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AIMS: Specific patterns in incidence may reveal environmental explanations for type 1 diabetes incidence. We aimed to study type 1 diabetes incidence in European childhood populations to assess whether an increase could be attributed to either period or cohort effects. METHODS: Nineteen EURODIAB centres provided single year incidence data for ages 0-14 in the 25-year period 1989-2013. Case counts and person years were classified by age, period and cohort (APC) in 1-year classes. APC Poisson regression models of rates were fitted using restricted cubic splines for age, period and cohort per centre and sex. Joint models were fitted for all centres and sexes, to find a parsimonious model. RESULTS: A total of 57,487 cases were included. In ten and seven of the 19 centres the APC models showed evidence of nonlinear cohort effects or period effects, respectively, in one or both sexes and indications of sex-specific age effects. Models showed a positive linear increase ranging from approximately 0.6 to 6.6%/year. Centres with low incidence rates showed the highest overall increase. A final joint model showed incidence peak at age 11.6 and 12.6 for girls and boys, respectively, and the rate-ratio was according to sex below 1 in ages 5-12. CONCLUSION: There was reasonable evidence for similar age-specific type 1 diabetes incidence rates across the EURODIAB population and peaks at a younger age for girls than boys. Cohort effects showed nonlinearity but varied between centres and the model did not contribute convincingly to identification of environmental causes of the increase.
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Diabetes Mellitus Tipo 1 , Masculino , Feminino , Criança , Humanos , Lactente , Recém-Nascido , Pré-Escolar , Adolescente , Diabetes Mellitus Tipo 1/epidemiologia , Incidência , Seguimentos , Sistema de Registros , ConvulsõesRESUMO
Neonatal diabetes (ND) appears during the first months of life and is caused by a single gene mutation. It is heterogenous and very different compared to other forms of multi-factorial or polygenic diabetes. Clinically, this form is extremely severe, however, early genetic diagnosis is pivotal for successful therapy. A large palette of genes is demonstrated to be a cause of ND, however, the mechanisms of permanent hyperglycemia are different. This review will give an overview of more frequent genetic mutations causing ND, including the function of the mutated genes and the specific therapy for certain sub-forms.
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Steroid 5-α-reductase-2 (5-ARD) deficiency is a result of mutations of the SRD5A2 gene. It causes the disorder of sexual differentiation (DSD) in 46,XY individuals with a variable genital phenotype. We present two siblings with female external genitalia at birth and bilateral inguinal testes, raised as females. These are the first molecularly characterized patients from the Republic of North Macedonia (RN Macedonia) with a different clinical course due to the time of the diagnosis. Diagnosis of Patient 1 was based upon the detection of bilateral inguinal testes and testosterone/dihidrotestosterone ratio. Sex reversal was initiated by testes removal at the age of 20 months. Breast implantation and vaginoplasty were performed in adolescence and the girl is comfortable with the female sex. Her sibling, Patient 2, raised as a girl, was clinically assessed at 11.5 years due to the growth of phalus, deep voice and Adam's apple enlargement. No change of gender was accepted. Complex molecular analysis including multiplex quantitative fluorescent polymerase chain reaction (PCR) screening for sex chromosome aneuploidies and SRY presence, Sanger sequencing combined with multiplex ligation-dependent probe amplification (MLPA), microarray-based comparative genomic hybridization (aCGH), and real-time PCR analysis for detection of exon copy number changes confirmed a novel c.146C>A (p.Ala49Asp) point mutation in the first exon inherited from the mother, and complete deletion of the first exon and adjacent regions inherited from the father. Novel genotype causing 5-ARD is presented. Genetic analysis is useful for the diagnosis and timely gender assignment in patients with 5-ARD. However, final gender assignment is difficult and requires combined medical interventions.
