The benefits of co-location in primary care practices: the perspectives of general practitioners and patients in 34 countries.

BACKGROUND: There is no clear evidence as to whether the co-location of primary care professionals in the same facility positively influences their way of working and the quality of healthcare as perceived by patients. The aim of this study was to identify the relationships between general practitioner (GP) co-location with other GPs and/or other professionals and the GP outcomes and patients' experiences. METHODS: We wanted to test whether GP co-location is related to a broader range of services provided, the use of clinical governance tools and inter-professional collaboration, and whether the patients of co-located GPs perceive a better quality of care in terms of accessibility, comprehensiveness and continuity of care with their GPs. The source of data was the QUALICOPC study (Quality and Costs of Primary Care in Europe), which involved surveys of GPs and their patients in 34 countries, mostly in Europe. In order to study the relationships between GP co-location and both GPs' outcomes and patients' experience, multilevel linear regression analysis was carried out. RESULTS: The GP questionnaire was filled in by 7183 GPs and the patient experience questionnaire by 61,931 patients. Being co-located with at least one other professional is the most common situation of the GPs involved in the study. Compared with single-handed GP practices, GP co-location are positively associated with the GP outcomes. Considering the patients' perspective, comprehensiveness of care has the strongest negative relationship of GP co-location of all the dimensions of patient experiences analysed. CONCLUSIONS: The paper highlights that GP mono- and multi-disciplinary co-location is related to positive outcomes at a GP level, such as a broader provision of technical procedures, increased collaboration among different providers and wider coordination with secondary care. However, GP co-location, particularly in a multidisciplinary setting, is related to less positive patient experiences, especially in countries with health systems characterised by a weak primary care structure.

Characterization of circadian COPD symptoms by phenotype: Methodology of the STORICO observational study.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide. The symptoms of COPD are troublesome, variable, can occur during all parts of the 24-h day and have a substantial impact on patients' health status, quality of life and healthcare resource utilization. Reducing symptoms, improving health status and increasing physical activity are major goals in the management of stable COPD. In order to provide effective, patient-oriented care, patients should be evaluated on the basis of lung function, frequency of symptoms and patient-perceived impact of symptoms on their lives and treatment decisions made on a case-by-case basis. The identification of COPD phenotypes is an evolving debate and literature data about the circadian variation of COPD symptoms according to phenotypes are nowadays lacking. The ongoing STORICO (STudio Osservazionale sulla caratteRizzazione dei sIntomi delle 24 ore nei pazienti con BPCO) study (NCT03105999) is aimed to describe by clinically defined phenotypes the frequency and 12-month evolution of early-morning, day- and night-time COPD symptoms in a cohort of 600 Italian patients with stable COPD. Secondary objectives include the description of the 12-month variation of outcomes of interest according to phenotypes and of the healthcare resources utilization (overall and by phenotype) during 12-month observation. An exploratory analysis will be conducted aimed to phenotype COPD patients in an alternative researcher-independent way based on circadian pattern of symptoms combined with measures of respiratory function, health-related quality of life and comorbidity. The present paper describes the methodology of the STORICO study.

The effect of administering gonadotropin-releasing hormone agonist with recombinant-human growth hormone (GH) on the final height of girls with isolated GH deficiency: results from a controlled study.

