4-Hydroxybutyric Aciduria as a Rare Presentation of Global Developmental Delay in Children: Case Report of Two Different Patients

Succinic semialdehyde dehydrogenase (SSADH) deficiency or 4-Hydroxybutyric Aciduria is an autosomal recessive inherited disorder of amma-aminobutyric acid (GABA) degradation. It is characterized by developmental delay, infantile-onset hypotonia, cognitive impairment language deficit, and ataxia. Epilepsy, aggression, Hyperkinetic behavior, hallucinations, and sleep disturbances have been described in about half of the patients, more frequently in older individuals. Its management is largely symptomatic, conducted at the treatment of seizures and neurobehavioral disorder. We present two girls with chief complaint of hypotonia and developmental delay how referred to department of Pediatrics (Ghaem hospital), Mashhad, Iran

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Lingual Thyroid: A Case Report and Literature Review

Thyroid ectopia is a dysgenesis of thyroid gland and Lingual position represents the most frequent ectopic location accounting up to 90% of ectopic cases. Hypothyroidism is commonly present because of absence of a normal thyroid gland in most instances. Primary hypothyroidism in juvenile population generally leads to retardation of linear growth and delay or even arrested puberty. We present a 20 years old female with typical and profound presentation of hypothyroidism due to lingual thyroid

Ultrasonographic Changes of the Uterus and Ovaries in Female Infants with Congenital Adrenal Hyperplasia: Pseudo-Testicular Sign

Background: Congenital Adrenal Hyperplasia (CAH) is one of the main causes of ambiguous genitalia. The unusual appearance of internal genitalia in CAH patients is similar to many other conditions which are classified in Disorders of Sex Development (DSD). This study aimed to accurately describe diagnostic ultrasonic features of the uterus and ovaries in CAH patients in order to distinguish it from other causes of ambiguous genitalia. Methods: This cross-sectional study was performed in Akbar Children Hospital, Mashhad University of Medical Sciences, Mashhad, Iran, from 2017 to 2020. Ultrasound findings of the uterus and ovaries of 22 female infants (2-60 days of age) with CAH due to 21-hydroxylase deficiency and 47 healthy infants with a similar age were recorded and eventually analyzed in this study. Results: All the healthy infants in the control group had a normal prominent cervix, except for two neonates (95%). In the case group, only 9 (41%) infants had a normal prominent cervix, and other 13 newborns had nearly equal sizes of fundus and cervix. There was a significant difference between the two groups in the fundus-to-cervix ratio (P=0.009). The 77% patients had no follicles in both ovaries, while 28% healthy infants in the control group had no follicles, and the rest had unilateral or bilateral multi-follicular ovaries. After two months following treatment, bilateral multi-follicular ovaries were observed in all patients. The sign of non-follicular ovaries (pseudo-testicular appearance) was significantly more prevalent in the case group (P=0.004). Furthermore, half of infants showed normal pelvic lymph node that mimic a testicular-like appearance due to its uniform hyper-echoic texture. Conclusion: The testicular-like appearance of normal pelvic lymph nodes and non-follicular ovaries in a female infant with CAH. Attention to these usual findings can prevent misdiagnoses of cryptorchidism and time loss to perform other laboratory tests and karyotyping

A Ten-Year Study on the Prevalence and Frequency of Risk Factors for Breast Cancer in Sabzevar, Iran

Background & aim: Evaluation of prevalence of risk factors for breast cancer in different regions of Iran and identification of their significant effect on this disease can promote the prevention and reduction of breast cancer incidence. Therefore, this study aimed to evaluate the prevalence, demographic characteristics, and frequency of the risk factors of breast cancer during 10 years. Methods:This cross-sectional study was conducted on 160 women with breast cancer during 10 years. The samples, referred by health connectors and registration centers for patients with cancer, were selected using census sampling. Research tool was a reliable and valid researcher-made questionnaire, validity and reliability of which were confirmed. Data analysis was performed in SPSS version 16 using descriptive statistics. Results: In total, mean age of surviving women was 50.7±1.2 years. The highest incidence rate of breast cancer was 35.2% in the group of participants aged 40-49, while the highest prevalence rate of this disease was 0.432 per 1000 samples in a group of patients aged 50- 59 years. Moreover, the most frequent risk factors for this disease were previous use of oral contraceptive pills (OCP) (56.8%) and positive family history (19%). Conclusion: The results of this study were indicative of positive family history as a certain risk factor for breast cancer in Sabzevar. Therefore, it is recommended that special attention be paid to women with positive family history of breast cancer. Therefore, prioritization of breast cancer screening and prevention programs is of paramount importance in this regard

The prevalence of clarithromycin-resistant Helicobacter pylori isolates: a systematic review and meta-analysis

Background Knowledge of global clarithromycin (CLA)-resistant rates of Helicobacter pylori (H. pylori) is crucial for decision of the most appropriate eradication therapies with good clinical outcomes. Therefore, this review and meta-analysis aimed to evaluate the global prevalence of the CLA resistance in H. pylori to provide some guidance for selecting the first-line antibiotics. Method A comprehensive search was performed for relevant literature until April 2021 in PubMed, Embase, and Web of Science databases. Freeman-Tukey double arcsine transformation was performed to estimate the weighted pooled prevalence of resistance. Results The meta-analysis included 248 articles. The prevalence of CLA-resistant H. pylori was 27.53% (95% CI [25.41–29.69]). The heterogeneity between reports was significant (I2 = 97.80%, P 0.05). Conclusion Overall CLA resistance rate was 27.53%, worldwide. The difference in CLA resistance rate among the included studies can be due to several reasons such as differences in antibiotic prescription rates in various geographic areas, use of different breakpoints or inaccurate criteria in performed studies, and the emergence of multidrug-resistant (MDR) strains

Successful IgM-enriched immunoglobulin treatment in severe COVID-19 pneumonia: a case report

Coronavirus disease (COVID-19) pandemic has turned into one of the most considerable challenges worldwide. The optimal treatment strategy, particularly in severely ill patients, is still unrecognized. IgM-enriched immunoglobulin (Pentaglobin®, Biotest AG, Dreieich, Germany) contains IgM, IgA and IgG against a variety of pathogens representing passive immune protection for affected individuals and it may be effective in the treatment of COVID-19. On March 16, 2020, a 32-year-old woman presented to Masih Daneshvari Hospital, Tehran, Iran. On admission, the peripheral oxygen saturation (O2 Sat) was 84%. Spiral chest computed tomography (CT) scan revealed bilateral ground-glass opacification (GGO) involvement. On March 19, 2020, the clinical condition was deteriorated, and her O2 Sat decreased to 70% in ambient air. Treatment with IgM-enriched immunoglobulin was immediately initiated over the course of three days (total dose for the patient was calculated to be 1500 ml). On the seventh day of hospitalization, the patient was discharged with satisfactory general condition, without any complaints, and with stable vital signs and O2 Sat of 95% on room air. In conclusion, IgM-enriched immunoglobulin could be considered as a potential option for the treatment of severely ill patients with COVID-19