 24 cases. The authors also evaluated pattern asymmetry in sample children who had bilateral VP. This pattern was symmetrical in 12 (66%) of 18 patients and asymmetrical in 6 (33%) of 18 patients. Six (25%) of 24 remaining children had unilateral VP, 4 (66.7) of six on the right side and 2 (33.5%) of six on the left side. There was a statistically significant difference between genders according to the symmetry of 2) test (p < 0.05)  .VP in pediatric patients is a frequently neglected radiological finding. One of the reasons this condition is not often described in radiology reports is that it is generally considered unimportant. Radiologists are not inclined to dwell on describing results that cannot be used.If clinicians encounter a fracture, the presence of VP may suggest an underlying chronic process.SIJ is the body’s largest joint.symphysis-like and the lower third the synovial.The As suggested by these results, VP is not always a stable condition. In fact, it is frequently a phenomenon of a pressure/solubility equilibrium. The presence or absence of VP may change according to different physical conditions in the radiological examinations performed at different times of childhood and adolescence.VP will rarely induce symptoms. A condition called pneumatic nerve root compression associated with VP is a cause of pain.Pathological VP is the only condition confused in the differential diagnosis of physiological VP in CT imaging, as it can distinguish accompanied degenerative findings.Our study had some limitations. Our study conclusions have been drawn from a smaller retrospective convenience sample and limited to CT scan images. We acknowledge that the imaging and diagnostic resources available to clinicians may vary from our Turkish university setting.Physiological VP is one of the more common aspects of sacroiliac anatomy in the pediatric age group. Although SIJ VP is an underreported or omitted finding in imaging studies, this condition may be clinically important as a clue for other degenerative diagnoses. Additional studies with larger pediatric sample are required to further examine this condition. These results could be used for differential diagnosis from pathologies in MRI evaluation.The authors declared that this case has received no financial support.The authors have no competing interest.


WHO defines adolescent pregnancy as any pregnancy from a girl who is 10-19 years of age, the age being defined as her age at the time the baby is born. Globally, adolescent birth rate is 44 per 1000 women aged 15-19 years whereas 33 per 1000 in South East Asian region. The main objective of the study is to find the prevalence of adolescent pregnancy in a tertiary care hospital.st January 2018 to 30th June 2018. Using the convenient sampling technique, 2688 samples were studied and the descriptive statistical analysis was done.A descriptive cross-sectional study was conducted in Department of Obstetrics and Gynecology, Nobel Medical College and Teaching Hospital, Biratnagar over a period of six months from 1The prevalence of teenage pregnancy was found to be among 143 (5.3%) [5.3%±0.85% at 95% Confidence Interval]. Maximum adolescents of 95 (66.4%) presented at gestational age between 37 to 40 weeks. Regarding contraception, only 2 (1.4%) of teenage mothers had used Injectable Depo Provera.Adolescent pregnancy in developed countries is usually outside of marriage and carries a social stigma but in the context of developing countries it usually happens within marriage and half of them are planned reflecting educational status and contraception knowledge. Effective interventions need to be developed like strict enforcement of laws prohibiting teenage marriage. WHO defines adolescent pregnancy as “any pregnancy from a girl who is 10-19 years of age”, the age being defined as her age at the time the baby is born. Globally, adolescent birth rate is 44 per 1000 women aged 1519 years whereas 33 per 1000 in South East Asian region. It has been projected that in 2015-2020, more than 1 in 25 adolescent girls aged 15-19 years will give birth.Adolescent pregnancy has increased rapidly due to unprotected sexual activities, early marriage, illiteracy, low socioeconomic status, poor awareness about contraceptive need and choices.This study aims to find out the prevalence of adolescent pregnancy in a tertiary care hospital of Nepal.st January 2018 to 30th June 2018. Ethical clearance was taken from theThis descriptive cross-sectional study was conducted in Department of Obstetrics and Gynecology, Nobel Medical College and Teaching Hospital, Biratnagar over a period of six months from 12 × pq/e2Sample size (n)=Z2 × 0.5 × (1-0.5) / (0.02)2     =(1.96)     =2401Institutional Review Committee. The sample size was calculated as per below formula:Z= 1.96 for confidence interval at 95%p= prevalence, 50%q=1-pe= margin of error, 2%where,Keeping non-response rate at 10%, the final sample size is 2641. Convenient sampling technique was applied. Total 2688 samples were taken for the study to minimize the possible biases (information bias and interviewer's bias) and to make it more scientific.All pregnant women who delivered baby in this hospital during study duration were included in the study after their consent. Cases planned for medical termination of pregnancy were not included. Information was noted in a well-structured proforma.Maternal outcomes recorded were anemia, preterm delivery, hypertensive disorders in pregnancy, operative deliveries with indications of caesarean section, postpartum complications and maternal mortality. Perinatal outcomes recorded were low birth weight, stillbirth, indications of neonatal admission and neonatal death. The data were entered in Microsoft Excel and analyzed using SPSS software version 23.Out of the 2688 deliveries, the prevalence of adolescent pregnancy was 143 (5.3%) [5.3% ±0.85% at 95% CI]. Mean age was 18.4 years (ranges from 16 to 19 years). Out of them, 57 (39.9%) had early marriage at the age of 18. Most of the adolescents were unbooked, from low socioeconomic status and 129 (90.2%) were primigravida. Maximum adolescents of 95 (66.4%) presented at gestational age between 37 to 40 weeks and postdated pregnancy was 28 (19.6%). Among them, the caesarean section was done in 42 (29.4%) .The most common indication for cesarean section was fetal distress in 18 (43%), Cephalopelvic Disproportion (CPD) in 8 (19%) followed by failed induction in 5 (12%) .About 67 (46.8%) of adolescents mothers had maternal complications. The most common complication was Premature Rupture of Membrane (PROM) in 20 (14%) followed by anemia in 19 (13.3%), hypertensive disorders in pregnancy were observed in 9 (6.29%) and there was no maternal mortality in the study