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A proposal for developing a large patient population cohort for longterm safety monitoring in rheumatoid arthritis. OMERACT Drug Safety Working Party.

This paper proposes the creation of an objectively acquired reference database to more accurately characterize the incidence and longterm risk of relatively infrequent, but serious, adverse events. Such a database would be maintained longitudinally to provide for ongoing comparison with new rheumatologic drug safety databases collecting the occurrences and treatments of rare events. We propose the establishment of product-specific registries to prospectively follow a cohort of patients with rheumatoid arthritis (RA) who receive newly approved therapies. In addition, a database is required of a much larger cohort of RA patients treated with multiple second line agents of sufficient size to enable case-controlled determinations of the relative incidence of rare but serious events in the treated (registry) versus the larger disease population. The number of patients necessary for agent-specific registries and a larger patient population adequate to supply a matched case-control cohort will depend upon estimates of the detectability of an increased incidence over background. We suggest a system to carry out this proposal that will involve an umbrella organization, responsible for establishment of this large patient cohort, envisioned to be drawn from around the world.

Adverse Drug Reaction Reporting Systems↗

Difference in bone acquisition among hormonally treated postmenopausal women with normal and low bone mass.

This prospective analysis was conducted to compare the effects of hormone treatments on bone mineral density (BMD) of the lumbar spine, hip, and distal forearm in postmenopausal women with normal BMD and those with low bone mass. Eighty healthy women were randomly assigned to receive a cyclic regimen of standard hormone replacement therapy (HRT) or currently used low-dose oral contraceptive (OC). Women were categorized as normal BMD and low bone mass according to the Thai reference database. The results revealed that women with low bone mass gained more BMD than those with normal BMD. The difference in mean per cent bone acquisition was obvious at the spine. In addition, further subset analysis into OC and HRT groups revealed higher effects of OC on BMD when compared to HRT.

Adult↗

Quality assurance of autopsy face sheet reporting, final autopsy report turnaround time, and autopsy rates: a College of American Pathologists Q-Probes study of 10003 autopsies from 418 institutions.

OBJECTIVE: To develop a multi-institutional reference database of autopsy practice and performance for quality improvement purposes. DESIGN: In 1990, participants in the Q-Probes quality improvement program of the College of American Pathologists (CAP) each retrospectively evaluated the 25 most recently completed consecutive autopsy reports and determined the number of deaths and autopsies that occurred in their institutions during 1989. SETTING: Hospital-based autopsies excluding forensic cases and stillborn infants. PARTICIPANTS: Four hundred ten institutions in the United States and eight institutions in Canada. MAIN OUTCOME MEASURES: Completeness of face sheet information contained in final autopsy reports, turnaround time for completion of final reports, and institutional autopsy rates. RESULTS: In the aggregate database of 10003 autopsies, the following six data items (from a total of 21) were present in 95% to 100% of the final autopsy reports in at least 85% of the participating institutions: institution where autopsy was performed, patient's name, patient's sex, autopsy number, autopsy date, and prosecter's name. The turnaround times for the final autopsy reports were as follows: 30 days or less in 47.6% of the cases, 31 to 60 days in 28.8%, and more than 60 days in 23.7%. A higher median percentage of autopsy final reports were completed in 30 days or less in institutions with the following characteristics: nonteaching (P < .004), no pathology residency program (P < .002), and rural location (P < .027). A lower number of autopsies performed in 1989 was associated with a higher median percentage of final reports completed in 30 days or less (P < .007). The aggregate autopsy rate for all participating institutions was 12.4%, and the median rate was 8.3%. Median autopsy rates for teaching institutions and institutions with pathology residency training programs were 15% and 19%, respectively. CONCLUSIONS: This multi-institutional study identified a core group of face sheet data items that were consistently present on final autopsy reports. However, the majority of the face sheet data items examined were inconsistently recorded. Approximately 75% of final autopsy report turnaround times were within the standard established by the Joint Commission on Accreditation of Healthcare Organizations. Nearly two thirds of the institutions reported autopsy rates for 1989 of 0% to 10%.

Autopsy↗

Extraneous tissue in surgical pathology: a College of American Pathologists Q-Probes study of 275 laboratories.