To assess whether delaying puberty may improve final height in GH-deficient children with a poor height prediction at early puberty, we studied 24 girls with isolated GH deficiency until they reached their final height, in a controlled trial. Patients were taking recombinant human GH (r-hGH) substitutive therapy from 2.1 +/- 0.5 yr (0.1 IU/kg.day sc) before entering the study, without showing any improvement in height prediction (149.6 +/- 2.9 vs.150.3 +/- 2.2 cm) on entering puberty. Fourteen girls agreed to add a GnRH agonist (GnRHa) to r-hGH, whereas the remaining 10 decided against it and served as controls. At the start of the study, girls treated with or without GnRHa had similar auxological characteristics (bone age, 10.9 +/- 0.6 vs. 10.7 +/- 1.3 yr; height SD score for chronological age, -1.87 +/- 0.3 vs. -1.82 +/- 0.2), including pubertal development. The GnRHa (long-acting D-Trp-6-GnRH) was given at 60 microg/kg im every 28 days for 1.9 +/- 0.9 yr, then patients continued the r-hGH at the same dosage (3.1 +/- 0.7 yr). At the end of the study, bone age was 16.2 +/- 0.3 yr in GnRHa-treated girls and 16.6 +/- 0.9 yr in controls. Bone maturation was significantly slower during GnRHa (1.4 +/- 0.2 yr), and height SD score for bone age improved (-0.31 +/- 0.3) in comparison with controls (2.6 +/- 0.4 yr and -1.35 +/- 0.3 SD score; P < 0.001 and P < 0.0001, respectively). As a result, girls given the combined therapy reached a final height higher than that of controls (height SD score, -0.39 +/- 0.5 vs. -1.45 +/- 0.2; P < 0.0001) and also higher than their midparental height (-1.1 +/- 0.5; P < 0.0005). Controls reached their midparental height. In conclusion, our results demonstrate that slowing pubertal development with the administration of GnRHa for a limited time may improve final height in GH-deficient girls selected because of a poor height prediction at early puberty.

The effect of long-term growth hormone (GH) treatment on bone mineral density in children with GH deficiency. Role of GH in the attainment of peak bone mass.

The effect of long-term GH treatment on bone mass was examined in 32 children with GH deficiency (GHD) aged 7.2-16.3 yr by measuring radial (distal third, single-photon absorptiometry) and lumbar (L2-L4, dual energy x-ray absorptiometry) bone mineral density (BMD) (group A). All patients were longitudinally followed and received recombinant hGH therapy for a mean period of 48.2 +/- 13.2 months. BMD values were corrected for bone age and expressed as Z-score in comparison with normative data. In addition, lumbar BMD and lumbar BMD corrected for the estimated vertebral volumes were assessed in 11 patients with GHD aged 16.0 - 18.7 yr at the time they reached their final height (group B) and, in 17 subjects with familial short stature aged 16.4 - 19.8 yr, as controls (group C) for patients of group B. Patients of group B had received discontinuous treatment with pituitary-derived hGH and subsequently recombinant hGH (total duration of treatment 151.5 +/- 9.7 months). The off-treatment period was 4.7 +/- 2.6 months. Before treatment, patients of group A showed significantly reduced (P < 0.001) radial and lumbar BMD (-1.7 +/- 0.4 Z-score and -1.5 +/- 0.5 Z-score, respectively) compared with normative data. During treatment, radial and lumbar BMD Z-scores improved significantly (P < 0.001); in the patients treated for the longest time, the BMD was within 0.5 SD of age-matched mean levels. In patients of group B, lumbar BMD and lumbar BMD corrected for the estimated vertebral volumes were significantly reduced in comparison with subjects of group C (-1.2 +/- 0.4 Z-score and -1.0 +/- 0.4 Z-score, P < 0.01 and P < 0.03, respectively). The results show that children with GHD have reduced BMD. Optimal GH treatment improves BMD, whereas inappropriate treatment is a main cause of reduced BMD at time of final height. These findings suggest an important role of GH therapy in the attainment of peak bone mass in children with GHD. GH treatment should be continued until the attainment of peak bone mass irrespective of the height achieved.

Management of puberty in growth hormone deficient children.

The pubertal growth spurt accounts for approximately one-eighth of adult height and is regulated by complex hormonal interactions involving the somatotropic and gonadal axes. The observation that children with growth hormone deficiency (GHD) may fail to achieve an appropriate pubertal growth spurt led to the development of strategies to optimize GH therapy during puberty. In one strategy the dosage of GH is increased during puberty to support pubertal growth and in keeping with the physiological increase in serum levels of the hormone seen at that age. A different approach is to combine a GnRH analog (GnRHa) to GH to stop pubertal development, delaying epiphyseal fusion and prolonging peripubertal growth. Both strategies require caution. As regards the first strategy, too high doses of GH may shorten the pubertal time for growth; we found a small, nonsignificant, improvement in final height by increasing the dose by less than half. Preliminary results on the second strategy are more encouraging. However, manipulation of puberty should be limited to selected patients who show a statural height SDS for bone age unfavorable in terms of height prognosis.

