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Puntos para una lectura rapida • Cualquier acto asistencial es un momento adecuado para repasar y actualizar el calendario vacunal. • La administracion simultanea de varias vacunas reduce el numero de visitas y aumenta la cobertura. • Para mejorar registros vacunales deberia haber un sistema centralizado a nivel nacional y un calendario vacunal unico. • Argumentar la importancia de la vacunacion por parte del personal sanitario es una buena estrategia para aumentar coberturas.

Laura Medina-Perucha,1,2 Tomàs López-Jiménez,1,2 Anna Sofie Holst,1,3 Constanza Jacques-Aviñó,1,2 Jordina Munrós-Feliu,4,5 Cristina Martínez-Bueno,5,6 Carme Valls-Llobet,7 Diana Pinzón-Sanabria,8 Mª Mercedes Vicente-Hernández,5 Anna Berenguera1,2,9 1Fundació Institut Universitari per a la recerca a l’Atenció Primà ria de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain; 2Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain; 3Universitat Pompeu Fabra, Barcelona, Spain; 4Atenció a la Salut Sexual i Reproductiva (ASSIR) Muntanya/La Mina, Institut Català de la Salut, Barcelona, Spain; 5Sexual and Reproductive Health Care Research Group (GRASSIR), Barcelona, Spain; 6Servei d’Atenció a la Salut Sexual i Reproductiva (ASSIR), Direcció Assistencial d’Atenció Primà ria, Institut Català de la Salut, Barcelona, Spain; 7Centro de Análisis y Programas Sanitarios (CAPS), Barcelona, Spain; 8SomiArte Taller, Barcelona, Spain; 9Departament d’Infermeria, Universitat de Girona, Girona, SpainCorrespondence: Laura Medina-Perucha, Gran Via de les Corts Catalanes 587 attic, Barcelona, 08007, Spain, Tel +34 934824253, Email lmedina@idiapjgol.orgIntroduction: Available evidence suggests that there might be an association between the stressors experienced during the COVID-19 syndemic and changes in menstrual patterns. The aim of this study was to assess self-reported menstrual alterations during the COVID-19 syndemic among women and people who menstruate aged 18– 55 in Spain.Materials and Methods: A cross-sectional online survey-based study was conducted (March–July 2021). Descriptive statistics were calculated and multivariate logistic regression models were constructed. This study was conducted as part of the “Equity and Menstrual Health in Spain” research project.Results: Among participants (N=17,455), 39.4% reported menstrual alterations since the start of the syndemic. Participants self-reporting long COVID-19 presented higher odds of menstrual alterations (aOR: 1.34, 95% CI, 1.15-1.57). In participants with no history of COVID-19, the risk for self-reported menstrual alterations was significantly higher based on employment situation, among participants experiencing financial issues (eg, financial issues always/many times < 12 months: aOR: 1.68, 95% CI, 1.48– 1.90), poorer self-perceived health (eg, poor: aOR: 2.00, 95% CI, 1.31– 3.07), and those diagnosed with polycystic ovary syndrome (aOR: 1.13, 95% CI, 1.02– 1.26). Among participants with a self-reported COVID-19 diagnosis, factors that significantly increased the odds for menstrual alterations were experiencing financial strains (eg, financial issues always/many times < 12 months: aOR: 1.53, 95% CI, 1.09– 2.14), poorer self-perceived health (eg, poor: aOR: 3.09, 95% CI, 1.01– 9.52). Overall, factors that decreased the odds of reporting menstrual alterations included age > 25, being a carer, not having a gynecological condition and using hormonal contraception.Discussion and conclusions: Findings suggest an impact of the COVID-19 syndemic on menstrual patterns. Social inequities in reporting menstrual alterations were identified. While the risk of reporting menstrual alterations was higher among participants with long COVID-19, evidence is not conclusive. Further research on menstrual health in the context of COVID-19 is needed, also to inform policy and practice.Keywords: menstruation, COVID-19, long COVID-19, menstrual health, menstrual inequity, women’s health

Background Menstrual products are necessary goods for women and people who menstruate to manage menstruation. Understanding the use and perceptions of menstrual products is key to promote menstrual equity and menstrual health. This study aimed at assessing the use and perceptions on menstrual products among women and people who menstruate aged 18–55 in Spain. Methods A mixed-methods study was conducted, including a cross-sectional study (N = 22,823), and a qualitative study (N = 34). Results Participants used a combination of products. Non-reusable products were the most used, while over half used reusable products. Usage changed when data were stratified by age, gender identification, completed education, country of birth and experiencing financial issues. It also varied between trans and cis participants. Menstrual products’ use also shifted based on experiences of menstrual poverty and access to information and products. Overall, reusable products were perceived to be more acceptable than non-reusable. Barriers to use the menstrual cup were also identified, including experiences of menstrual inequity (e.g., menstrual poverty, lack of access to information or menstrual management facilities). Conclusion Perceptions and choices of menstrual products need to be acknowledged, especially when designing and implementing menstrual policies to address menstrual inequity and menstrual health.

