Adherence and long-term outcomes of therapy in paediatric patients in Greece using the easypod™ electromechanical device for growth hormone treatment: The phase IV multicentre easypod™ connect observational study (ECOS).

BACKGROUND: The easypod™ injection device allows automatic recording and transmission of adherence data from patients receiving recombinant human growth hormone (rhGH [Saizen®]) to treat growth disorders. This analysis aimed to evaluate the adherence of Saizen® administered via easypod™ in a cohort of Greek patients from the easypod™ connect observational study (ECOS). METHODS: The phase IV, open-label, multicentre, observational, and longitudinal ECOS study (EMR200104-520, NCT01363674) enrolled patients treated for a minimum of 6 months and up to 3 years. The primary endpoint was to assess the mean rate of adherence to treatment at different time points, where good adherence was defined as ≥85%. Change in height, height standard deviation score (SDS), height velocity and height velocity SDS were evaluated after 1 year of treatment as secondary endpoints, together with the impact of adherence on growth outcomes using the Spearman's product moment. RESULTS: Of the 180 patients enrolled, 86 were included in the analysis. The mean adherence to Saizen®, as recorded via easypod™, was high at each individual time point, and was maintained at 95.5% after 1 year of treatment. Clinically meaningful positive changes were also noted for all of the secondary endpoints (median increase in height = 7.25 cm, height SDS = 0.32, median height velocity = 7.62 cm/year and height velocity SDS = 1.65). However, no significant correlation was noted between adherence and growth outcomes. CONCLUSIONS: rhGH replacement therapy using Saizen® with easypod™ led to full compliance to the treatment in a representative Greek population from ECOS, and provided additional insights on how the easypod™ device can assist physicians in monitoring adherence and help to optimise linear growth in paediatric patients with growth disorders.

Adherence to treatment in children with growth hormone deficiency, small for gestational age and Turner syndrome in Mexico: results of the Easypod™ connect observational study (ECOS).

BACKGROUND: Assessing adherence to growth hormone (GH) is challenging. The Easypod™ connect device delivers pre-set doses of recombinant human GH (r-hGH) and stores a digital record of adherence that can be shared with healthcare provider. We assessed adherence to r-hGH delivered with Easypod™ according to the approved pediatric indications for r-hGH: growth hormone deficiency (GHD), born small for gestational age (SGA) who failed to show catch-up growth and Turner syndrome (TS). METHODS: ECOS (NCT01555528) was a multicenter (24 countries), 5-year, longitudinal, observational study, which aimed to evaluate country-specific adherence to r-hGH therapy prescribed via the Easypod™ electronic injection device. The primary endpoint was yearly adherence. Secondary endpoints were height velocity, height velocity standard deviation scores (SDS), height, height SDS and IGF-1 concentrations. Clinical and auxological data were obtained from medical records and adherence from Easypod™ logs. RESULTS: This study included 147 Easypod™-naïve Mexican children assessed during 3 years (mean age: 9.96 ± 3.41 years, 56.8% boys, mean height SDS at baseline: - 2.17 ± 0.97): 118 with GHD, 24 SGA and 5 with TS. A total of 105 (71.4%) patients were GH naïve. Overall median adherence was > 90% over the first year of treatment and > 80% at 3 years. Adherence was not different by r-hGH indication or between GH-naïve or experienced patients. At 1-year follow-up, mean change in height SDS was 0.57 ± 0.34, whereas mean height velocity SDS was 2.85 ± 2.51. In all, 84.7% patients had normal IGF-1 concentrations at 1-year follow-up. Adherence was associated with change in height SDS (r = 0.239, p = 0.005) and height velocity SDS (r = 0.194, p = 0.027). CONCLUSION: Adherence rates with the Easypod™ device are high and maintained over time in GHD, SGA and TS Easypod™-naïve Mexican patients. High adherence is associated with better outcomes. Easypod™ assists physicians in monitoring adherence to r-hGH.

Bone status and fracture prevalence in Russian adults with childhood-onset growth hormone deficiency.