OBJECTIVE: To develop a multi-institutional reference database of extraneous tissue (contaminants) in surgical pathology. DESIGN: In 1994, participants in the College of American Pathologists Q-Probes quality improvement program performed prospective and retrospective evaluations of extraneous tissue found in surgical pathology microscopic sections for a period of 4 weeks or until 1000 slides were reviewed in each participating laboratory. PARTICIPANTS: Two hundred seventy-five surgical pathology laboratories institutions, predominantly from North America. MAIN OUTCOME MEASURES: Extraneous tissue contamination rate for slides in prospective and retrospective reviews; staffing and practice procedures; location of extraneous tissue on slides; type of extraneous tissue (normal, abnormal, nonneoplastic, neoplasm, microorganisms, etc); class of extraneous tissue (slide or block contaminants); source of extraneous tissue (different or same case); origin of extraneous tissue (pathology laboratory, physician's office or operating room); and degree of diagnostic difficulty caused by extraneous tissue. RESULTS: Three hundred twenty-one thousand seven hundred fifty-seven slides were reviewed in the prospective study and 57083 slides in the retrospective study. There was an overall extraneous tissue rate of 0.6% of slides (2074/321757) in the prospective study and 2.9% of slides (1653/57083) in the retrospective study. Of those slides with extraneous tissue, the extraneous tissue was located near diagnostic tissue sections in 59.5% of the slides reviewed prospectively and in 25.3% of slides reviewed retrospectively; deeper sections were performed to evaluate extraneous tissue in 12.2% of prospective cases and in 3.1% of retrospective cases. Of the laboratories, 98% had written guidelines for changing solution in tissue processors, and 64.9% had guidelines for maintaining water baths free of extraneous tissue. A total of 98.9% used lens paper, filter bags, or sponges for processing fragmented and small specimens. Written protocols for documentation of extraneous tissue in surgical pathology reports were established in 6.1% of laboratories, for removal of extraneous tissue from blocks in 5.7%, and for removal of extraneous tissue from microscopic slides in 4.7%. In 24% of laboratories no comment or record was kept to document extraneous tissue. Extraneous tissue consisted of neoplasm in 12.7% of the prospectively reviewed slides and in 6.0% of the retrospectively reviewed slides. For the prospective study, 59.4% of extraneous tissue was classified as slide contaminants, and 28.4% was found to be contaminants within the paraffin block; for the retrospective study, 72.9% was classified as slide contaminants and 15.9% as block contaminants. For the prospective study, 63.2% of extraneous tissue was presumed to be from a different case, and in the retrospective study, 48.5% was presumed to be from a different case. Over 90% of extraneous tissue was thought to originate from the pathology laboratory. The degree of diagnostic difficulty caused by extraneous tissue was judged to be severe in 0.4% of slides in the prospective study and 0.1% of slides in the retrospective study. In the prospective study, it could not be determined whether the tissue in the diagnostic sections was extraneous in 0.6% of slides, and in the retrospective study, it could not be determined whether tissue in the diagnostic sections was extraneous in 0.1%. CONCLUSIONS: This study has documented the frequency, type, origin, source, and diagnostic difficulty of extraneous tissue and presents benchmarks of extraneous tissue experienced in the general practice of surgical pathology.

Databases, Factual↗

Prevalence of low bone mass in healthy Indian population.

Osteoporosis is a major problem of health care delivery services, both in the developed and developing countries. The first normative reference database of bone mineral density in the Indian women and men was established using digital x-ray radiogrammetry. Further analysis of this database revealed that 29.9% of women and 24.3% of men between the age of 20 and 79 years had low bone mass. About 50% women and 36% of men over 50 years of age were noted to have low bone mass. The observations of this study suggest that there is higher prevalence of low bone man in the Indian population compared to the western population.

Bone Density↗

Numerical description of selected endo- and ectocranial dimensions in Homo sapiens and the three Homo heidelbergensis: Kabwe, Atapuerca and Petralona.

Investigation of hominid cranial morphology is of particular importance for those dealing with questions concerning both ontogenetic and phylogenetic aspects in the genus Homo. The present study provides a numerical description of several regions of extant human crania and, in addition, mid-Pleistocene crania, given in distances and angles. This study is seen as a basic preparatory work that is most useful for further investigation on cranial development in hominids. The sample used consisted of 60 recent adult human crania as well as stereolithographic models of three H. heidelbergensis crania: Kabwe, Atapuerca and Petralona. 12 ecto- and 20 endocranial landmarks were selected and 3D-coordinates taken on each cranium using a 3D Polhemus 3Space FASTRAK tracking system. From the resulting data set, 21 ectocranial and 17 endocranial distances were calculated, in addition to 41 angles of the ectocranium and 21 angles of the endocranium; the measurements are presented in tables, serving as a reference database.