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Arterial tortuosity syndrome (ATS) is a rare autosomal recessive disorder caused by mutations in the solute carrier family 2 member 10 (SLC2A10) gene encoding a glucose/ascorbic acid transporter. The clinical features of ATS are mild-to-severe tortuosity of the large and medium arteries throughout the body, accompanied by dysmorphisms and joint laxity. Vascular changes in different parts of the body lead to stenosis and/or aneurysms requiring difficult surgical procedures. Here we present two new patients with ATS from two unrelated families. Patient 1 presented at 10 years of age with headache and typical physical appearance, delicate skeleton, large visible pulsation of the carotid arteries in the neck, and joint laxity. On computed tomography (CT) angiography she had severe tortuosity of the aortal branches and cerebral arteries, but no significant tortuosity of the pulmonary arteries. Two cousins of the girl carried the same homozygous c.254T>C, p.(Leu85Pro) mutation in SLC2A10, however, they additionally had a severe involvement of the pulmonary vessels. Patient 2 was a 9-year-old girl diagnosed with severe tortuosity and stenosis of the pulmonary arteries and progressive myocardiopathy. Her physical appearance was very similar to Patient 1, except that she also had growth retardation. After long-term follow-up by cardiologists, she underwent cardiac surgery abroad, with an unfavorable outcome. Homozygosity for the c.685C>T, p.(Arg229*) mutation in the SLC2A10 gene was detected. Consanguinity was disclosed within both families. Our findings confirm the intrafamilial phenotype variability of ATS. A novel finding is the severe tortuosity of cerebral arteries causing migraine that has not been described before in a child with ATS.
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We present a boy with mild hyperglycemia detected during an upper respiratory infection. Novel splicing mutation in the intron 1 of the GCK gene (c.45+1G>A) was detected, and was subsequently confirmed in his father. This is the first case of genetically confirmed Macedonian family with MODY.
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Diabetes Mellitus Tipo 2/genética , Glucoquinase/genética , Mutação , Pré-Escolar , Diabetes Mellitus Tipo 2/terapia , Feminino , Teste de Tolerância a Glucose , Grécia , Humanos , Hiperglicemia/genética , MasculinoRESUMO
BACKGROUND: The month of diagnosis in childhood type 1 diabetes shows seasonal variation. OBJECTIVE: We describe the pattern and investigate if year-to-year irregularities are associated with meteorological factors using data from 50 000 children diagnosed under the age of 15 yr in 23 population-based European registries during 1989-2008. METHODS: Tests for seasonal variation in monthly counts aggregated over the 20 yr period were performed. Time series regression was used to investigate if sunshine hour and average temperature data were predictive of the 240 monthly diagnosis counts after taking account of seasonality and long term trends. RESULTS: Significant sinusoidal pattern was evident in all but two small centers with peaks in November to February and relative amplitudes ranging from ± 11 to ± 38% (median ± 17%). However, most centers showed significant departures from a sinusoidal pattern. Pooling results over centers, there was significant seasonal variation in each age-group at diagnosis, with least seasonal variation in those under 5 yr. Boys showed greater seasonal variation than girls, particularly those aged 10-14 yr. There were no differences in seasonal pattern between four 5-yr sub-periods. Departures from the sinusoidal trend in monthly diagnoses in the period were significantly associated with deviations from the norm in average temperature (0.8% reduction in diagnoses per 1 °C excess) but not with sunshine hours. CONCLUSIONS: Seasonality was consistently apparent throughout the period in all age-groups and both sexes, but girls and the under 5 s showed less marked variation. Neither sunshine hour nor average temperature data contributed in any substantial way to explaining departures from the sinusoidal pattern.
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Diabetes Mellitus Tipo 1/diagnóstico , Sistema de Registros , Estações do Ano , Adolescente , Criança , Pré-Escolar , Europa (Continente) , Feminino , Humanos , Lactente , Masculino , Fotoperíodo , TemperaturaRESUMO
Wolf-Hirschhorn syndrome (WHS) is a rare chromosomal disorder caused by terminal deletion of the short arm of chromosome 4. The clinical picture includes growth retardation, severe mental retardation, characteristic "Greek helmet" like face, seizures and midline defects in the brain, heart, palate and genitalia. Recently-used molecular techniques increase the number of diagnosed cases due to the detection of smaller deletions. The severity of the clinical presentation is variable depending on the haploinsufficiency of genes in a deleted region. We present six children with WHS with variable clinical appearance. The assessment of several elements (facial dysmorphism, mental retardation, additional congenital anomalies) provided classification into minor, mild or severe forms. Three of the children had a visible cytogenetic deletion on chromosome 4p, two had microdeletions detected with fluorescent in situ hybridization (FISH), and one child with a less characteristic clinical picture had a mosaic type of the deletion. Correlation between the clinical presentation and the length of the deleted region was confirmed.