Gestational diabetes (GD) occurs in 5.8% to 25.1% of pregnant women. This disorder has been linked with intrauterine growth delays, congenital anomalies, and neurobehavioral disorders following birth. As to ophthalmological effects, changes in macular thickness and hypoplasia of the upper quadrant of the papilla have been described. To investigate whether GD has an effect on ophthalmological development in the children born of mothers with this condition. Observational study carried out in children seen in the ophthalmological outpatient clinic of a pediatric hospital in Barcelona (Spain) between January 2011 and December 2015. Participants were ultimately divided into two groups, a study group whose mothers had GD managed either by insulin or diet (GD group) and a control group of children with non-diabetic mothers. Pregestational diabetes cases, were excluded. Complete information was collected on the children’s refraction status, ophthalmological disease, and congenital malformations. Data were compiled on 350 children (229 children born of mothers with GD-186 managed with diet vs 43, with insulin- and 121 controls). The prevalence of amblyopia and strabismus was similar between the groups, but children of mothers with GD had a three-fold greater probability of having refractive errors than children born to mothers without GD. Hyperopia (14.8% vs. 7.4%) and myopia (3.5% vs 0%) were found to be significantly more prevalent in children born of mothers with GD than in the controls (p = 0.027 in both groups).The prevalence of astigmatism was similar in both groups (1.7% vs 0.8%). Refractive errors are more common in children born of mothers with GD. These conditions are easily managed, but if they are not detected, they can lead to amblyopia or accommodative strabismus, interfere with acquisition of fine motor skills, and lead to learning problems. Regular ocular examinations would be recommended in these patients.

IntroductionThe importance of menstrual health has been historically neglected, mostly due to taboos and misconceptions around menstruation and androcentrism within health knowledge and health systems around the world. There has also been a lack of attention on ‘period poverty’, which refers to the financial, social, cultural and political barriers to access menstrual products and education. The main aim of this research is to explore menstrual health and experiences of period poverty among young people who menstruate (YPM).Methods and analysisThis is a convergent mixed-methods study, which will combine a quantitative transversal study to identify the prevalence of period poverty among YPM (11–16 years old), and a qualitative study that will focus on exploring menstruation-related experiences of YPM and other groups (young people who do not menstruate (YNM); primary healthcare professionals; educators and policy-makers). The study will be conducted in the Barcelona metropolitan area between 2020 and 2021. Eighteen schools and 871 YPM will be recruited for the quantitative study. Sixty-five YPM will participate in the qualitative study. Forty-five YNM and 12 professionals will also be recruited to take part in the qualitative study. Socioeconomic and cultural diversity will be main vectors for recruitment, to ensure the findings are representative to the social and cultural context. Descriptive statistics will be performed for each variable to identify asymmetric distributions and differences among groups will be evaluated. Thematic analysis will be used for qualitative data analysesEthics and disseminationSeveral ethical issues have been considered, especially as this study includes the participation of underage participants. The study has received ethical approval by the IDIAPJGol Research Ethics Committee (19/178 P). Research findings will be disseminated to key audiences, such as YPM, YNM, parents/legal tutors, health professionals, educators, youth (and other relevant) organisations, general community members, stakeholders and policy-makers, and academia.

A sensitive, multi-residue method using solid-phase extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed to determine a representative group of 35 analytes, including corrosion inhibitors, pesticides and pharmaceuticals such as analgesic and anti-inflammatory drugs, five iodinated contrast media, β-blockers and some of their metabolites and transformation products in water samples. Few other methods are capable of determining such a broad range of contrast media together with other analytes. We studied the parameters affecting the extraction of the target analytes, including sorbent selection and extraction conditions, their chromatographic separation (mobile phase composition and column) and detection conditions using two ionisation sources: electrospray ionisation (ESI) and atmospheric pressure chemical ionisation (APCI). In order to correct matrix effects, a total of 20 surrogate/internal standards were used. ESI was found to have better sensitivity than APCI. Recoveries ranging from 79 to 134 % for tap water and 66 to 144 % for surface water were obtained. Intra-day precision, calculated as relative standard deviation, was below 34 % for tap water and below 21 % for surface water, groundwater and effluent wastewater. Method quantification limits (MQL) were in the low ng L−1 range, except for the contrast agents iomeprol, amidotrizoic acid and iohexol (22, 25.5 and 17.9 ng L−1, respectively). Finally, the method was applied to the analysis of 56 real water samples as part of the validation procedure. All of the compounds were detected in at least some of the water samples analysed This study was financed by the SpanishMinistry of Science and Innovation through projects CTM2011-28765-C02-02 and CGL2013-48802-C3-2-R, and an FPI grant (Ref. BES-2009-024892) awarded to C. Valls-Cantenys

Aims: The aim of this study was to determine if maternal nutritional status, as defined by body composition, leptin, and insulin-like growth factor (IGF)-I levels, relates to foetal growth. Methods: In this prospective study, mothers of foetuses with foetal growth restriction (FGR; cases; n = 46) and mothers of appropriate-for-gestational-age (AGA) foetuses (controls; n = 81) were consecutively recruited over a 14- month period. A maternal blood sample was obtained during the third trimester (between 32 and 34 weeks of gestation) for the assessment of IGF-I and leptin. Body composition was assessed by dual-energy X-ray absorptiometry within the first 15 days after delivery. The study used the SPSS-PC statistical package, version 19.0, and p < 0.05 was considered statistically significant. Results: Mean serum IGF-I levels were lower in the cases than in the controls (p < 0.05), whereas leptin concentrations were higher in the cases after adjusting for age, body mass index and cigarette consumption (p < 0.05). Cases had less lean and fat tissue than controls (p < 0.05) but a relatively higher fat percentage. Conclusions: The mothers of foetuses with FGR have a body composition pattern characterized by a slightly increased fraction of fat mass, lower IGF-I concentrations, and increased serum leptin levels. Optimization of maternal nutritional status should be considered, as the nutritional status may be involved in the pathogenesis of FGR.