Adult↗

[Timeliness of 5,979 surgical pathology reports].

OBJECTIVE: To analyze the influence of prelaboratory and intralaboratory factors on the turnaround time of the reports in order to develop a reference database for continuous quality improvement, a retrospective study of the timeliness was reported. METHODS: Using cluster sampling of a total of 5,979 pathology reports selected by sampling a single month's reports from each quarter of the year 2000, of which there were 5,250 cases from routine biopsy and 729 cases from operative specimen. The timeliness and the factors that influence the turnaround time of the two types of surgical pathology reports were analyzed. RESULTS: 4,872 pathology reports of 5,250 routine biopsy cases were completed in 3 working days, and 613 of 729 cases of the operative specimens were completed in 4 working days. The percentage was 92.8% and 84.1% respectively. Factors that significantly contributed to the increase in turnover time of biopsy reports included request of immunohistochemical staining, delayed arrival of the operative specimen at the laboratory after frozen section, additional recutting, intradepartment consultation and decalcification etc. As for the operative cases, several factors were associated with delayed report: second day arrival of the operative specimen at the laboratory after frozen section, lack of the adequate clinical history, request for immunohistochemical staining etc. CONCLUSIONS: The majority of surgical pathology reports in the department can be completed timely and the timeliness meets the general standard. Only about 10 percent of the reports were delayed because of some prelaboratory and intralaboratory factors, for which there were 33.5% and 66.5% respectively for routine biopsy, and 50.9% and 49.1% respectively for operative specimen.

Humans↗

The relative sensitivity of four benthic invertebrates to metals in spiked-sediment exposures and application to contaminated field sediment.

The relative sensitivity of four benthic invertebrates (Hyalella azteca, Chironomus riparius, Hexagenia spp., and Tubifex tubifex) was determined for Cd, Cu, and Ni in water-only and in spiked-sediment exposures. Survival (median lethal concentrations [LC50s] and the concentrations estimated to be lethal to 25% of test organisms [LC25s]), and endpoints for growth and reproduction (mean inhibitory concentrations [IC25s]) were compared. The sensitivities differed depending on the species and metal, although some trends emerged. In water-only exposures, H. azteca is the most sensitive species to cadmium and nickel, with mean LC50s of 0.013 and 3.6 mg/L, respectively; C. riparius is the most sensitive species to copper, with a mean LC50 of 0.043 mg/L. In the spiked-sediment exposures, the order in decreasing sensitivity to copper is Hyalella = Hexagenia < Chironomus < Tubifex for survival and growth/reproduction. For cadmium, the order in decreasing sensitivity is Hyalella = Chironomus < Hexagenia < Tubifex, and for nickel is Hyalella << Hexagenia < Chironomus < Tubifex. Chironomus riparius and Hexagenia spp. survival can be used to distinguish between toxicity caused by different metals. Species test responses in field-collected sediment(Collingwood Harbour, ON, Canada) were examined in an attempt to determine the causative agent of toxicity throughout, using the established species sensitivities. Sediment toxicity was categorized first by comparing species responses to those established for a reference database. Test responses in the field-collected sediment do not support causality by Cu, a suspected toxicant based on comparison of sediment chemistry with sediment quality guidelines.

Animals↗

Mistletoe in cancer - a systematic review on controlled clinical trials.

BACKGROUND: Mistletoe preparations are among the most widely used unconventional cancer therapies in Central Europe. Their clinical effectiveness, however, is controversial. OBJECTIVE: To investigate whether prospective controlled clinical trials provide evidence for efficacy of mistletoe therapy in cancer. DESIGN: Systematic review. MATERIAL AND METHODS: Search of 11 electronic databases, reference lists and expert consultations. Criteria based analysis was performed to assess methodological quality of the studies. RESULTS: Twenty-three studies were identified: 16 randomized, 2 quasi-randomized and 5 non-randomized. Cancer sites included breast, lung, stomach, colon, rectum, head and neck, kidney, bladder, melanoma, glioma, and genital. Among these studies, statistically significant positive outcomes were reported for survival (n = 8), tumor remission (n = 1), overall quality of life (QOL) (n = 3), and QOL in relation to side effects during cytoreductive therapy (n = 3). Further, positive trends were reported for survival (n = 8), disease-free-survival (n = 1), and tumor remission (n = 2). Several studies reported no effect on survival (n = 4), disease-free-survival (n = 1), recurrence (n = 2), remission (n = 3), and QOL (n = 1). One study showed a negative trend for disease-free-survival. However, methodological quality of the studies was sometimes far below the standard that is today regarded as optimal or necessary. In view of substantial heterogeneity of the studies and potential positive and negative biases, we considered effect size estimation by quantitative synthesis to be unreliable and decided on a non-quantitative synthesis and discussion. Mistletoe therapy was well tolerated, and no major side effects were noted. CONCLUSIONS: Among 23 identified studies evaluated for clinically relevant outcome measures, 12 studies showed one or more statistically significant, positive results, another 7 studies showed at least one positive trend, 3 showed no effect and 1 had a negative trend. All studies, however, suffered from methodological shortcomings to some degree, and many of the studies are not conclusive. As several reasonably well conducted studies indicate beneficial effects, further properly designed trials should be encouraged. Future controlled studies should take into account the methodological limitations and potential biases of these past mistletoe trials.