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Congenital hypothyroidism (CH) is the most common preventable cause of mental retardation in children. Diagnosis is difficult at birth without neonatal screening. Neonatal thyroid screening was established in Prilep, Republic of Macedonia as an integral part of the nationwide screening program. To estimate the prevalence of CH in this region, neonatal thyroid screening was performed on 9757 newborns, during the period 2002-2011. The DELFIA method was applied to measure the thyroid-stimulating hormone (TSH) concentration in dried blood spot samples on standard filter paper taken 48 hours after birth by heel-stick. The TSH cut-off level was 10 mU/L. The neonatal thyroid screening coverage was 93.4%. Eight newborns with CH were detected, with an incidence of 1:1220 live births, significantly higher compared to the nationwide results 1:2602. The TSH level was not significantly dependent on the gender of the newborn. There was a statistically significant difference between the TSH level and the timing of newborn screening sampling (p <0.05) and between the TSH level and the newborn birth weight (p = 0.01). One point ninety-two percent of newborns with TSH levels above 5 mU/L indicated an iodine sufficiency in Prilep. The incidence of CH in Prilep, which is higher when compared with that reported in surrounding countries, might be a consequence of the higher percentage of the Romany population in this region. Further analysis of this population in other regions is warranted.
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AIMS/HYPOTHESIS: The aim of the study was to describe 20-year incidence trends for childhood type 1 diabetes in 23 EURODIAB centres and compare rates of increase in the first (1989-1998) and second (1999-2008) halves of the period. METHODS: All registers operate in geographically defined regions and are based on a clinical diagnosis. Completeness of registration is assessed by capture-recapture methodology. Twenty-three centres in 19 countries registered 49,969 new cases of type 1 diabetes in individuals diagnosed before their 15th birthday during the period studied. RESULTS: Ascertainment exceeded 90% in most registers. During the 20-year period, all but one register showed statistically significant changes in incidence, with rates universally increasing. When estimated separately for the first and second halves of the period, the median rates of increase were similar: 3.4% per annum and 3.3% per annum, respectively. However, rates of increase differed significantly between the first half and the second half for nine of the 21 registers with adequate coverage of both periods; five registers showed significantly higher rates of increase in the first half, and four significantly higher rates in the second half. CONCLUSIONS/INTERPRETATION: The incidence rate of childhood type 1 diabetes continues to rise across Europe by an average of approximately 3-4% per annum, but the increase is not necessarily uniform, showing periods of less rapid and more rapid increase in incidence in some registers. This pattern of change suggests that important risk exposures differ over time in different European countries. Further time trend analysis and comparison of the patterns in defined regions is warranted.
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Diabetes Mellitus Tipo 1/epidemiologia , Necessidades e Demandas de Serviços de Saúde/organização & administração , Sistema de Registros/estatística & dados numéricos , Adolescente , Distribuição por Idade , Criança , Proteção da Criança , Europa (Continente)/epidemiologia , Feminino , Planejamento em Saúde , Humanos , Incidência , Masculino , Estudos Prospectivos , Fatores de Risco , Distribuição por Sexo , Taxa de SobrevidaRESUMO
The oral-facial-digital (OFD) syndrome is a heterogeneous group of abnormalities that share anomalies of the oral cavity, face and digits of hands and feet. On the basis of other anomalies of brain, kidneys, limbs, eyes and other organs, at least 13 subgroups have been described. We here describe four unrelated patients with this syndrome, who have the typical facial, oral and digital anomalies and also anomalies of other organs and systems. Facial features, digital malformations, as well as the existence of additional malformations all of which can be classified into different subgroups. The report points out the difficulty in delineation of the subtypes of OFD syndrome because of the overlapping features between OFD subgroups.
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Síndrome de Alstrom/genética , Síndrome de Alstrom/patologia , Cegueira/genética , Mutação , Proteínas/genética , Acantose Nigricans/etiologia , Alopecia/etiologia , Cegueira/etiologia , Proteínas de Ciclo Celular , Criança , Análise Mutacional de DNA , Feminino , Hirsutismo/etiologia , Humanos , FenótipoRESUMO
OBJECTIVE: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control. METHODS: Clinical data and questionnaires were completed by adolescents, parents/carers and diabetes teams in 21 international centres. HbA1c was measured centrally. RESULTS: A total of 2062 adolescents completed questionnaires (age 14.4 +/- 2.3 yr; diabetes duration 6.1 +/- 3.5 yr). Mean HbA 1c = 8.2 +/- 1.4% with significant differences between centres (F = 12.3; p < 0.001) range from 7.4 to 9.1%. There was a significant correlation between parent (r = 0.20) and adolescent (r = 0.21) reports of their perceived ideal HbA1c and their actual HbA1c result (p < 0.001), and a stronger association between parents' (r = 0.39) and adolescents' (r = 0.4) reports of the HbA1c they would be happy with and their actual HbA1c result. There were significant differences between centres on parent and adolescent reports of ideal and happy with HbA1c (8.1 < F > 17.4;p < 0.001). A lower target HbA1c and greater consistency between members of teams within centres were associated with lower centre HbA1c (F = 16.0; df = 15; p < 0.001). CONCLUSIONS: Clear and consistent setting of glycaemic targets by diabetes teams is strongly associated with HbA1c outcome in adolescents. Target setting appears to play a significant role in explaining the differences in metabolic outcomes between centres.