Simple, precise, and low-cost methods for the simultaneous determination of phenolic endocrine disrupting compounds such as bisphenol A, trichlorophenol, pentachlorophenol, 4-nonylphenol, and 4-octylphenol in water samples were developed. The Direct, in situ derivatization methods are based on polydimethylsiloxane rod extraction followed by liquid desorption and chromatographic analysis by liquid chromatography and diode array detection. Several parameters affecting the extraction and desorption of the phenolic compounds and their acetylated derivates were studied, as well as the chromatographic and detection conditions. For the direct method, determination coefficients (r2) > 0.990 and LODs in the 0.6–2 μg/L range were obtained for all compounds except bisphenol A (9.5 μg/L). With the derivatization-based method, based on in situ acetylation, lower limits of detection (0.3–0.9 μg/L) were obtained for all the compounds with r2 > 0.988 and RSDs in the 2–9% range. The developed methods were applied to the analysis of spiked water samples obtaining recoveries of between 60.2 and 131.7% for the direct method, and of between 76.6 and 108.2% for the derivatization-based method. The results demonstrate the feasibility of using these two methods for determining bisphenol A, trichlorophenol, pentachlorophenol, 4-nonylphenol, and 4-octylphenol in water.

This study presents the development and validation of a new analytical method for the simultaneous determination of fifteen analytes classified as halogenated flame retardants (HFRs) – nine brominated diphenyl ethers (BDEs) and six novel HFRs – in different kinds of mollusks using matrix solid-phase dispersion (MSPD) followed by gas chromatography coupled to negative chemical ionization-mass spectrometry (GC–NCI-MS). The proposed method is the first one developed for such a broad range of HFRs in aquatic biota, featuring several advantages, including low solvent and sample intake, simplicity of operation, reduced cost and integration of extraction and clean-up into a single step. Under optimal conditions, 0.5 g of freeze-dried sample, 0.5 g of a primary-secondary amine (PSA) as solid support, a sorbent combination of 1.75 g of florisil (deactivated with 5% Milli-Q water), 1.75 g of acidified silica (10% (w/w) H2SO4) and 0.5 g of silica, and 10 mL dichloromethane as elution solvent were used. Standard addition over the extract was required however for the correct quantification due to matrix effects in the GC system, particularly for novel HFRs, that could not be compensated with the internal standards. The method afforded LODs in the range of 0.003–0.07 ng g−1 dry weight (0.0006–0.014 ng g−1 on a wet weight basis, assuming an 80% sample water content), except for decabromodiphenyl ethane (DBDPE) (0.6 ng g−1 dry weight, 0.12 ng g−1 wet weight). The accuracy of the method was evaluated with three different types of spiked mollusk species using surrogate standards and standard addition over the extract for quantification and the recoveries were in the 70–120% range, except for bis(2-ethylhexyl)-3,4,5,6-tetrabromo-phthalate (DEHTBP) in clam (Ruditapes philippinarum) samples (46% recovery). Moreover, the method was successfully validated with standard reference materials (SRMs) of salmon and mussel tissues for BDEs. Finally, the method was applied to the determination of HFRs in different kind of freeze-dried mollusks: mussel (Mytilus galloprovincialis), cockle (Cerastoderma edule) and clam (R. philippinarum). Raft cultured mussels showed the highest concentrations of HFRs (up to 0.8 ng g−1 wet weight of BDE-209).

Women remained invisible in health sciences until the late twentieth century because they were not included in the cohorts used in researched studies. Thanks to the work done by different groups of feminist researchers, we were able to visualise the need to change those paradigms. But while gender perspectives have allowed us to research new aspects of science, gender has sometimes contributed to rendering female-specific health issues as invisible. For women to be treated equally, their differences have to be recognised, precisely so that the equal right of both sexes to quality of life can be defended. Therefore, the science of difference should be included in research and taught in all health science specialisations.

La ciencia medica no ha tenido en cuenta hasta finales del siglo XX que existen diferencias en el modo de enfermar y en el tipo de enfermedades mas frecuentes entre mujeres y hombres. Existen sesgos de genero en la escasa valoracion de las diferencias tanto biologicas, como psicologicas y sociales. Nuestro grupo ha definido el termino “morbilidad femenina diferencial” para describir y visibilizar estas diferencias. Los factores de riesgo diferenciales destacables para la mortalidad prematura diferencial son los problemas cardiovasculares, el cancer de mama y el de colon. En cuanto a la morbilidad, la menstruacion y sus trastornos es el primer factor diferencial por edad, y las enfermedades endocrinas y el dolor osteomuscular los que causan los problemas mas prevalentes. Tambien son importantes la deficiencia de hierro y las carencias de vitamina D.