Antineoplastic Agents↗

Systematic review of controlled trials on the effectiveness of fluoride gels for the prevention of dental caries in children.

Fluoride gels have been widely used since the 1970s. The aim of this review was to assess the effectiveness and safety of fluoride gels in the prevention of dental caries in children and to examine factors potentially modifying their effectiveness. Relevant randomized or quasi-randomized trials were identified without language restrictions by searching multiple databases, reference lists of articles, and journals and by contacting selected authors and manufacturers. Trials with blind outcome assessment comparing fluoride gel with placebo or no treatment for at least one year and involving children under seventeen years of age were selected. Inclusion decisions, quality assessment, and data extraction were duplicated in a random sample of one third of studies, and consensus was achieved by discussion or a third party. Random effects meta-analyses were performed where data could be pooled. Potential sources of heterogeneity were examined in random effects meta-regression analyses. The main outcome was caries increment measured by the change in decayed, missing, and filled permanent tooth surfaces (D(M)FS). The primary measure of effect was the prevented fraction (PF) that is the difference in mean caries increment between the treatment and control groups expressed as a percentage of the mean increment in the control group. Potential adverse effects and unacceptability of treatment were also recorded. Twenty-five studies were included, involving 7,747 children. For the twenty-three that contributed data for meta-analysis, the D(M)FS pooled prevented fraction estimate was 28 percent (95 percent CI, 19 percent to 37 percent; p < 0.0001). There was clear heterogeneity, confirmed statistically (p < 0.0001). The effect of fluoride gel varied according to type of control group used, with D(M)FS PF on average being 19 percent (95 percent CI, 5 percent to 33 percent; p < 0.009) higher in non-placebo controlled trials. Only two trials reported on adverse events. There is clear evidence of a caries-inhibiting effect of fluoride gel. The best estimate of the magnitude of this effect, based on the fourteen placebo-controlled trials, is a 21 percent reduction (95 percent CI, 14 to 28 percent) in D(M)FS. This corresponds to an NNT of two (95 percent CI, 1 to 3) to avoid one D(M)FS in a population with a caries increment of 2.2 D(M)FS/year, or an NNT of twenty-four (95 percent CI, 18 to 36) based on an increment of 0.2 D(M)FS/year. However, further work is needed to identify and quantify potential harmful effects of fluoride gels.

Adolescent↗

[Prescription of drugs not appropriate for children in a Pediatric Intensive Care Unit].

OBJECTIVE: To assess the extent of use of drugs not appropriate for children in prescriptions issued in a tertiary pediatric intensive care unit (PICU), according to FDA standards. METHODS: Observational cross-sectional study. The prescriptions issued to all patients admitted to the PICU at Hospital de Clínicas de Porto Alegre, Brazil, over a six-week period were assessed. Patients' age, sex, weight, prior disease, reason for admission to the PICU and pediatric index of mortality (PIM) were recorded, as were all drugs prescribed, their indications, presentations, doses, frequencies and means of administration. Adequacy for prescription of drugs in three pediatric age ranges was defined according to USA Food and Drug Administration (FDA) approval classification, based on the USP DI 2001 drug reference database. RESULTS: Data were obtained in the months of July and August 2002, on different days, for six consecutive weeks, based on prescriptions issued to 51 patients in 54 admissions to the PICU. Median patient age was 10.5 months; 61% of patients were male. Two thirds of patients (65%) presented prior disease. 87% of admissions were due to clinical reasons, of which 57% were respiratory complaints. A total of 747 prescription items were registered, with prevalence of 10.5% for non-approved uses and 49.5% for off-label uses. No statistically significant difference was found in the distribution of prevalence of irregular prescription either by the three age ranges or by level of severity of disease at admission (according to PIM risk categories). CONCLUSIONS: The high prevalence of prescription of drugs not appropriate for children confirms, in the Brazilian context, the inadequate and inadvertent use of drugs either not approved or off-label for PICU use. This demonstrates the need to encourage further studies on the quality, efficacy and safety of drugs for pediatric use.