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Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/psicologia , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Adolescente , Glicemia/análise , Glicemia/efeitos dos fármacos , Criança , Estudos Transversais , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pais/psicologia , Guias de Prática Clínica como Assunto , Resultado do TratamentoRESUMO
Congenital hypothyroidism (CH) is the most common preventable cause of mental retardation. Early diagnosis and treatment are crucial to the prevention of severe intellectual deficit. Neonatal screening in a blood spot from the heel of the newborn between the 2nd and 5th day after birth and determination of thyroid stimulation hormone (TSH) level by fluoroimmunoassay (DELFIA method) is the commonly used approach for the timely detection and therapy of congenital hypothyroidism. Over the period April 2002 - December 2004 results of 27,782 samples were analysed. They were obtained from 5 hospitals in the Republic of Macedonia (Obstetrics and Gynaecology Clinic, Clinical Centre, Skopje; Cair Obstetrics and Gynaecology Hospital, Mala Bogorodica Hospital and hospitals within the cities of Bitola and Prilep). Over the period January 2005 - December 2007 the analysis of 50,732 samples covered all obstetrics hospitals in Macedonia. For the first period analysed (April 2002 - December 2004) we evaluated the sensitivity and specificity of the biochemical method applied for neonatal screening for CH. In our study TSH was assayed by DELFIA fluorometric kits. The cut-off value in our laboratory was 15 mU/L. We compared coverage, timeliness of programme indicators (age at sampling, recall and treatment initiation, timing of specimen delivery and laboratory results) and specimen quality with international standards. Recall rate, sensitivity, specificity, positive predictive values and relative incidence rate for CH were calculated. The established method was deemed highly sensitive and highly specific. During the period of analysis in our study, 28 cases were detected or an incidence rate of 1 : 2,804 was calculated. Treatment was initiated on the 13th day on average (between the 5th and 35th day).
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Hipotireoidismo Congênito/diagnóstico , Triagem Neonatal , Humanos , Recém-Nascido , Triagem Neonatal/métodos , Triagem Neonatal/organização & administração , República da Macedônia do Norte , Sensibilidade e Especificidade , Tireotropina/sangueRESUMO
AIMS: To assess the importance of family factors in determining metabolic outcomes in adolescents with Type 1 diabetes in 19 countries. METHODS: Adolescents with Type 1 diabetes aged 11-18 years, from 21 paediatric diabetes care centres, in 19 countries, and their parents were invited to participate. Questionnaires were administered recording demographic data, details of insulin regimens, severe hypoglycaemic events and number of episodes of diabetic ketoacidosis. Adolescents completed the parental involvement scale from the Diabetes Quality of Life for Youth--Short Form (DQOLY-SF) and the Diabetes Family Responsibility Questionnaire (DFRQ). Parents completed the DFRQ and a Parental Burden of Diabetes score. Glycated haemoglobin (HbA(1c)) was analysed centrally on capillary blood. RESULTS: A total of 2062 adolescents completed a questionnaire, with 2036 providing a blood sample; 1994 parents also completed a questionnaire. Family demographic factors that were associated with metabolic outcomes included: parents living together (t = 4.1; P < 0.001), paternal employment status (F = 7.2; d.f. = 3; P < 0.001), parents perceived to be over-involved in diabetes care (r = 0.11; P < 0.001) and adolescent-parent disagreement on responsibility for diabetes care practices (F = 8.46; d.f. = 2; P < 0.001). Although these factors differed between centres, they did not account for centre differences in metabolic outcomes, but were stronger predictors of metabolic control than age, gender or insulin treatment regimen. CONCLUSIONS: Family factors, particularly dynamic and communication factors such as parental over-involvement and adolescent-parent concordance on responsibility for diabetes care appear be important determinants of metabolic outcomes in adolescents with diabetes. However, family dynamic factors do not account for the substantial differences in metabolic outcomes between centres.