Context: The sequence of prenatal growth restraint and infantile catch-up of weight is by the age of 4 yr associated with hyperinsulinemic adiposity. We studied whether the adiposity of post-catch-up children born small for gestational age (SGA) is further amplified between age 4 and 6 yr and whether visceral fat excess has already emerged by the age of 6 yr. Setting: The study took place at a university hospital. Study Population and Design: A longitudinal cohort (age 2–6 yr) of 22 children born appropriate for gestational age (AGA) and 29 born SGA were studied. Auxological, endocrine, metabolic, and body composition (by absorptiometry) assessments were made at 2, 4, and 6 yr, and visceral fat was assessed (by magnetic resonance imaging) at 6 yr. Main Outcomes: Outcome measures included fasting glucose, insulin, IGF-I, neutrophil to lymphocyte ratio, lean mass, and total, abdominal, and visceral fat mass. Results: Between ages 4–6 yr, the relative adiposity of SGA children was further amplified. Between ages 2–6 yr, SGA children gained more total and abdominal fat and raised their insulin, IGF-I, and neutrophil to lymphocyte ratio more than did AGA children (all P < 0.0001). At age 6 yr, the average amount of visceral fat was in SGA children more than 50% higher than in AGA children (P < 0.005). The 0- to 2-yr increment in weight Z-score together with the 2- to 6-yr increment in fasting insulin accounted for 62% of visceral fat variability at age 6 yr. Conclusion: The amount of visceral fat is in post-catch-up SGA children excessive by the age of 6 yr. In populations at risk for type 2 diabetes or metabolic syndrome after fetal growth restraint, the time window for early intervention may have to be advanced into prepubertal childhood.

The design and analysis of research may cause systematic gender dependent errors to be produced in results because of gender insensitivity or androcentrism. Gender bias in research could be defined as a systematically erroneous gender dependent approach related to social construct, which incorrectly regards women and men as similar/different. Most gender bias can be found in the context of discovery (development of hypotheses), but it has also been found in the context of justification (methodological process), which must be improved. In fact, one of the main effects of gender bias in research is partial or incorrect knowledge in the results, which are systematically different from the real values.This paper discusses some forms of conceptual and methodological bias that may affect women’s health. It proposes a framework to analyse gender bias in the design and analysis of research carried out on women’s and men’s health problems, and on specific women’s health issues.Using examples, the framework aims to show the different theoretical perspectives in a social or clinical research context where forms of selection, measurement and confounding bias are produced as a result of gender insensitivity. Finally, this paper underlines the importance of re-examining results so that they may be reinterpreted to produce new gender based knowledge. Spanish Research Network on Health and Gender (RISG)

Summary Background and aim Low-dose pioglitazone (Pio), flutamide (Flu), metformin (Met) plus an oestro-progestagen is a novel polytherapy lowering total and visceral adiposity, and reducing carotid intima media thickness (IMT) in hyperinsulinaemic women with androgen excess, without changing their body mass index (BMI). In a search for mediators of PioFluMet's actions, we measured serum levels of visfatin and high molecular weight (HMW) adiponectin. Design and patients In a double-blind study, we enrolled 38 young women with hyperinsulinaemic androgen excess [mean BMI: 23·7 kg/m2], all of whom started on Flu (62·5 mg/day), Met (850 mg/day) and a transdermal oestro-progestagen, each for 21/28 days over 1 year. Patients were randomly assigned to receive, in addition, placebo (n = 19) or Pio (7·5 mg/day; n = 19) on the same 21/28 days. Measurements Serum concentrations of visfatin and HMW adiponectin, visceral fat by magnetic resonance imaging, carotid IMT by ultrasound, all carried out during study start and after 1 year. Results PioFluMet raised visfatin by a mean 84% and HMW adiponectin by 157% (P

One of the treatments for hyperinsulinemic hyperandrogenism in nonobese women is combined androgen receptor blockade (with flutamide; Flu), insulin sensitization (with metformin; Met) plus an estroprogestagen contraceptive. We tested whether adding low-dose pioglitazone (Pio; 7.5 mg/d) confers more benefit.The study was conducted at a university hospital.This double-blind study enrolled 38 young women with hyperinsulinemic hyperandrogenism [mean body mass index (BMI) 24 kg/m(2)], all of whom started on Flu (62.5 mg/d) and Met (850 mg/d) plus a transdermal estroprogestagen, each for 21 of 28 d over 6 months. Patients were randomly assigned to receive, in addition, placebo (n=19) or Pio (n=19; 7.5 mg/d) for the same 21 of 28 d over 6 months.BMI, waist to hip ratio, hirsutism score, fasting endocrine-metabolic markers, body composition, abdominal fat (visceral vs. sc), and carotid intima-media thickness were measured at study start and after 6 months.PioFluMet reduced intima-media thickness more than FluMet and lowered glucose, IGF-I, and C-reactive protein more as well as the ratio of low-density lipoprotein to high-density lipoprotein cholesterol and the ratio of neutrophils to lymphocytes. PioFluMet treatment was followed by a leaner body composition and a loss of visceral fat (both P0.001). In the total group, the changes included not only decreases in waist to hip ratio, hirsutism score, and testosterone (all P0.001) but also minor drops in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and lactate dehydrogenase (all P0.005), indicating absence of hepatotoxicity; BMI remained unchanged. Clinical side effects were not detected.In this proof-of-concept study, addition of Pio to FluMet plus an estroprogestagen led to improvements in the endocrine-metabolic condition, in low-grade inflammation, in total and visceral adiposity, and in markers of cardiovascular health.