The consequences of lifelong untreated childhood-onset GH deficiency (COGHD) on adult bone and especially fracture prevalence are largely unknown due to the lack of data on long-term outcome of untreated patients. Therefore, we studied adult Russian patients (n = 66; 28 females and 38 males) with idiopathic GH-untreated COGHD. Patients had isolated GH deficiency (IGHD; n = 18, age 23 +/- 10 yr) or multiple pituitary hormone deficiency (MPHD) with open (OMPHD; n = 27, age 23 +/- 5 yr) or closed growth plates (CMPHD; n = 21, age 55 +/- 12 yr). Bone mineral content (BMC) and bone mineral density (BMD) values were compared with 821 normal Russian controls. Fracture prevalence was ascertained from medical history and compared with similar data from 333 normal controls. Height sd score was -4.6 (range, -1.8 to -8.1). This represents 82% of the height of normal Russian adults. BMC of the lumbar spine, femoral neck, and total body of patients with IGHD was 54, 71, and 59%, respectively, of that of age- and sex-matched controls (all P < 0 0.001). A similarly decreased BMC (42-69% of expected values) was found for all bone regions of patients with both OMPHD and CMPHD. Mean areal BMD measurements (g/cm(2)) varied (Z scores between -1.8 and -3.0), but the calculated true bone density (g/cm(3)) was normal in patients with IGHD or CMPHD and only slightly decreased (Z score, -0.8) in patients with OMPHD. Lifetime low-energy fracture prevalence was normal in patients with IGHD but substantially exceeded the expected prevalence in OMPHD (odds ratio of fracture = 3.0; 0.6 fractures per patient; P < 0.0001) or CMPHD patients (odds ratio for fracture = 7.4; 2.2 fractures per patient; P < 0.0001). In conclusion, IGHD and MPHD of childhood onset very substantially impair adult height and BMC. Although areal BMD is frankly decreased, volumetric bone density is unaffected, but nevertheless, the fracture prevalence in patients with MPHD is markedly increased. These observations demonstrate that not only volumetric density but also bone mass and shape are major determinants of bone strength.

Glycemic control with Humalog Mix25 in type 2 diabetes inadequately controlled with glyburide.

BACKGROUND: Humalog Mix25 (Mix25) is a premixed insulin mixture of 25% insulin lispro and 75% neutral protamine lispro. OBJECTIVE: The aim of this study was to quantitate the improvement in glycemic control achieved with Mix25 versus the maximum dose of glyburide (GB) in patients with type 2 diabetes inadequately controlled with GB. METHODS: In this randomized, parallel, open-label comparative study, patients with type 2 diabetes received either Mix25 before the morning and evening meals for 4 months or GB 15 mg daily for 4 months. Glycemic control was assessed by glycosylated hemoglobin (HbA1c) measurements, 4-point self-monitored blood glucose profiles, and patient-reported hypoglycemia. Patients also completed a treatment satisfaction questionnaire at the end of the study. RESULTS: All 172 patients were white; 85 were randomized to receive Mix25. The mean age was 59.5 +/- 8.2 years, and 35.5% (61/172) were men. The mean body mass index was 27.2 kg/m2. The mean duration of type 2 diabetes was 10.2 +/- 6.6 years, and the mean duration of sulfonylurea treatment was 5.8 +/- 5.9 years. The mean HbA1c and fasting blood glucose levels were 10.07% +/- 1.4% and 11.6 +/- 2.8 mmol/L, respectively, in the glyburide group and 9.85% +/- 1.2% and 12.2 +/- 2.9 mmol/L, respectively, in the Mix25 group. There were no statistically significant differences between the treatment groups at baseline for any of the demographic or efficacy variables. At end point, mean HbA1c was significantly lower in the Mix25 group than in the GB group (Mix25, 8.5% +/- 1.3%; GB, 9.4% +/- 1.8%; P = 0.001). A larger decrease from baseline in HbA1c and in all self-monitored blood glucose values was observed in the Mix25 group: -1.4% versus -0.7% for HbA1c, P = 0.004; -2.8 mmol/L versus -1.1 mmol/L for fasting blood glucose, P < 0.01; -5.1 mmol/L versus -1.7 mmol/L for the morning 2-hour postprandial blood glucose, P < 0.001; -2.2 mmol/L versus -0.8 mmol/L for the evening preprandial blood glucose, P < 0.05; and -4.4 mmol/L versus -1.5 mmol/L for the evening 2-hour postprandial blood glucose, P < 0.001. Patients expressed more satisfaction with Mix25 than with GB, as measured by the weighted combined score on a treatment satisfaction questionnaire (2.0 +/- 1.3 vs 0.7 +/- 1.3). The mean hypoglycemia rate (events per patient per 30 days) was significantly higher in the Mix25 group at end point (Mix25, 0.30 +/- 0.53; GB, 0.05 +/- 0.20; P < 0.001). CONCLUSIONS: Compared with maximum-dose GB, twice-daily injections of Mix25 resulted in improved glycemic control and treatment satisfaction, and were associated with a predictably higher rate of hypoglycemia in this group of patients with type 2 diabetes who were inadequately controlled with maximum-dose GB. Although the inclusion of patients who were inadequately controlled with GB was intended to allow a comparison of the 2 treatments with respect to efficacy and tolerability in a real-life setting, a double-blind comparison in treatment-naive individuals may have resulted in a different outcome.

[Clinical variants of McCune-Albright-Braitsev syndrome in girls]. / Klinicheskie varianty sindroma Mak-K'iuna-Olbraita-Braitseva u devochek.

The authors analyze published data on clinical variants and hormonal parameters in patients with this syndrome and present their own observations of children with this condition. Besides early sexual maturation, they describe the clinical picture of Cushing's syndrome, thyroid nodular hyperplasia. The said disorders do not depend on the tropic effect of the hypothalamohypophyseal system. A hypothesis is put forward about primary activation of adenylate cyclase system in the origin of the disease.