period .Regarding contraception, only 2 1.4%) of teenage mothers had used Injectable Depo Provera. The mean birth weight of newborn was between 2.5 to 4 kg, 117 (81.8%) being majority appropriate for the gestational age i.e. 2.5 kg or more. Only 25 (17.5%) were low birth weight whereas 20 (14%) accounting for preterm deliveries. There was one case of stillbirth and 22 (15.4%) were admitted in NICU for Meconium Aspiration Syndrome (MAS), birth asphyxia, respiratory distress syndrome and Transient Tachypnea of Newborn (TTN)  and 4. O% of teen8 Similarly, results that of Subedi A. et al5 in 2018 showed incidence of 6% and Suwal A. et al in 2012 showed 6.85% but 2.81% higher than Seneesh KV et al. The incidence of teenage pregnancy is highest in Bangladesh 35% followed by Nepal 21% and India 21% in the context of South Asia. However, in contrast to this study the incidence of teenage pregnancy was as high as 9.7% by Kayastha et al.Adolescent pregnancy is a public health problem and this period is a distinct and unique physical and developmental stage in woman's life. Currently 40% of the population in Nepal is under the age of 18 years . In Nepal, 17% of adolescent aged 15-19 are already mothers or pregnant with their first child. The prevalence in Nepal have been reported varyingly. The prevalence of teenage pregnancy in the current study is 5.3% which is similar to 5.10% in Yasmin et al.5According to NDHS 2016, the median age at first marriage for women age (25 to 49 years) is 17.9 years. Women initiate sexual activity at the same time of marriage at age 17.9 years. More than half (52%) of women are married by age 18. In our study, meanage of marriage was 18.4 years (ranges from 16 to 19) and majority of adolescent mothers (52.4%) were at 19 years of age similar to that of Subedi et. al.11 The higher proportion of normal vaginal delivery could be due to smaller babies (17.4%) in this study.Most of the teenagers in the study were unbooked, from low socioeconomic status reflecting poverty and poor prenatal care. Majority of them were primigravida 90.2% as expected. Regarding the mode of delivery 65.7% underwent normal vaginal delivery and 29.4% of them delivered by cesarean section. Findings similar to this study have also been shown by studies of Mukhopadhyay P. et al. in 2010.8 and Mukhopadhyay P. et al.11 One of the proposed explanations for these adverse birth outcomes are biological immaturity. Teenage pregnancy has emerged as a burden to the social infrastructure due to its catastrophic consequences. Teenage mothers were nearly three times more at risk of developing anemia and delivering preterm. Derme and his colleagues reported that PROM was the most common maternal complication which is similar to our study.13 In this study,13.3% patients were anemic and 14% had preterm delivery. Only 1.4% of teenage mothers used the temporary methods of contraception which could be the reason for early childbearing in teenagers. There was no case of maternal mortality in our study. 17.5% of teenage mothers had low birth weight which is similar to the findings reported by Yasmin et al. (16.86%).8 Swati Mahajan reported the incidence of LBW to be 19%.14 There was one case of stillbirth and babies of 15.4% of teenage pregnancy were admitted in NICU to rule out MAS followed by birth asphyxia, respiratory distress syndrome and TTN.Several studies from Nepal have documented poorer outcomes for children born to adolescent mothers compared to older mothers. The most common indication of cesarean delivery in this studywasfetal distress followed by CPD similar to the findings of Yasmin et al.The primary limitation of this study was that since this study was conducted in a peripheral tertiary-care hospital and there were maximum chances of referred cases and it might not truly reflect the current situation in community basis. Another important aspect is that the exact quantification of adverse perinatal outcomes of teenage pregnancy might have been biased due to unequal distribution of sociodemographic characteristics and also because the delayed complications that can occur beyond 48 hours could not be observed because of inadequate follow up protocol.The present study attempts to emphasize on adolescentfriendly health care services including regular antenatal checkup, rest, adequate sleep and appropriate counseling. Teenage pregnancy characterizes a high risk group because of the double burden of reproduction and growth and is associated with social issues including lower educational levels and poverty. Adolescent pregnancy in developed countries is usually outside of marriage and carries a social stigma but in the context of developing countries it usually happens within marriage and half of them are planned reflecting educational status and contraception knowledge.Effective interventions need to be developed like strict enforcement of laws prohibiting teenage marriage. Contraceptive practice need to be promoted in order to delay future pregnancy and we need to do lot in this field to improve the contraceptive prevalence rate in Nepal.None.


AimTo identify the types of glaucoma and associated comorbidities among patients attending the ophthalmology clinic at King Abdulaziz Medical City (KAMC) in Jeddah.MethodsA cross-sectional study that included all glaucoma patients at KAMC in Jeddah between June 1st, 2016 and November 30th, 2020. Data were collected through retrospective chart review from the electronic medical record system (BestCare) and utilized a structured data collection sheet.ResultsA total of 283 patients met the inclusion criteria. The most common type was primary open-angle glaucoma  followed by secondary glaucomas  then childhood glaucoma and primary angle-closure glaucoma . The majority of secondary glaucoma cases were due to neovascular glaucoma , followed by phacomorphic glaucoma (17.9%) and phacolytic glaucoma (10.3%). Hypertension (60.8%) and diabetes (58.3%) were the most prevalent systematic comorbidities, and cataract (49.1%) was the most prevalent ocular comorbidity.ConclusionPOAG was the most common glaucoma type, followed by SG, CG, and PACG. Among secondary glaucoma types, neovascular glaucoma was found to be the most common subtype. Hypertension was the most prevalent comorbid condition. Blindness is one of the major public health concerns, and as the size of the population increases, this issue will exert a huge burden on public health . GlaucomGlaucoma is regarded as the leading cause of irreversible blindness and the second leading cause of blindness worldwide by the World Health Organization (WHO) ,7. It isVisual impairment continues to be a major public health concern with a substantial impact on all aspects of quality of life, including physical