Summary Objective Variation in the tumour necrosis factor gene, (TNF) has been associated with insulin resistance traits. We questioned whether the TNF−308G/A polymorphism is associated with birthweight and insulin resistance in children born small for gestational age (SGA), a patient population known to be at risk for insulin resistance. Design A cross-sectional, hospital-based study assessing insulin sensitivity in SGA children. Patients One hundred and ninety-eight school-age children born either SGA (n = 90, age 7·4 ± 4·5 years) or appropriate for gestational age (AGA, n = 108, age 8·7 ± 4·0 years). Measurements All children were genotyped for the TNF−308G/A polymorphism; a biochemical profile was also performed in prepubertal SGA (n = 58) and AGA (n = 57) subjects. Results Genotype frequencies for the TNF−308G/A single nucleotide polymorphisms (SNPs) (GG and GA/AA) differed between SGA and AGA children (86%vs. 72% and 14%vs. 28%, respectively; P = 0·025). The GG genotype was associated with lower birthweight and birth length (2747·0 ± 23·3 g vs. 2851·0 ± 45·7 g, P = 0·045, and 47·0 ± 0·2 cm vs. 48·2 ± 0·4 cm, P = 0·011, respectively) and, in AGA but not in SGA children, with higher systolic blood pressure [103·3 (95% confidence interval (CI) 96·4–110·2) mmHg vs. 92·8 (84·9–100·7) mmHg; P = 0·028], higher blood glucose [4·8 (4·7–5·0) mmol/l vs. 4·5 (4·3–4·8) mmol/l; P = 0·042] and higher homeostasis model assessment for insulin resistance (HOMA-IR) index [1·4 (1·1–1·7) vs. 0·9 (0·4–1·3); P = 0·005]. In multivariate analysis, the TNF−308GG genotype was an independent predictor of HOMA-IR during childhood, explaining 8% of its variance. Conclusion SGA children show increased frequency of the TNF−308G allele, an allele that is associated with prenatal growth and with postnatal insulin resistance. The TNF−308G/A polymorphism may have implications in the growth and metabolic abnormalities that characterise SGA children.

To evaluate deoxypyridinoline as a resorption marker in phenylketonuria (PKU) and to search for a relationship between deoxypyridinoline, calcium/creatinine index (Ca/Cr I), osteocalcin and bone alkaline phosphatase (BAP).This was a transversal analytical study of 46 PKU patients [17.5 (4-38) years]. Deoxypyridinoline and osteocalcin were measured with a chemiluminescent assay and BAP was measured with an immunoradiometric assay.Deoxypyridinoline was significantly increased in patients aged 7-14 and18 years old, being associated with age (r=-0.724, P0.001). Adult patients showed significantly higher Ca/Cr I, which correlates with Phe values for the year prior to the study (P=0.014). Serum BAP was significantly increased in pediatric patients (9-13 years), while it was decreased in adult patients (P=0.003). Decreased osteocalcin levels were found in patients15 years (P=0.028). Altered deoxypyridinoline and BAP values were related (P=0.042).PKU patients excreted increased D-Pyr, suggesting high bone resorption. Bone formation seems active in childhood but deteriorates in adult PKU patients. Periodic measurement of D-Pyr and BAP may be useful in the prevention of osteopenia in PKU patients.

Low-dose flutamide-metformin (Flu-Met) with an oral contraceptive is a therapeutic option for women with hyperinsulinaemic hyperandrogenism. We questioned (i) whether Flu-Met maintains efficacy if given discontinuously; (ii) how the efficacy of discontinuous Flu-Met plus a transdermal contraceptive compares with Flu-Met plus oral contraceptive; and (iii) whether these treatments also lower circulating C-reactive protein (CRP) and tumour necrosis factor alpha (TNF-alpha) and the high neutrophil/lymphocyte ratio.Non-obese, young patients (n = 31) with hyperinsulinaemic hyperandrogenism were started on Flu-Met (21/28 days) and randomized to receive in addition either a drospirenone oral contraceptive or a transdermal contraceptive for 6 months.The effects of Flu-Met were similar whether combined with oral or transdermal contraceptive. In both groups, CRP and TNF-alpha levels fell and the high neutrophil/lymphocyte ratio normalized (P0.001). Lean body mass increased (P0.001) in both groups but, in contrast to earlier experience with continuous Flu-Met, fat mass failed to decrease in either group.Flu-Met seems less lipolytic, if given for only 21 days in every 28-day period. The efficacy of Flu-Met is comparable when combined with an oral contraceptive or a transdermal contraceptive. The range of Flu-Met effects may henceforth include lower levels of CRP and TNF-alpha, and a normalization of the neutrophil/lymphocyte ratio.