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Glicemia/metabolismo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Adolescente , Automonitorização da Glicemia/métodos , Automonitorização da Glicemia/psicologia , Criança , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/psicologia , Feminino , Humanos , Masculino , Relações Pais-Filho , Aceitação pelo Paciente de Cuidados de Saúde , Qualidade de Vida/psicologia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Fluorescent in situ hybridisation (FISH) is a complementary cytogenetic method which has an important role in discovering unsolved cases of mental retardation and multiple anomalies. The ability of this method to detect complex and cryptic chromosomal rearrangements exceeds the resolution of the usual cytogenetic banding techniques; therefore it has a wide implementation in modern cytogenetic laboratories - in routine work, as well as for research purposes. We analysed 19 patients with microdeletion syndromes - 9 patients with Williams syndrome, 4 patients with Prader-Willi syndrome, and 6 patients with DiGeorge syndrome. On the basis of evaluation of facial dysmorphism and the presence of specific major anomalies, all the patients met the criteria for the diagnosis of the syndrome. FISH studies were performed, confirming the suspected syndrome in patients.
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Deleção Cromossômica , Síndrome de DiGeorge/diagnóstico , Hibridização in Situ Fluorescente , Síndrome de Prader-Willi/diagnóstico , Síndrome de Williams/diagnóstico , Síndrome de DiGeorge/genética , Feminino , Humanos , Masculino , Síndrome de Prader-Willi/genética , Síndrome de Williams/genéticaRESUMO
INTRODUCTION: Premature thelarche presents as an appearance of breasts and glandular tissue in girls before the age of 8 years. It is mostly a benign and transitory variation of premature sexual development. AIM OF THE STUDY: We evaluated a group of girls with premature thelarche for clinical and auxologic characteristics for a period of three years. We investigated the duration of the condition and eventual progression toward true idiopathic central precocious puberty. PATIENTS, MATERIALS, METHODS: At the Department of Endocrinology and Genetics at the Pediatric Clinic in Skopje, 127 girls with premature thelarche, from all over the country, were analyzed and followed-up for a period of 3 years (2000-2003). RESULTS AND CONCLUSIONS: Premature thelarche as a partial form of premature sexual development, in our study included 98 girls, and showed to be a benign condition, the girls are with normal height, slightly elevated weight, but with increased bone maturation and height velocity in the first year. A progression toward central precocious puberty was not registered. The duration of the condition was about two years in most of the girls, with a regression of enlarged breasts in smaller patients and with occurrence of normal puberty in older patients (Tab. 1, Fig. 3, Ref. 16). Full Text (Free, PDF) www.bmj.sk.
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Mama/crescimento & desenvolvimento , Maturidade Sexual , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Puberdade Precoce/diagnóstico , República da Macedônia do NorteRESUMO
BACKGROUND: Patients with Turner's syndrome receiving unopposed estrogens for the induction of feminization have an increased risk of endometrial carcinoma. Only seven patients who were not treated with estrogen replacement therapy have been reported to have developed endometrial carcinoma at different age levels. CASE: A young girl with Turner's syndrome phenotype, spontaneous puberty, and karyotype 45,X0/47,XXX from peripheral blood, after irregular menstrual cycles of 9 years, at the age of 21, was diagnosed with a non-invasive well-differentiated endometrial carcinoma confined to a hyperplastic endometrial polyp. Analysis of the ovarian tissue by FISH confirmed mosaicism: 45,X0/46,XX/47,XXX. CONCLUSION(S): The endogenous estrogen secretion from the ovaries might have caused malignancy in this case. Patients with Turner's syndrome with spontaneous menarche might carry a higher risk of endometrial carcinoma.