Is there a place for combined therapy with GnRH agonist plus growth hormone in improving final height in short statured children?

The availability of recombinant human growth hormone (GH) and the optimization of substitutive therapy have improved final growth in children with GH deficiency, but despite this some of them fail to grow to their genetic potential. In particular, this may occur in patients who started the substitutive therapy too late and/or in whom bone age progressed too fast during GH administration. In these patients, with unfavorable auxological characteristics, the administration of a GnRH agonist in combination with GH may slow down bone maturation and prolong prepubertal growth, mimicking, to some extent, the growth pattern of patients with GH + Gn deficiency who grow better than children with isolated GHD. A different condition in which such a combined therapy might be used is the short normal child. As they are short but normally-growing children, the onset of puberty is in general appropriate for their chronological age but precocious for their height age. Thus, slowing down pubertal maturation may increase the time available for growth. GH would sustain growth during both GnRHa administration and after its withdrawal, when puberty starts again. Our preliminary results suggest that the administration of GH + GnRHa in combination may have a positive effect on final height in selected children with isolated GHD and in short normal children.

[Growth hormone treatment of familial hypophosphatemic rickets]. / Traitement par hormone de croissance du rachitisme hypophosphatémique familial.

X-linked hypophosphatemic rickets (XLHR) is frequently associated with growth retardation and short adult stature, even with an appropriate conventional treatment associating phosphate and calcitriol or 1 alpha-hydroxyvitamin D. Its pathogenesis is unclear; growth hormone (GH) secretion is usually normal. Six children with XLHR and growth retardation were treated with GH during 6 years. In addition, they received the conventional treatment. At the beginning of the treatment mean age was 7.8 +/- 1.8 years, and height mean Z score was -3.4 +/- 0.5. A control group was composed of six children with XLHR (age: 7.9 +/- 2.5 years) receiving the conventional treatment only. Under GH treatment statural growth was improved, with significant increase in Z score and predicted adult height; the height gain was significantly higher in the GH treated group as compared with the group receiving the conventional treatment only. In addition, radial bone mineral density increased significantly under GH treatment. GH treatment thus appears to be a useful treatment to improve statural growth in children with XLHR.

Combination treatment with growth hormone and gonadotropin-releasing hormone analogs in short normal girls.

To improve final adult height, we treated with growth hormone (0.65 +/- 0.07 (mean +/- SD) IU.kg-1.wk-1) and gonadotropin-releasing hormone analogs (66 +/- 9 micrograms.kg-1 every 28 days) a group of seven short normal girls in early puberty with a chronologic age (CA) of 11.50 +/- 0.95 years, predicted adult height (PAH) lower (0.003 < p < 0.001) than mean target height, and without any endocrine abnormalities. The results were compared with those obtained in a similar group of seven untreated girls considered as control subjects. The mean period of combined therapy was 2.01 +/- 0.52 years; in two subjects treatment is still in progress. The value of height standard deviation score for bone age (BA) improved from -1.69 +/- 0.47 to -1.04 +/- 0.56 (p = 0.001); height age (HA)/BA ratio also increased from 0.83 +/- 0.05 to 0.90 +/- 0.04 (p < 0.01), as did PAH (from 146.8 +/- 4.4 to 152.9 +/- 3.6 cm; p < 0.002). The ratio of gain in HA to gain in BA was 2.08 +/- 0.78. Pubertal stages showed an arrest in five cases and a regression in the other two girls. After administration of gonadotropin-releasing hormone analogs was interrupted, in four of five girls growth hormone was administered alone for a further period of 6 to 18 months to improve their physiologic growth spurt. The present height in five girls is higher than PAH before therapy. In the treated girls the height values for BA, for BA/CA and HA/BA ratios, and for PAH were higher (0.002 < p < 0.04) than those in control subjects. This preliminary study demonstrates that combination therapy with growth hormone and gonadotropin-releasing hormone analogs in short, endocrinologically normal girls may be useful in improving both height prognosis and predicted adult height. Further studies are necessary to reach definitive conclusions regarding the efficacy of this kind of therapy.