A minority of children born small for gestational age (SGA) maintain a slow weight gain and a short stature (SS). At the other end of the spectrum are SGA children who show rapid postnatal weight gain and catch-up growth; these subjects may develop hyperinsulinemia, exaggerated adrenarche with precocious pubarche (PP), and an associated proinflammatory state with raised IL-6 and reduced adiponectin levels. Metformin therapy in SGA-PP girls attenuates the hyperinsulinemia, the adrenal androgen excess, and the proinflammatory state. In contrast, GH therapy in SGA-SS children promotes height gain but may induce hyperinsulinemia. Both groups are associated with increased risk markers for future cardiovascular disease. Therefore, we studied markers of inflammation in both SGA subpopulations at baseline and after their respectively corrective therapies. SGA-PP girls (n = 33; mean age, 8 yr; body mass index, 18.5 kg/m(2)) were randomized to remain untreated or to receive metformin (425 mg/d) for 6 months. SGA-SS children (n = 29; mean age, 7 yr; body mass index, 14.7 kg/m(2)) were randomly assigned to remain untreated or to receive GH (60 mug/kg/d). In SGA-PP girls, the mean neutrophil count (4.0 x 1000/mm(3)) was more than 2 sd above the mean reference level (2.8 x 1000/mm(3), P < 0.001); this remained stable over 6 months in untreated girls but dropped in metformin-treated girls by -1.1 x 1000/mm(3) (P = 0.002). In SGA-SS children, neutrophil counts were also higher at baseline (3.3 x 1000/mm(3), P < 0.01). This remained stable in untreated children but rose in GH-treated children by +1.1 x 1000/mm(3) (P = 0.004). GH-treated children also showed a rise in circulating IL-6 and dehydroepiandrosterone-sulfate levels and a fall in adiponectin levels. In conclusion, neutrophil counts were elevated in SGA children. In SGA girls with PP, the present results corroborate the antiinflammatory benefits of metformin therapy. In contrast, high-dose GH therapy in short SGA children may increase neutrophil counts and lead to a less favorable adipocytokine profile. Future studies with combined GH plus metformin treatment in short SGA children may clarify whether insulin resistance is a mechanism linking GH therapy to markers of inflammation.

A low-dose combination of flutamide-metformin and ethinylestradiol-drospirenone was recently found to reduce the excess of total and abdominal fat, to diminish the deficit in lean mass, and to attenuate the dysadipocytokinemia of young women with ovarian hyperandrogenism, a variant of polycystic ovary syndrome. We questioned the need to give flutamide, an androgen receptor blocker, together with an oral contraceptive that contains drospirenone, a progestin claimed to have antiandrogen properties. The additive effects of low-dose flutamide (62.5 mg/d) were assessed over 3 months in young patients with hyperinsulinemic ovarian hyperandrogenism (n = 40; age, approximately 17 yr; body mass index, approximately 22 kg/m(2)); all participants started on metformin (850 mg/d) and a fourth-generation contraceptive (ethinylestradiol 30 microg plus drospirenone 3 mg, 21 d/month), and they were randomized to receive flutamide in addition (n = 20) or not (n = 20). Fasting blood glucose, serum insulin, lipid profile, testosterone, adiponectin, and IL-6 were determined at baseline and after 3 months, together with body composition (by dual x-ray absorptiometry) and with Doppler assessment of ovarian arterial resistance. At start, the pulsatility and resistance indices of ovarian arteries were elevated. By comparison of 3-month changes between randomized subgroups, the addition of low-dose flutamide was found to have consistently (more) normalizing effects on low-density lipoprotein cholesterol, IL-6, and adiponectin, lean body mass, total and abdominal fat mass, and arterial flow in the ovaries. In conclusion, low-dose flutamide is herewith identified as a pivotal component within a first contraceptive combination therapy that has been shown to attenuate the hypoadiponectinemia, ovarian vascular hyperresistance, lean mass deficit, and central adiposity of young women with polycystic ovary syndrome. Finally, these data challenge any claim that drospirenone, as currently used in a contraceptive, is a clinically significant antiandrogen.

Among girls with precocious pubarche (PP), those with low birth weight (LBW) are, even if nonobese, at risk for progression to polycystic ovary syndrome (PCOS) including hyperinsulinemic hyperandrogenism, dyslipidemia, dysadipocytokinemia, and central fat excess. Recently, we disclosed the efficacy of insulin sensitization with metformin to disrupt progression from PP to PCOS in formerly LBW girls who were postmenarche. In LBW-PP girls, we have now extended the exploration of early insulin sensitization therapy in two directions: 1) metformin therapy was started before puberty; and 2) we assessed the effects of metformin discontinuation in girls who had started metformin treatment after menarche. Prepubertal LBW-PP girls (n = 33; mean age, 8.0 yr; body mass index, 18.5 kg/m(2)) were randomly assigned to remain untreated or to receive metformin (425 mg/d) for 6 months. Postpubertal LBW-PP girls (n = 24; age, 12.4 yr; body mass index, 21.0 kg/m(2)) had been randomized (at -12 months) to remain untreated or to receive metformin (850 mg/d) for 12 months, at which time (0 month) a treatment cross-over was performed for 6 months. Fasting blood glucose and serum insulin, SHBG, dehydroepiandrosterone sulfate, androstenedione, testosterone, lipid profile, IL-6, and adiponectin were assessed at 0 and 6 months, as was body composition (by dual x-ray absorptiometry). In the prepubertal study (group A), comparisons of untreated vs. treated girls disclosed normalizing effects of metformin on SHBG, androstenedione, dehydroepiandrosterone sulfate, low and high density lipoprotein cholesterol, triglycerides, IL-6, adiponectin, total and abdominal fat mass, and lean body mass. In the postpubertal study (group B), treatment cross-over at 0 month was in each subgroup followed by a striking reversal in the course of the endocrine-metabolic state, adipocytokinemia, and body composition; all changes pointed to normalizing effects of metformin treatment. In conclusion, these two studies provide the first evidence that 1) prepubertal metformin therapy has normalizing effects on PCOS features in high risk girls with a combined history of LBW and PP; and 2) in adolescence, metformin's normalizing effects are reversed as soon as metformin therapy is discontinued.