functioning, emotional distress, and socioeconomic loss . The pauThis cross-sectional study was conducted at KAMC in Jeddah, Saudi Arabia. It included patients diagnosed with glaucoma attending general ophthalmology clinics between June 1st, 2016 and November 30th, 2020, using a consecutive sampling technique. Patients with other types of optic neuropathy were excluded from the study. A retrospective chart review was conducted using electronic medical records and a structured data collection sheet. The data collection sheet consisted of socio-demographic variables like age, gender, and BMI. Moreover, clinical variables such as glaucoma type and etiology, visual acuity, treatments, and comorbidities, were recorded. Using the International Council of Ophthalmology classification, the best corrected visual acuity (BCVA) was categorized into normal vision as 6/6 - 6/7.5, near-normal vision as 6/9.5 - 6/18, moderate vision loss as 6/21 - 6/48, severe vision loss as 6/60 - counting fingers (CF), near-blindness is hand motion (HM) - light perception (LP), and blindness as no light perception (NLP) [All patients’ data were kept confidential, and ethical approval was obtained from the Institutional Review Board at King Abdullah International Medical Research Centre (KAIMRC), National Guard Health Affairs (NGHA), Jeddah, Saudi Arabia .2 (25-33), and intraocular pressure of 16 mmHg (13-20) in both eyes  of which were males, and 150 (53%) were females. Our sample noted that 59.9% of the patients had bilateral disease, while 40% had unilateral disease (p < 0.001). The median (IQR) for age was 66 years (57-74), ranging from two months to 101 years old, BMI 29 kg/mThe most common glaucoma types were primary open-angle glaucoma  followed by secondary glaucoma SG; 26.5%), then childhood glaucoma and primary angle-closure glaucoma . Normal-tension glaucoma (NTG) accounted for 2.5%, absolute (unspecified) glaucoma accounted for 2.1%, and both juvenile and mixed mechanism glaucoma represented 0.7% and 0.4% of the sample, respectively . Other types of secondary glaucoma included phacomorphic glaucoma (17.9%) and phacolytic glaucoma 10.3%). Additional types of glaucoma that were seen less frequently included angle recession glaucoma 2.6%), uveitis glaucoma (2.6%), malignant glaucoma (2.6%), post-traumatic glaucoma (1.3%), and aphakic glaucoma (1.3%) , diabetes 58.3%), obesity (43.1%), and dyslipidemia (33.6%). Cataract (49.1%) was the most prevalent associated ocular comorbidity. Other comorbidities were also noted in glaucoma patients but were less frequent, such as ischemic heart disease (15.2%), renal diseases (14.1%), hypothyroidism, and cerebrovascular disease (10.6%). Further details are shown in Figure %, obesitAnalysis of visual acuity showed that most patients had a moderate loss of visual acuity (26.87%), followed by near-normal visual acuity (19.22%), and followed by severe loss of visual acuity (18.15%). Most of the children were able to fix and follow objects with their eyes (0.8%) and blink to light (0.7%), while only a few of them couldn't fix and follow objects (0.5%). Details regarding visual acuity impairment are found in Table Control of intraocular pressure was achieved by medical, laser, or surgical methods. In terms of medical therapy used in our sample, beta-blockers were the most commonly used agents (72%), followed by carbonic anhydrase (CA) inhibitors (71.3%). Prostaglandins and ⍺2-agonists were used by 61.4% and 60.7% of patients, respectively. Moreover, laser peripheral iridotomy was utilized in 7.4%, while cyclocryocoagulation was used in 4.9%. Regarding surgical procedures, trabeculectomy was performed in 50.1% of patients. Further information is represented in Table The present study demonstrates the glaucoma profile in patients who presented to KAMC in Jeddah. In addition, we analyzed the pattern of glaucoma among the patients to estimate the prevalence of different types of glaucoma, comorbidities, and clinical characteristics using internationally recognized glaucoma definitions.No statistically significant difference was noted between males and females in our study as 53% of the sample were female compared to 47% males . This contrasts with a local study which showed a significant difference between genders with a female predominance as 59% of their sample were females  . FurtherTypesOur study showed that POAG is the predominant subtype, followed by secondary glaucoma types, childhood glaucoma, and PACG. The results are consistent with studies that have been conducted in western countries which reported POAG to be more prevalent (89.0%) than PACG . HoweverComorbiditiesMultiple studies have shown hypertension to be among the most common comorbid conditions with glaucoma, consistent with our findings ,15. HoweAnother common comorbidity in our sample was diabetes mellitus, as seen in 58% of patients, which is higher than local studies in Riyadh and Qassim, which reported a prevalence of 14.9% and 32.8%, respectively . The mecDyslipidemia is among the comorbidities commonly associated with glaucoma and was seen in approximately 33.6% of our sample. This finding is similar to other global studies but higher than local reports ,15. HoweVisual acuityOur study reported and categorized the best-corrected visual acuity based on the severity of visual impairment. Each category had an equal distribution between the right and left eye. A majority of the patients in our study had a functional vision that was distributed between patients who had a near-normal vision (19.22%) and normal vision (16.01%). However, 26.87% of the patients had moderate visual impairment. These findings are comparable to a local study that included 124 glaucoma cases which showed that most patients reported mild to no visual impairment (86.3%), which was defined as visual acuity equal to or better than 6/18 [LimitationsThis study was limited by multiple factors, including its small sample size and the retrospective single-center design, limiting the generalizability of results. Moreover, limited documentation in the clinical records is another shortcoming since multiple data were missing. Therefore, population-based studies with larger sample sizes are warranted to delineate better the prevalence and types of glaucoma among the Saudi population.Primary open-angle glaucoma was the most common glaucoma subtype affecting half of the patients included in this study. Secondary glaucomas were the second most common, and the majority of cases were found to be neovascular glaucoma. In addition, hypertension and diabetes were the most common reported comorbidities seen in over half the patients. Moreover, a significantly higher proportion of patients had bilateral disease compared to unilateral.