Adolescent↗

PC CLIN-SIM: a toolbook based clinical simulation environment.

The Departments of Computer Medicine, Health Care Sciences, Medicine, and Electrical Engineering & Computer Science at the George Washington University have joined forces to create a clinical simulation program. The purpose of this program is to provide experience in the management of complex patient populations (eg geriatrics). A number of simulation programs are available commercially, however none provide adequate geriatric content, or were deemed to lack functionality important to the developers. The immediate goal of this effort was to create a computer-based, core curriculum in geriatric medicine for medical and allied health students. The curriculum includes case simulations linked to a comprehensive reference database. The development objectives were to create an intuitive, friendly, consistent user interface which could serve as a shell for additional content areas. In order to increase fidelity, free text entry and time simulation were included.

Computer Graphics↗

Automatic quantification of myocardial perfusion stress-rest change: a new measure of ischemia.

UNLABELLED: In myocardial perfusion SPECT (MPS), ischemia is typically quantified as the difference between stress and rest defect sizes obtained by separate comparisons with stress and rest normal limits. Such an approach is not optimal because images are not compared directly with each other and a complex set of stress and rest normal limits is required. METHODS: We developed a fully automatic technique to quantify stress-rest change. We applied it to 204 patients whose SPECT images were acquired using a same-day dual-isotope (99m)Tc/(201)Tl protocol and on whom coronary angiography had been performed. A 10-parameter registration of rest and stress images was performed by an iterative search of best translational, rotational, scaling, and optimal stress-rest count normalization parameters. Identical stress-rest 3-dimensional left ventricle (LV) contours were automatically derived from stress images. Integrated deficit counts (normalized rest-stress) within the LV volume were derived from registered image pairs. A global measure of ischemia (ISCH) was calculated as the ratio of the total deficit stress LV counts to the total rest LV counts. RESULTS: Registration and derivation of quantitative measures were fully automatic. The average processing time was <40 s on a 2-GHz processor. When compared for prediction of stenosis, the area under the receiver operating characteristic curve (0.88 +/- 0.03) was significantly better for ISCH than that obtained by existing quantitative approaches, which use reference databases (0.80-0.82 +/- 0.03). The normalized stress-rest change could be visualized and localized directly on raw patient images using overlay display. CONCLUSION: Automatic stress-rest MPS image registration allows a direct estimation of ischemia from SPECT that does not require comparisons with normal limits.

Adenosine↗

Lipomic profiling in drug discovery, development and clinical trial evaluation.

Dysregulation of lipid metabolism plays a crucial role in the progression of many diseases and in adverse drug response. Changes in lipid metabolism leading to disease are often not detected using biomarker analyses because these changes are defined by a subtle, long-term shift in the concentrations of many metabolites simultaneously. The application of the principals of 'omics to the study of lipids, which include the development of comprehensive, high-throughput assays and centralized reference databases, is beginning to produce an integrated and actionable knowledge of lipids and their relationship to pathology. These analytical tools and the assembled knowledge will enable the discovery, development and testing of drugs to be conducted with a deeper knowledge of their effects on lipid metabolism.

Animals↗

[Identification of a very short YCAII allele in the northern Polish population].

The YCAII system is one of the Y-chromosomal STR markers with dinucleotide repetitive units and due to the duplication on the chromosome, its amplification provides two polymorphic products. Due to the high polymorphism, YCAII was included in the Y-STR Haplotype Reference Database (http://www.ystr.org) and significantly increased discrimination power of the collected haplotypes. During studies on the Y-STR polymorphism in the Polish population, a very short YCAII allele with relatively low stutter was identified. Sequencing revealed the presence of 11 dinucleotide repetitive units characteristic of this system. Among 3998 extended haplotypes collected in the database, this allele was found only in the population of south-western Germany. Similarities between the haplotypes possessing the YCAII*11 allele suggest their common origin.

Alleles↗

Content-based image retrieval in medical applications.