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Neoplasias do Endométrio/etiologia , Síndrome de Turner/complicações , Adulto , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Feminino , Humanos , Menarca , Síndrome de Turner/genética , Síndrome de Turner/patologiaRESUMO
OBJECTIVE: The objective of the investigation was to analyze theoretical exposures to hypolipidaemics in patients treated chronically with these drugs, using the database of the health insurance company. INVESTIGATED GROUP: From the database (with information on age, sex of the insured person, the number of packages and the type of hypolipidemic and year of issue of the prescription) of subjects insured at the Employees Health Insurance Skoda Mladá Boleslav comprising some 100,000 insured subjects in 1994-2000. Patients with long-term (more than one year) hypolipidaemic treatment were selected in years from 1995 to 1999. The group increased every year. In 1995 it comprised 668 cases in 1999, 2396 subjects. METHOD: The consumption of hypolipidaemics was expressed in defined daily doses (DDD). The authors investigated the ratio of chronically treated patients and the proportion of the following groups of patients according to their annual consumption in 1995-1999: group of of drug "vacation" (0 DDD) and the group with a low (< 121.7 DDD), medium (< 243.3 & > 121.7 DDD) and optimal (> 243.3 DDD) consumption of hypolipidaemics and their relationship to sex and age. For statistical ealuation software SPSS 10.1 was used. RESULTS: In the course of the investigation among the insured subjects the statin consumption increased 76 times and the consumption of fibrates 5 times. The ratio of consumption of resin derivatives and of nicotinic acid was negligible. The size of the group of subjects treated with hypolipidaemics for longer than one year increased from 0.8% in 1995 to 2.2% of the database. The average age increased from 55 to 59 years. The ratio of seniors (> or = 65 years) increased in the course of the investigation and reached 33% in 1999 of all members of the investigated group. The mean annual consumption of hypolipidaemics increased significantly as compared with 1995 and the interannual increase as compared with the previous year was statistically significant in 1997 and 1999. In 1999 it was 237 DDD/per consumer. A lower consumption was recorded in women and in seniors. Drug "vacations" were recorded in 6% of the insured subjects of the group and the frequency did not change significantly in the course of the investigation and no relationship with age and sex was found. A low exposure according to DDD was found in 20%, medium exposure in about 40% and optimal exposure in only one third of the subjects of the investigated group. CONCLUSION: The authors developed a method which makes it possible, when individual data of the health insurance company are available, to investigate the theoretical exposure to hypolipidaemics in insured subjects treated on a long-term basis with these drugs. The authors provided evidence that analysis of the database of the health insurance company can provide certain signals for further pharmacoepidemiological research and for application in a defined medical discipline. Some of the insured subjects are exposed to smaller doses than theoretically assumed. It is necessary to extend the investigation so that the results will better reflect the population of patients and prescribing physicians. Complete evaluation of cases with a low exposure from the aspect of morbidity and drug compliance will be also essential.
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Hipolipemiantes/uso terapêutico , Idoso , República Tcheca , Bases de Dados Factuais , Uso de Medicamentos , Feminino , Humanos , Seguro Saúde , MasculinoRESUMO
OBJECTIVE: It is unclear whether the demands of good metabolic control or the consequences of poor control have a greater influence on quality of life (QOL) for adolescents with diabetes. This study aimed to assess these relations in a large international cohort of adolescents with diabetes and their families. RESEARCH DESIGN AND METHODS: The study involved 2,101 adolescents, aged 10-18 years, from 21 centers in 17 countries in Europe, Japan, and North America. Clinical and demographic data were collected from March through August 1998. HbA(1c) was analyzed centrally (normal range 4.4-6.3%; mean 5.4%). Adolescent QOL was assessed by a previously developed Diabetes Quality of Life (DQOL) questionnaire for adolescents, measuring the impact of diabetes, worries about diabetes, satisfaction with life, and health perception. Parents and health professionals assessed family burden using newly constructed questionnaires. RESULTS: Mean HbA(1c) was 8.7% (range 4.8-17.4). Lower HbA(1c) was associated with lower impact (P < 0.0001), fewer worries (P < 0.05), greater satisfaction (P < 0.0001), and better health perception (P < 0.0001) for adolescents. Girls showed increased worries (P < 0.01), less satisfaction, and poorer health perception (P < 0.01) earlier than boys. Parent and health professional perceptions of burden decreased with age of adolescent (P < 0.0001). Patients from ethnic minorities had poorer scores for impact (P < 0.0001), worries (P < 0.05), and health perception (P < 0.01). There was no correlation between adolescent and parent or between adolescent and professional scores. CONCLUSIONS: In a multiple regression model, lower HbA(1c) was significantly associated with better adolescent-rated QOL on all four subscales and with lower perceived family burden as assessed by parents and health professionals.