The Sustainable development goals, which focus strongly on equity, aim to end all forms of malnutrition by 2030. However, a significant cause of intergenerational transfer of malnutrition, anaemia in pregnancy, is still a challenge. It is especially so in the low- and middle-income settings where possible context-specific aetiologies leading to anaemia have been poorly explored. This study explores the prevalence of etiological factors significantly contributing to anaemia in pregnancy in Sri Lanka, a lower-middle-income country with a high prevalence of malnutrition albeit robust public health infrastructure.All first-trimester pregnant women registered in the public maternal care programme in the Anuradhapura district from July to September 2019 were invited to participate in Rajarata Pregnancy Cohort (RaPCo). After a full blood count analysis, high-performance liquid chromatography, peripheral blood film examination, serum B12 and folate levels were performed in anaemic participants, guided by an algorithm based on the red cell indices in the full blood count. In addition, serum ferritin was tested in a random subsample of 213 participants. Anaemic women in this subsample underwent B12 and folate testing.n = 451) were anaemic. Haemoglobin ranged between 7.4 to 19.6 g/dl. 331(10.6%) had mild anaemia. Haemoglobin ≥13 g/dl was observed in 39(12.7%). Microcytic, normochromic-normocytic, hypochromic-normocytic and macrocytic anaemia was observed in 243(54%), 114(25.3%), 80(17.8%) and two (0.4%) of full blood counts in anaemic women, respectively. Microcytic anaemia with a red cell count ≥5 * 106 /μl demonstrated a 100% positive predictive value for minor haemoglobinopathies. Minor hemoglobinopathies were present in at least 23.3%(n = 105) of anaemic pregnant women. Prevalence of iron deficiency, B12 deficiency and Southeast Asian ovalocytosis among the anaemic was 41.9% (95%CI 26.4–59.2), 23.8% (95%CI 10.6–45.1) and 0.9% (95%CI 0.3–2.3%), respectively. Folate deficiency was not observed.Among 3127 participants, 14.4% (95%CI 13.2–15.7, Even though iron deficiency remains the primary cause, minor hemoglobinopathies, B 12 deficiency and other aetiologies substantially contribute to anaemia in pregnancy in this study population. Public health interventions, including screening for minor hemoglobinopathies and multiple micronutrient supplementation in pregnancy, should be considered in the national programme for areas where these problems have been identified. Anaemia in pregnancy is a major public health problem as many countries across the globe are struggling to quantify, prevent and treat this condition. The global prevalence of this issue is estimated to be around 38%, while 58.1% of South Asian pregnant women are thought to be anaemic . HoweverAnaemia during pregnancy can adversely affect both the mother and the foetus. Severely anaemic pregnant women have a 2.36 times higher risk of death than other pregnant women  and are Traditionally the most typical cause of anaemia is iron deficiency, contributing to more than 50% of anaemia in pregnancy worldwide , 11. TheOther micronutrient deficiencies , hemoglobinopathies, red cell membrane disorders, and systemic causes ) also contribute to anaemia in pregnancy , 21. TheAs an example, folate deficiency is high in malaria-endemic regions and in countries where the staple food is not fortified with folate . PregnanVitamin B12 deficiency is highly prevalent in some countries of the Indian subcontinent, where 32% of first trimester pregnant women are reportedly B12 deficient . B12 defAnaemia due to hereditary conditions such as minor hemoglobinopathies or membrane disorders can be prevalent in some communities. For example, any variant of hemoglobinopathy is carried by 45.5% of the South Asian population . Having Successful control of anaemia in a pregnant woman requires alleviation of its aetiology. In many parts of the world, the focus of public health interventions to prevent and control anaemia in pregnancy is almost limited to controlling iron deficiency . MultiplDespite having a robust public health system catering for its population across the lifecycle, anaemia prevalence among pregnant women in Sri Lanka is 29.1% ) , resemblAmid the success of such strategies, other aetiologies gain prominence marking poor progress of anaemia control. Identification of aetiologies significantly contributing to anaemia in pregnancy in a particular community enables the implementation of policies and interventions to address them, leading to better control of anaemia and improved maternal and foetal outcomes. However, etiological assessment is often costly and less feasible in settings where the disease burden is highest, the LMICs. Categorising anaemia according to the red cell indices in the full blood count and using these categorisations to guide treatment and further assessment is helpful in the low resource settings.This study aims to determine the actual prevalence of anaemia and its’ aetiologies among first trimester pregnant women in Anuradhapura district, Sri Lanka. To our knowledge, this is one of the largest studies on early maternal anaemia in LMICs and the first Sri Lankan study that assess the contribution of several important aetiologies to anaemia in pregnancy, which therefore would provide data for specific preventive strategies in vulnerable populations.This population-based study was carried out as a part of the Rajarata Pregnancy Cohort (RaPCo) in Anuradhapura district, Sri Lanka . AnuradhPregnant women newly registered in the national pregnancy care programme from July to September 2019 were invited for the study. We selected first trimester pregnant women (up to the completion of 13 weeks of gestation) for this component. The detailed methodology has been explained elsewhere , 36.We hypothesised that causes of anaemia affecting at least 10% of anaemic pregnant women would be significant from a public health point of view. To detect an aetiology with a 10% prevalence , at least 425 anaemic pregnant women were needed to be included. Thus, according to the anaemia prevalence in the district, at least 1866 pregnant women were needed to be recruited.Invitation to participate in the study was sent to all eligible participants through their Public Health Midwife. From July to October 2019, a special clinic was conducted fortnightly at each health division , where the eligible participants were recruited consecutively. Altogether, 226 clinics were conducted across the district for participant recruitment.An interviewer-administered questionnaire and a physical examination to elicit clinical signs were used for data collection. In participants reporting a previously diagnosed minor hemoglobinopathy, the HPLC report was observed for verification. Venepuncture was done to collect whole blood and serum samples and to prepare peripheral blood films. All slides were prepared in the field, and the serum separation was done within 2–4 h of sample collection. Aliquots of samples were stored at -80 °C.We performed a full blood count for all the participants. Out of the calculated minimum sample, 10% was randomly selected for Serum ferritin testing to estimate iron status , 38. Per6_), minor hemoglobinopathy was suspected [According to current evidence, all the anaemic women  were classified into five mutually exclusive categories based on their red cell indices. When there was microcytic anaemia (MCV < 80 fl) with a high RBC index  was defined as having haemoglobin less than 11 g/dl . HaemoglSerum ferritin, Homocysteine, B12 and Folate