Resumen Objetivo Comprender las actitudes, comportamientos, creencias y conocimiento de la enfermedad en las personas diagnosticadas de diabetes tipo 2, asi como comprender que esperan de los profesionales sanitarios respecto al soporte y ayuda en el control de su enfermedad Diseno Estudio cualitativo, con un diseno interpretativo de tipo hermeneutico Emplazamiento La investigacion fue realizada en el primer semestre del ano 2001 y la poblacion estudiada procedia de Sabadell, poblacion urbana de la provincia de Barcelona Participantes Un total de 21 pacientes diagnosticados de diabetes tipo 2, atendidos en centros de atencion primaria Metodo Analisis de contenido de 21 entrevistas semiestructuradas realizadas en el domicilio. La validez del analisis fue asegurada mediante su revision por varios miembros del equipo investigador Resultados La diabetes es una enfermedad socialmente aceptada. Los pacientes se sienten mas o menos diabeticos segun sean tratados o no con insulina. La perdida que consideran mas importante es no poder comer ciertas cosas. Los diabeticos diferencian entre los conocimientos que ellos necesitan y los que han de tener los profesionales. El principal apoyo del diabetico es la familia, seguido del de los profesionales sanitarios Conclusiones os planes educativos han de ir muy relacionados con las demandas reales de las personas diabeticas. Estas esperan de los profesionales sanitarios, ademas de los conocimientos propios de la enfermedad, ser atendidas con valores eticos y de apoyo

The endocrine-metabolic hallmarks of polycystic ovary syndrome are hyperinsulinism, hyperandrogenism, dyslipidemia, and anovulation. We hypothesized that dyslipidemia and anovulation in nonobese women with polycystic ovary syndrome are essentially secondary to the concerted effects of hyperandrogenism and insulin resistance. We tested this hypothesis by comparing the efficacy of anti-androgen (flutamide) or insulin-sensitizing (metformin) monotherapy to that of combined therapy in normalizing the endocrine-metabolic and anovulatory status of nonobese, young women with hyperinsulinemic hyperandrogenism. Thirty-one young women (mean age, 18.7 yr; body mass index, 21.9 kg/m(2); hirsutism score, 16; monthly ovulation rate monitored by weekly serum progesterone, 10%) were randomly assigned to receive once daily flutamide (250 mg; n = 10), metformin (1275 mg; n = 8), or combined flutamide- metformin therapy (n = 13) for 9 months. At baseline, there were no endocrine-metabolic differences among treatment groups. Compared with monotherapy, combined flutamide-metformin therapy resulted in greater improvements in insulin sensitivity, in testosterone, androstenedione, dehydroepiandrosterone sulfate, and triglyceride levels, and in low-density lipoprotein/high-density lipoprotein-cholesterol ratio (all P < 0.005). Monthly ovulation rates increased after 9 months to 75 and 92%, respectively, with metformin alone or with combined therapy, but were unimproved with flutamide alone. All treatments were well tolerated. In conclusion, combined anti-androgen and insulin-sensitizing treatment in young, nonobese women with hyperinsulinemic hyperandrogenism had additive benefits on insulin sensitivity, hyperandrogenemia, and dyslipidemia. The data from this small study suggest that dyslipidemia is secondary to excess androgen action in concert with the hyperinsulinemia associated with insulin resistance. In contrast, anovulation seems to be mainly attributable to insulin resistance and hyperinsulinemia.

Simple, precise, and low-cost methods for the simultaneous determination of phenolic endocrine disrupting compounds such as bisphenol A, trichlorophenol, pentachlorophenol, 4-nonylphenol, and 4-octylphenol in water samples were developed. The Direct, in situ derivatization methods are based on polydimethylsiloxane rod extraction followed by liquid desorption and chromatographic analysis by liquid chromatography and diode array detection. Several parameters affecting the extraction and desorption of the phenolic compounds and their acetylated derivates were studied, as well as the chromatographic and detection conditions. For the direct method, determination coefficients (r(2) )0.990 and LODs in the 0.6-2 μg/L range were obtained for all compounds except bisphenol A (9.5 μg/L). With the derivatization-based method, based on in situ acetylation, lower limits of detection (0.3-0.9 μg/L) were obtained for all the compounds with r(2)0.988 and RSDs in the 2-9% range. The developed methods were applied to the analysis of spiked water samples obtaining recoveries of between 60.2 and 131.7% for the direct method, and of between 76.6 and 108.2% for the derivatization-based method. The results demonstrate the feasibility of using these two methods for determining bisphenol A, trichlorophenol, pentachlorophenol, 4-nonylphenol, and 4-octylphenol in water.