OBJECTIVES: To develop a general structure for semantic image analysis that is suitable for content-based image retrieval in medical applications and an architecture for its efficient implementation. METHODS: Stepwise content analysis of medical images results in six layers of information modeling incorporating medical expert knowledge (raw data layer, registered data layer, feature layer, scheme layer, object layer, knowledge layer). A reference database with 10,000 images categorized according to the image modality, orientation, body region, and biological system is used. By means of prototypes in each category, identification of objects and their geometrical or temporal relationships are handled in the object and the knowledge layer, respectively. A distributed system designed with only three core elements is implemented: (i) the central database holds program sources, processing scheme descriptions, images, features, and administrative information about the workstation cluster; (ii) the scheduler balances distributed computing; and (iii) the web server provides graphical user interfaces for data entry and retrieval, which can be easily adapted to a variety of applications for content-based image retrieval in medicine. RESULTS: Leaving-one-out experiments were distributed by the scheduler and controlled via corresponding job lists offering transparency regarding the viewpoints of a distributed system and the user. The proposed architecture is suitable for content-based image retrieval in medical applications. It improves current picture archiving and communication systems that still rely on alphanumerical descriptions, which are insufficient for image retrieval of high recall and precision.

Databases as Topic↗

Potential use of a host associated molecular marker in Enterococcus faecium as an index of human fecal pollution.

Several genotypic and phenotypic microbial source tracking (MST) methods have been proposed and utilized to differentiate groups of microorganisms, usually indicator organisms, for the purpose of tracking sources of fecal pollution. Targeting of host-specific microorganisms is one of the approaches currently being tested. These methods are useful as they circumvent the need to isolate individual microorganisms and do not require the establishment of reference databases. Several studies have demonstrated that the presence and distribution of Enterococcus spp. in feces seems to be influenced by the host species. Here, we present a method for detection of genetic sequences in culturable enterococci capable of identifying human sources of fecal pollution in the environment. The human fecal pollution marker designed in this study targets a putative virulence factor, the enterococcal surface protein (esp), in Enterococcus faecium. This gene was detected in 97% of sewage and septic samples but was not detected in any livestock waste lagoons or in bird or animal fecal samples. Epidemiological studies in recreational and groundwaters have shown enterococci to be useful indicators of public health risk for gastroenteritis. By identifying the presence of human fecal pollution, and therefore the possible presence of human enteric pathogens, this marker allows for further resolution of the source of this risk.

DNA, Bacterial↗

The effects of iodine on intelligence in children: a meta-analysis of studies conducted in China.

This study quantifies the effects of iodine on the intellectual development of children using a systematic manual literature search of Chinese publications related to iodine deficiency disorders. The Chinese Medical Reference Database, Medline, and Cochrane library were searched electronically in Chinese and English. Inclusion criteria included: studies conducted in China, comparing children (<16 ys) living in naturally iodine sufficient (IS) with those in severely iodine deficient (ID) areas, or children in ID areas born before and after the introduction of iodine supplementation. Intelligent Quotient (IQ) was measured using Binet or Raven Scales. The iodine sufficient control groups were comparable socially, economically, and educationally with the study groups. Random effects models were used in the meta-analysis. Effect size was the standard deviation IQ point (SIQP), which is equivalent to 15 IQ. Thirty-seven reported studies, total 12,291 children, were analysed. The effect size was an increase of 0.83, 0.82, and 0.32 SIQP respectively, for the children living in IS communities compared with those living in ID areas with no iodine supplementation, with inadequate iodine supplementation, or children who had received iodine during their mothers' pregnancy and after birth. These equal to 12.45, 12.3, 4.8 IQ points. Compared with that of children whose mothers were persistently exposed to ID, the total effect size of the 21 entries was an increase of 0.58 SIQP (8.7 IQ points) in the group receiving iodine supplementation during pregnancy. Furthermore, there was an increase on 1.15 SIQP of Binet or 0.8 SIQP on Raven Scale (17.25 or 12 IQ points) for children born more than 3.5 years after iodine supplementation program was introduced. The level of iodine nutrition plays a crucial role in the intellectual development of children. The intelligence damage of children exposed to severe ID was profound, demonstrated by 12.45 IQ points loss and they recovered 8.7 IQ points with iodine supplementation or IS before and during pregnancy. Iodine supplementation before and during pregnancy to women living in severe ID areas could prevent their children from intelligence deficit. This effect becomes evident in children born 3.5 years after the iodine supplementation program was introduced.

Adolescent↗