assessments were performed in a commercial laboratory with external quality control methods. HPLC was performed at the thalassemia unit of Teaching hospital, Anuradhapura. Other investigations  were performed in a public health research laboratory with internal and external quality control. Samples for serum B12, folate and homocysteine were stored and transported refrigerated and covered from exposure to sunlight. They were analysed as soon as possible with a maximum stored time of 48 h.Data from the interviewer-administered questionnaire was entered directly into a cloud-based password secured database. Laboratory investigations data were later merged with the cloud data. The first author has manually verified a 20% of the full blood count data and all of the other laboratory investigation data used for this paper.Data analysis was performed using SPSS version 22 and Open Epi. The graphs were prepared using GraphPad Prism and Microsoft word. Fissures exact test was performed to compare the proportions of self-reported thyroid, liver, renal and autoimmune diseases among anaemic and non-anaemic pregnant women.Of the first trimester pregnant women registered in the public maternal care program in the district, 3127  were recruited for the anaemia study. The majority of the participants were ethnic Sinhalese (87%), and 31% were in their first pregnancy (Table 6 /μl (SD-0.41), 26.6 pg (SD-2.5) and 31.88(SD-0.93), respectively.Haemoglobin was distributed between 7.4 to 19.6 g/dl, and the mean was 11.9 g/dl (SD 1.0). Mean MCV was 83.2 fl (SD 6.4). Mean RCC, MCH and MCHC were 4.51*10n = 451). None of them had severe anaemia (Hb < 7 g/dl), and the majority  had mild anaemia. A haemoglobin level of 13 g/dl or more was observed in 399 (12.7%). The types and severity of anaemia in the sample is shown in Fig. The prevalence of anaemia in the study sample was 14.4% . The mean haemoglobin level in the group with microcytic anaemia and normal RCC was 9.9 g/dl (SE-0.1).Microcytic red cells were seen among 638 (20.4%) of the participants. The majority of anaemic women  had microcytic anaemia. Of them, 91 had RCC more than 5 * 10Normocytic normochromic anaemia was seen among 114 25.3%) anaemic women. Their mean haemoglobin level was 10.6 g/dl. Normocytic hypochromic anaemia was seen in 80 (17.8%) anaemic women who had mean haemoglobin of 10.5 g/dl. Two (0.4%) of the anaemic women had macrocytic anaemia (mean haemoglobin level 9.6 g/dl). Distribution of Haemoglobin and Red cell indices; RCC, MCV, MCH, MCHC according to the type of anaemia is presented in Fig. 5.3% anaeA small random subsample of 11 out of the 163 of them underwent peripheral blood film analysis. Minor hemoglobinopathy was seen in four, iron deficiency and early iron deficiency were seen in three each, and early megaloblastic changes were seen in one participant(s). HPLC reports were available in 21 , and 14 of them were confirmed as having thalassemia trait.A blood film reporting was available for 89 out of 114 women with normocytic normochromic anaemia . Four cases  of South-East Asian Ovalocytosis were detected. It contributed to 0.9% (95% CI 0.3 to 2.3%) of anaemia in first trimester women.Features of iron deficiency, early mixed deficiency, mixed deficiency, early megaloblastic changes and megaloblastic changes were observed in 38 (40.9%), 18 (19.4%), 6 (6.5%), 7 (7.5%) and 1 (1.1%), respectively. 19 (20.4%) blood film reports were normal. Two pregnant women, the one with megaloblastic changes and another with early megaloblastic features in their blood films, were tested for B12 and folate deficiencies. Both were confirmed as having B12 deficiency. None of them had folate deficiency.Blood films were reported in 24 out of the 91 with microcytic anaemia and high RCC. As hypothesised, all 24 had features of minor hemoglobinopathy. Independently of them, 19 underwent HPLC as a part of this study and 17 had undergone HPLC previously. Beta Thalassemia trait was diagnosed in 35 of them while the other had Haemoglobin SE disease (HbSE). Thus, with a 100% positive predictive value observed , we estimated that all 91 participants with microcytic anaemia and high RCC had minor hemoglobinopathies.Seven randomly selected participants (out of the 84) underwent peripheral blood film analysis. Four were having changes suggestive of early iron deficiency. Two had normal blood film reporting, and one had megaloblastic changes. Independent to this, five had records of past HPLC testing, and all five were negative for minor hemoglobinopathies.Only one out of the two cases of macrocytic anaemia had a peripheral blood film reporting. The blood film showed early megaloblastic changes. However, her serum B12 level was 321 pg/ml, and her serum folate level was 29.2 ng/ml.Peripheral blood film was analysed in a random sample of 143 non-anaemic women. Minor hemoglobinopathy, early iron deficiency and iron deficiency was suggested in 7 (4.9%), 12 (8.4%) and 2 (1.4%) of the blood films, respectively, and the others  did not show an abnormality.Of the 2676 non-anaemic women, 145 had HPLC reports , and 12 of them were confirmed to have minor hemoglobinopathies.213 random first trimester pregnant women from the total sample were selected for sub-sample analysis for serum ferritin. Anaemia prevalence in this sub-sample was 14.5% (n-31).The distribution of serum ferritin was skewed to the right (skewedness 2.78). The mean and median serum ferritin level among 213 first trimester women was 67.6 (SD 55.5) and 56.8. Iron deficiency (serum ferritin < 30 ng/ml) was seen in 20.2% . Serum ferritin was less than 15 ng/ml in nine (4.2%) participants. Respectively, 164 (77%) and 6 (2.8%) of participants had s. ferritin between 30 to 199.9 ng/ml and ≥ 200 ng/ml. Of those with iron deficiency, 13 (30.2%) had anaemia, while 30 (69.8%) were non-anaemic. Conversely, 41.9% of anaemic and 15.7% of and non-anaemic participants were iron deficient.Serum ferritin level and red cell indices-based evidence on possible iron deficiency shows poor agreement Table . FerritiOf these 31 anaemic pregnant women, 21 came for serum vitamin B12 and folate testing. Both parameters had wide variation among the participants.Serum Folate levels ranged between 5 and 14 ng/ml. Median, Mean and SD were 14 g/ml, 19 ng/ml and 10, respectively. Folate deficiency (< 4 ng/ml) was not observed among participants. However, one (4.8%) had a folate level below 5.9 ng/ml (risk of deficiency), and eight (38%) had high folate levels above 20 ng/ml.Serum Vitamin B12 level of the sample varied between 154 and 721 (pg/ml). The Median was 301 pg/ml, mean was 359 pg/ml (SD178). B12 deficiency (B12 < 203 pg/ml) was observed among 5 (23.8% CI 10.6–45.1). Another five had B12 levels between 203 to 300 pg/ml, while 11 (52.4%) had B12 levels more than 300 pg/ml.None of those with B12 deficiency had Macrocytic anaemia (according to red cell indices). However, the peripheral blood film of one of them showed oval Macrocytes. Co-existing iron deficiency was seen in two. Three of the five had high folate levels. The distribution of B12, folate and ferritin levels and types of anaemia are shown in Fig. n = 9, 2.1%), liver , renal , or autoimmune diseases . Fissure’s exact test showed that prevalence of anaemia was not significantly different between groups with and without a diagnosed thyroid (p – 0.87), liver (p − 0.06), renal (p-1) or autoimmune disease (p-0.21).Small percentages of anaemic pregnant women had previously diagnosed thyroid (n = 105) of first trimester anaemic women have minor hemoglobinopathies. The prevalence