BACKGROUND Our aim was the detection of possible deficiencies of folate and cobalamin by the measurement of plasma total homocysteine (tHcy) in 69 human immunodeficiency virus (HIV) -infected children on antiretroviral treatment. We studied the relationship of these vitamins and methionine with tHcy values. MATERIALS AND METHODS Plasma tHcy was determined by high-performance liquid chromatography with fluorescence detection, folate and cobalamin by competitive protein-binding chemiluminescence, and methionine by ion exchange chromatography. RESULTS Significant differences were observed between tHcy concentrations in the HIV-infected patients and the reference values for children of similar ages (P < 0.0001). Folate values were significantly lower in HIV-infected children compared with our reference paediatric population (P < 0.0001), but cobalamin concentrations were similar between patients and reference values. A significantly negative correlation was found between tHcy and folate (r = - 0.596; P < 0.0001), and a significantly positive correlation between folate and the methionine : tHcy ratio (r = 0.501; P < 0.0001). Plasma tHcy was significantly higher (P = 0.008), while folate values and methionine : tHcy ratios were significantly lower (P = 0.007 and P = 0.042), in patients on protease inhibitor treatment than in patients on other antiretroviral therapies. CONCLUSIONS The hyperhomocysteinaemia and low methionine : tHcy ratios observed in our group of HIV-infected children are probably a consequence of the low folate values, which interfere in the remethylation of homocysteine to methionine. Patients on protease inhibitor treatment showed significantly higher plasma tHcy concentrations, and lower folate values and methionine : tHcy ratios, compared with patients on other antiretroviral therapies. Hyperhomocysteinaemia is associated with the risk of premature stroke, which may have adverse consequences in the evolution of disease.

OBJECTIVE Young girls with precocious pubarche (PP) are at increased risk of developing polycystic ovary syndrome (PCOS), including hyperinsulinism, dyslipidaemia and ovarian hyperandrogenism, particularly if PP itself was preceded by a low birthweight. Resistance to insulin is thought to be a key factor in the pathogenesis of this sequence. We aimed to elucidate the peripubertal ontogeny of the low birthweight effect on hyperinsulinism, dyslipidaemia and ovarian dysfunction after PP. PATIENTS AND DESIGN We obtained fully longitudinal data from 51 girls with a history of PP and compared normal-birthweight (n = 26) with low-birthweight (n = 25) girls (birthweight SD score 0·0 ± 0·2 vs. − 2·4 ± 0·2) for measurements obtained at diagnosis of PP (mean age 7·0 years), in early puberty (10·4 years) and after menarche (14·3 years). MEASUREMENTS Fasting serum lipids and lipoproteins, together with insulin responses to an oral glucose load, were assessed at diagnosis of PP, in early puberty and after menarche; serum gonadotropins were measured in early puberty and after menarche; ovarian function was examined postmenarche. RESULTS Comparisons of endocrine-metabolic results between normal- and low-birthweight PP girls showed no detectable differences before puberty. The hypertriglyceridaemia and elevated LDL-cholesterol levels characterizing low-birthweight PP girls became detectable by early puberty; reduced insulin sensitivity was not evident until postmenarche, when the tendency to ovarian dysfunction also became obvious. Body mass indices of normal- and low-birthweight subgroups were identical in early puberty and postmenarche. CONCLUSIONS These longitudinal data show that, in PP girls, the endocrine-metabolic risk conferred by prenatal growth restraint is not readily detectable until puberty or postmenarche, and is not attributable to a higher body mass index.

Even nonobese girls with precocious pubarche may develop a variant of polycystic ovary syndrome (PCOS) characterized by hyperinsulinism, hyperandrogenism, abnormal lipids, and persistent anovulation. Insulin-sensitizing treatment has limited hyperinsulinism and hyperandrogenism and restored eumenorrhea in women with PCOS. Extrapolating from observations in obese women with PCOS who receive an insulin-sensitizing agent such as metformin or troglitazone and become more likely to ovulate, this study examined the effects of metformin in 18 nonobese adolescent girls with a mean age of 16½ years who were 3 to 7 years past menarche. All were anovulatory and met clinical and hormonal criteria for ovarian hyperandrogenism. The participants also had a history of precocious pubarche caused by exaggerated adrenarche. All the girls were hyperinsulinemic but had normal glucose tolerance. Anovulation was confirmed twice by obtaining four consecutive serum progesterone levels below 4 ng/ml at 1-week intervals. Metformin was given for 6 months in a daily dose of 1275 mg. Hirsutism scores decreased with metformin therapy, as did levels of fasting serum insulin, luteinizing hormone, total testosterone, androstenedione, dehydroepiandrosterone sulfate, and the free androgen index. Serum levels of sex hormone-binding globulin increased at the same time, and the lipid profiles became less atherogenic. There were no changes in body mass index, fasting glycemia, or serum levels of estradiol or follicle-stimulating hormone. All but 2 of the 18 girls reported regular menses within 4 months of the start of metformin therapy and, after 6 months, all were eumenorrheic. Ovulation induction failed in 4 of the 18 girls (Fig. 1), including the 2 with the most severe hyperandrogenism. Abdominal discomfort in 4 girls resolved spontaneously within 2 weeks. Metformin treatment tends to normalize endocrine-metabolic function in nonobese adolescent girls with anovulatory hyperandrogenism and induces ovulation in many of them.