of iron deficiency, B12 deficiency and Southeast Asian ovalocytosis were estimated as 41.9% (95% CI 26.4–59.2), 23.8% (CI 10.6–45.1), and 0.9 95% CI 0.3 to 2.3%) of first trimester anaemic women respectively. Folate deficiency was not observed among them.In summary, we estimated that at least 23.3%  and very high iron deficiency prevalence (69% with 12 ng/dl cut off) during pregnancy . ProbablEven though the ferritin levels suggest a comparatively low prevalence of iron deficiency, the majority of the participants have microcytic anaemia (35.9% when high RCC is excluded) and normocytic hypochromic anaemia (18.4%). These indicators are usually attributed to iron deficiency . PreviouTwo previous studies conducted in more urban settings in Sri Lanka; among school dropped out girls (15 to 19 years old) and nonpregnant, nonlactating females (15 to 30 years old), have shown a low prevalence of B12 deficiency (1.6 and 0.44% respectively) , 63. To B12 deficiency during pregnancy is associated with low birth weight, preterm delivery and neural tube defects in addition to maternal anaemia , 70. The. It is noteworthy that a significant proportion, including 60% of the B12 deficient participants, had high folate levels. Since evidence suggests that high folic acid levels may exaggerate the effects of B12 deficiency, it is worthwhile to reconsider the strategy of supplementing high doses of folic acid  without B12 supplementation [Folic acid deficiency has been reported among reproductive-age females of the country , 63. Howentation , 71.Folate or B12 deficiency is expected to cause macrocytic anaemia . StudiesSouth-East Asian Ovalocytosis has been reported from Sri Lanka previously. This is the first study reporting the significance of south-east Asian ovalocytosis in Sri Lankan pregnant women , 74. OneWe did not find evidence suggesting thyroid, liver, renal or autoimmune diseases significantly contributing to maternal anaemia in this community, perhaps due to the low number of reported cases. Even though Malaria and HIV contribute to significant numbers of anaemia in pregnant women around the globe, we did not test for them in the current study as the prevalence of both conditions in Sri Lanka are negligible , 76.This study has several limitations. Some aetiologies were assessed based on an evidence-based algorithm instead of a universal screening due to funding restrictions. Further, the prevalence of alfa thalassemia was not covered in this study. We established that B12 deficiency is prevalent in this community, but the sample tested was small, and studies with a larger sample are required to obtain proper estimates. Such assessments should include other micronutrient deficiencies such as vitamin B6 and Zinc as well.The findings of this study from rural Sri Lanka calls for a re-evaluation of current universal strategies implemented in preventing anaemia in pregnancy. Even in low- and middle-income settings where iron deficiency is prominent, and the first line of management is doubling the iron dose, exploring the underlying causes of maternal anaemia will help improve mothers and babies health.We have shown that iron deficiency remains a major cause of anaemia in pregnant women despite already implemented preventive strategies across the lifecycle. Bio-socio-cultural reasons for the continued predominance of iron deficiency in this community need to be evaluated further. Minor hemoglobinopathies significantly contribute to anaemia in pregnancy. The role of minor hemoglobinopathies in maternal anaemia in other LMIC’s needs to be further investigated. Application of sound evidence on aetiologies of anaemia in pregnancy will be beneficial in reviewing current policies and strategies in LMICs for further improvement of health in mothers and babies.


Triple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers and is associated with younger age at diagnosis, greater recurrence risk and shorter survival time. Therapeutic options are very scarce. Aim of the present analysis is to provide further insights into the clinical activity of metronomic chemotherapy (mCHT), in a real-life setting.We used data included in the VICTOR-6 study for the present analysis. VICTOR-6 is an Italian multicentre retrospective cohort study, which collected data of metastatic breast cancer (MBC) patients who have received mCHT between 2011 and 2016. Amongst the 584 patients included in the study, 97 were triple negative. In 40.2% of the TNBC patients, mCHT was the first chemotherapy treatment, whereas 32.9% had received 2 or more lines of treatment for the metastatic disease. 45.4% out of 97 TNBC patients received a vinorelbine (VRL)-based regimen, which resulted in the most used type of mCHT, followed by cyclophosphamide (CTX)-based regimens (30.9%) and capecitabine (CAPE)-based combinations (22.7%).Overall response rate (ORR) and disease control rate (DCR) were 17.5% and 64.9%, respectively. Median progression free survival (PFS) and overall survival (OS) were 6.0 months (95% CI: 4.9–7.2) and 12.1 months (95% CI: 9.6–16.7). Median PFS was 6.9 months for CAPE-based regimens (95% CI: 5.0–18.4), 6.1 months (95% CI: 4.0–8.9) for CTX-based and 5.3 months (95% CI: 4.1–9.5) for VRL-based ones. Median OS was 18.2 months (95% CI: 9.1-NE) for CAPE-based regimens and 11.8 months for VRL- (95% CI: 9.3–16.7 and CTX-based ones (95%CI: 8.7–52.8). Tumour response, PFS and OS decreased proportionally in later lines.This analysis represents the largest series of TNBC patients treated with mCHT in a real-life setting and provides further insights into the advantages of using this strategy even in this poor prognosis subpopulation. Triple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers and is associated with younger age at diagnosis, greater recurrence risk and shorter survival time . Due to In this context, metronomic chemotherapy (mCHT) may represent a promising therapeutic strategy in the metastatic setting: it refers to the repeated administration of low doses of a chemotherapy agent to maintain prolonged and active plasma concentrations and to provide a favourable toxicity profile . It is pIn vitro studies showed that mCHT inhibits the formation of new vessels through the induction of anti-angiogenic factors, like thrombospondin-1 , and to Clinical studies in advanced breast cancer patients, evaluating the metronomic administration of one or more agents are encouraging, showed a response rate around 30–44% and a clinical benefit rate of approximately 70% –11. VICTWe identified all the TNBC cases enrolled into the VICTOR-6 study, as planned for this pre-specified analysis.The main study  obtainedEligibility criteria and treatment plan have been described in the main paper.All measures of clinical outcomes were based on the physician’s evaluation. Primary endpoint of this analysis is to describe the clinical activity of mCHT in terms of ORR and DCR; PFS, OS, safety are secondary endpoints, as in the main paper. Patients who had not progressed, or had died were censored at the data cut-off date .Demographic data, patients’ baseline characteristics and disease, plus treatment information were summarized with standard summary statistics . Relationships of these variables with response were analysed by mead of a Mantel–Haenzel. Time to event analysis was described by Kaplan–Meier approach and association with baseline characteristic was analysed by stratified log-rank test and proportional hazard model.Univariate and multivariate logistic analyses were used for estimating the association of selected basal characteristics and treatment with response. Odds ratio and relative 95% confidence interval (CI) were used as summary statistics. The number of patients was calculated in order to obtain a quite precise description of chosen statistics and a good fit with the Cox model.The data were statistically analysed using SAS version 8 .Between January 2011 and December 2016, we retrospectively retrieved clinical data of 584 metastatic breast cancer patients treated with mCHT, of whom 97 (16.6%) patients were classified TNBC, according to ASCO-CAP guidelines , who areAt primary diagnosis, main tumour characteristics were ductal histology (88.2%), pT2 stage (53.6%), pN1 stage (31.9%); 21 (21.6%) patients were metastatic at diagnosis. Grading was G3 in 66% of the tumours.Median follow-up time was 37.6 months (13.3–41.8). Median age at the time of diagnosis was 67 years (30–88). Median Disease Free Interval (DFI) was 17 months (0–288).At the time of first relapse, 41.2% of the patients had 2 or more metastatic sites; bone was the main site involved , but brain metastases were present in 5.2% of the patients.At the beginning of mCHT, the median age of the patients was 68 years (30–88), most of them had an ECOG PS of 0 (53.6%) or 1 (32.9%). Almost half of the patients had 2 or more metastatic sites (45.4%); main sites of metastases were bone (41.2%) and lung (38.1%). Central Nervous System (CNS) involvement was present in 10.3% of the patients. Table In 40.2% of the patients, mCHT was the first chemotherapy treatment, whereas 32.9% had received 2 or more lines of treatment for the metastatic disease.Forty-four (45.4%) out of 97 TNBC patients received a VRL-based regimen, which resulted in the most used type of mCHT, followed by CTX-based regimens  and CAPE-based combinations . MTX-based regimens were only occasionally used (1 patient).Most of the patients received mCHT as single-agent ; 40.2% of the patients have been treated with mCHT in first-line setting . Table Regarding clinical activity, Overall Response Rate (ORR) and DCR were 17.5 and 64.9%, respectively. Best ORRs and DCRs were observed in first-line settings (20.9 and 76.7%), whereas tumour response decreased proportionally in later lines . Table In TNBC patients, both ORRs and DCRs resulted in lower percentages in comparison to those obtained in Luminal patients enrolled into the main study , independently of the line of treatment. Table Median PFS and OS were 6.01 months (95% CI: 4.9–7.2) and 12.1 months (95% CI: 9.6–16.7) in the whole TNBC population, respectively.Median PFS was 6.9 months for CAPE-based regimens (95% CI: 5.0–18.4), 6.1 months (95% CI: 4.0–8.9) for CTX-based and 5.3 months (95% CI: 4.1–9.5) for VRL-based ones  vs 6.3 months (95% CI: 4.1–13.2) and 3.0 months (95% CI: 1.7-NE) for second and subsequent lines  for CAPE-based regimens and 11.8 months for VRL- (95% CI: 9.3–16.7 and CTX-based ones (95% CI: 8.7–52.8)  vs 13.7 months (95% CI: 9.0-NE) for first- and second-line treatment, respectively , followed by nausea and vomiting and diarrhoea  and fatigue (10.3%). Grade 3–4 haematological toxicity, mainly neutropenia, was reported in 8.2% of the cases and Grade 3–4 liver toxicity in 3.1% of the patients.Table The analysis presented in this paper explores the role of mCHT in advanced TNBC in a real-life setting as part of the VICTOR-6 study, an observational, retrospective study regarding the use of mCHT in the strategy of treatment of advanced breast cancer patients .Median DFI in our TNBC population was 17 months (0–288), lower than that observed in the Luminal counterpart, but aligned to what reported in different studies for this subset of patients.TNBCs are definitely biologically aggressive; shortened disease-free intervals in the adjuvant and neoadjuvant setting and a more aggressive clinical course in the metastatic setting remain the main factors contributing to this worse outcome , 15. In Even though mCHT is considered by many oncologists to be a palliative treatment, 40.2% of the patients included in the present analysis received this treatment as first-line therapy, in comparison to 72 out of 487 (14.8%) Luminal BC population. Considering that the median age is approximately the same and the distribution of metastases is very similar between TNBC and Luminal BC in our collection, this finding could deserve further insights, also considering that, in the TNBC group, mCHT was used mainly as monotherapy .We can argue that most oncologists consider the prognosis of these patients so desperate that they set up a therapy with purely palliative purposes from the beginning, despite international guidelines suggesting using doublets or triplets .Metronomic VRL-based regimens were found to be the most used in TNBC patients (45.4%) as in Luminal BC ones (53.6%), whereas CTX-based regimens were found to be used in a higher percentage (30.9%) in TNBC patients, in comparison to Luminal ones (19.7%). Even if the small number of patients could have affected this finding, we can hypothesize that different pre-clinical results reporting the immune modulatory activity of CTX , 18, as No data are available on PDL-1 and Tumour infiltrating lymphocytes (TILs) levels in VICTOR-6 TNBC patients, as these tests were not yet routinely performed during the study period. However, taking into account the growing evidence of the immune modulatory activity of mCHT and the current possibility of using immunotherapy in TNBC, these analyses deserve further investigation in future studies.ORR and DCR were 17.5 and 64.9%, respectively and best ORRs and DCRs were observed in first-line settings (20.9 and 76.7%). These rates are lower than those observed in Luminal tumours, being 29.5 and 76.4%, respectively . Median PFS and OS were 6.01 months (95% CI: 4.9–7.2) and 12.1 months (95%CI: 9.6–16.7), respectively.Main reason for discontinuation was disease progression in the TNBC group (68%), as in Luminal patients (71.5%).It is quite common to observe a lower activity of the same drugs or regimens in TNBC patients in comparison to their Luminal counterpart, even with standard chemotherapy: i.e. for paclitaxel, ORR ranged from 20.0 to 28.6% according to the different studies  in TNBC,Other Authors  reportedDespite the relative variety of regimens included in the present analysis, clinical activity of mCHT in this real-life setting is very close to the one observed in prospective clinical trials , 22.In the VICTOR-6 study, the analysis of the TNBC patient’s subgroup  showed tYoshimoto et al.  treated  and in vivo studies suggest that mCHT can exert a role in the control of both TNBC cell lines and mouse models [Our outcomes are supported and can be explained by emerging preclinical data. Indeed, in vitroe models , 23, 24.Very recently, Espanol et al.  investigDi Desidero et al.  studied Finally, our group reported that the metronomic combination of VRL and 5-Fluorouracil is able to significantly induce cell death by promoting apoptosis and/or autophagy in TNBC cell lines .To our knowledge, this is the largest series of TNBC patients treated with mCHT in a real-life setting. Considering that it has become more and more difficult to conduct studies in this setting of patients, mainly due to the high competitiveness of more recent targeted drugs, we strongly believe that our data can provide further insights of the real value of this strategy even in this poor prognosis subpopulation. This should be of great importance especially for TNBC patients in disadvantaged parts of the world such as LMICs, where most of the new drugs are not available for all patients.


As the voiding habits of Iranian children differs from other children because of some cultural and religious considerations, we aimed to establish normal reference values of urinary flow rates in Iranian children between 7 to 14 years of age.Eight hundred and two uroflowmetry studies were performed on children with no history of a renal, urological, psychological or neurological disorder, between the ages 7 and 14. Five hundred twenty five studies from 192 girls and 335 boys were considered in this study excluding the staccato/interrupted voiding pattern or voided volume less than 20 ml. The voiding volume, the maximum and average urinary flow rates were extensively analyzed.The maximal and average urine flow rate nomograms were plotted for both girls and boys. Mean maximum urine flow rate was 19.9 (ml/sec) for boys and 23.5 (ml/sec) for girls with a mean voided volume of 142 (ml) for boys and 147 (ml) for girls. Flow rates showed a close association with voiding volume in both sexes. The maximum and average flow rates were higher in girls than in boys, and they showed a significant increase in flow rates with increasing age, where boys did not. The mean maximum urine flow rates (19.9 ml/sec for boys and 23.5 ml/sec for girls) were found to be higher in this study than other studies.Nomograms of maximal and average flow rates of girls and boys are presented in centile form, which can help the physician to evaluate the response to medical or surgical treatment and be useful for the screening of lower urinary tract disturbances in children, for a wide range of voided volumes. Uroflowmetry is the most commonly used form of urodynamic testing. Simply stated, Uroflowmetry is the measurement of the rate of urine flow over time. It is easy to perform and it is a non-invasive test. Uroflowmetry alone is rarely able to determine the cause of a voiding dysfunction; however, it is extremely useful in selecting patients for more complex urodynamic testing . It alsoScott and Mcllhaney  measuredSiroky et al.  construcThis cross-sectional study was performed from April 2000 to February 2001 among 7–14 years old children. The study was approved by the Institutional Board Review and the Medical Ethics Committee of Tehran University of Medical Sciences. The samplings were done in 15 different schools throughout the city of Tehran.We had many discussion sessions for children's parents as well as their teachers and other school staff, explaining the program and its harmlessness for the children. Children who wanted to take part in the program voluntarily and their parents filled in an informed consent were entered in this study.Participants (n = 802) were told by their teacher to come to school with a full bladder in the morning. The mictiograph consisted of an electronic transducer installed in a specific toilet, with the recording equipment in a separate place. Testing was performed in a completely private toilet, lockable from inside. A nurse, skilled in clinical pediatric urology, helped us with the sampling, especially in girls' schools. Children started voiding when the operator told them. All children voided at maximum sensation of bladder fullness. No positional restriction during testing was applied and children were told to void in their habitual positions rather than specifying them to sit or stand. Uroflowmetry was performed using a uroflowmeter model Micromedics System/H, Model no. DPU- 441, Type 1001H 1995, England.Uroflowmetry was performed on 802 children with no history of renal, urological, psychological or neurological disorder, 275 of the studies were excluded from the study because their voided volumes were less than 20 ml  or theirP value of 0.05 or less was considered as statistically significant. Several transformations of data were assessed and the goodness-of-fit tested to determine whether a linear, hyperbolic, parabolic or logarithmic function best described the relation between the maximum or average flow rates and the voided volume [t-test.Statistical analysis was performed using SPSS software for Windows version 11. A d volume . The quiWe included Uroflowmetry studies of 527 children, 335 boys (63.6%) and 192 girls (36.4%) 7 to 14 years old. The mean age was 10.44 ± 2.25 years for boys and 9.73 ± 2.17 for girls.The mean voided volumes were 142 ± 97.5 ml in boys and 147 ± 89.74 ml in girls. The mean maximum flow rate was 19.95 ± 10 (ml/sec) in boys and 23.52 ± 8.7 (ml/sec) in girls. The mean average urine flow rates were 8.1 ± 4.4 (ml/sec) for boys and 8.8 ± 4.2 (ml/sec) for girls. The minimum acceptable flow rates for boys and girls regarding age are shown in Table P = 0.099 for Q-max and 0.09, P = 0.835 for Q-ave) but showed a statistically significant increase with age in girls . So, in our study girls showed statistically significant increases in urine flow rates with age but boys did not. This increase was approximately 0.92 (ml/sec/year) for maximum urine flow rate and 0.51 (ml/sec/year) for average urine flow rate in girls between the ages 7 and 14.Maximum and average flow rates showed no significant increase with age in boys  Square root (Q-max) = 2.05 + 0.2 × Square root (VV)0: slope = 0, P < 0.001)Root mean square error = 0.44 (H(b) Square root (Q-ave) = 1.36 + 0.12 × Square root (VV)0: slope = 0, P < 0.001)Root mean square error = 0.38  Ln (Q-max) = 1.06 + 0.42 × Ln (VV)0: slope = 0, P < 0.001)Root mean square error = 0.36 (H(b) Square root (Q-ave) = - 0.67 + 0.74 × Ln(VV)0: slope = 0, P < 0.001)Root mean square error = 0.39  in men or 15 (ml/s) in women might fall just inside the fifth centile curve at 200 (ml) voided volume, although well outside the same curve at 400 (ml). The normality of these flow rates may then be interpreted quite differently at these 2 voiding volumes.Siroky and colleagues were among the first to develop a nomogram that allowed uroflow to be corrected for voided volume. They also applied their nomogram to evaluation of men with bladder outlet obstruction. The authors stated that Q-max was a more sensitive indicator of outlet obstruction than Q-ave .The Liverpool  nomogramThe use of statistical transformation by Gierup  and JensAbele and Krepler  reportedThe mean maximum and average urine flow rates found higher in girls than in boys. This is interpretable by the girl's shorter urethra. The mean maximum urine flow rates (19.9 ml/sec for boys and 23.5 ml/sec for girls) were found to be lower in this study than those reported in western studies  declare that they have no competing interests.AMK conceived the study, participated in its design and coordination and finalized the manuscript. CAY and OR participated in design, collected the necessary data, reviewed the literature, and wrote a first draft of the manuscript. PT have reviewed the literature, edited the draft, revised the statistical analyses and nomograms and submitted the manuscript. PM participated in the design of the study. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


The influence of a new aromatase inhibitor, CGS 16949A on peripheral aromatisation of androstenedione into oestrone was investigated in postmenopausal women with breast cancer. A mixture of 3H androstenedione and 14C oestrone was injected, and all urine was collected for the following 96 h. The isotope ratio was determined in the urinary oestrogen metabolites after isolation by HPLC. Eight patients were investigated before and during treatment with CGS 16949A. At a dose of 1 mg b.d. (eight patients) CGS 16949A inhibited aromatisation by a mean value of 82.4% (range 71.3 to 93.7%). When the drug dose was escalated to 2 mg b.d. (three patients) aromatisation was inhibited by a mean of 92.6% (range 90.6 to 95.8%), these results suggest that CGS 16949A at a dose of 1 mg b.d. causes submaximal aromatase inhibition in many patients, while a dose of 2 mg b.d. seems to result in greater than 90% aromatase inhibition. These data are consistent with previous observations that the higher dose is more effective in suppression of plasma oestradiol levels.