Improvement of treatment adherence with growth hormone by easypod™ device: Experience of an Italian centre

Background: One of the most important vulnerabilities falling the efficacy of recombinant human growth hormone (r-hGH) treatment is low adherence especially in young patients. This study was planned to describe the correlation between r-hGH treatment efficacy and adherence in real-life setting using easypod™. Methods: Forty patients younger than 18 years, affected by a clinical condition in which r-hGH is available and treated with r-hGH easypod™, were enrolled in a retrospective, observational, real-world data, monocentric trial. The study design provided the retrospective collection of records collected by a questionnaire proposed to the patients and their parents and compared with registered data by the new generation electronic device r-hGH easypod™. Number of injections and doses were collected and used to assess the percentage of administered GH doses to measure treatment adherence. The r-hGH treatment efficacy was evaluated comparing standard deviation score for height (SDS) between baseline and follow-up visit, according to clinical practice. Results: The mean treatment adherence was 92.20% and it was inversely related to patients' age (R = - 0.358, p = 0.023), and significantly higher in the sub-group of patients with age between 10 and 13 years. Treatment adherence showed an inverse correlation with the years of therapy (R = - 0.453, p = 0.003) and with the number of r-hGH administrations (R = - 0.392, p = 0.012). However, the height increase did not reach a significant correlation with treatment adherence (R = - 0.067, p = 0.683). Conclusions: Children and adolescent patients with GH deficiency due to different clinical conditions show high adherence to r-hGH treatment tested by easypod™. Easypod™ could be used as an important device to control patients' adherence in daily treatment for chronic diseases with expensive drugs

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Rickets as Precocious Sign of Celiac Disease

Background: Vitamin D insufficiency is more frequent than expected also in Western Europe, however the relieve of a ‘health’ child with rickets is uncommon in Caucasians. Objective and hypotheses: Explain clinical severity by a genetic background. Method: We describe the clinical case of a 2.5-year-old girl with skeletal deformities. She was 86.5 cm (108 Cent), 12.5 kg (3–108 Cent); PH1B1. She showed typical rickets-linked signs (costochondral swelling; Harrison’s groove; genu varum; widening of wrist; skull bossing). She underwent a total-body X-ray study that showed: poor bone mineralization, femurs bowing; rachitic rosary; curved back; wrist and malleolus cupping. She had anamnestic record of insufficient sunlight exposure. She has four brothers with no signs of rickets. Blood examinations revealed: Ca: 8.7 mg/dl; P: 4.7 mg/dl; Mg: 2.45 mEq/l; alkaline phosphatase: 685 IU/l; 25-OHVitamin D: !7 ng/ml; PTH: 442 pg/ml (n.v.: 11–67); bone alkaline phosphatase: 21 (n.v.: 5–27); P1NP: 1044 (n.v.: 27–127); osteocalcin: 62.32 (n.v.: 1–11). Results: Deamidated gliadin antibodies were negative. However for the severe clinical presentation and the significant difference with the clinical condition of her brothers, she was studied for the genetic forms of vitamin D deficiency. The VDR gene did not show any mutation; however the gene carried a homozygous transition c.2TOC, considered a polymorphism. Furthermore a heterozygous polymorphism c.1056TOC was documented in exon 9. The sequence of CYP27B1 and PHEX genes was normal. She received vitamin D and calcium with a significant improvement of clinical, hematological, radiographic data. However she showed a significant increase of anti-transglutaminase antibodies (IgA): 89 U/ml; (IgG): 34 U/ml (n.v.: !4); Deamidated gliadin antibodies (IgA): 1.8; (IgG): 26 (n.v.: !7). Conclusion: The two polymorphisms (one heterozygous, associated with one homozygous) could explain the severity of rickets manifestations before celiac markers were detectable in our patient, highlighting the role of VDR polymorphisms in bone health and growth

Hypocomplementemia in children with juvenile idiopatic arthritis treated with tocilizumab: personal records

The relieve of a reduction in complement levels was recently reported in adults with Rheumatoid Arthritis treated with tocilizumab (TCZ). However, there are no data in children with Juvenile Idiopathic Arthritis (JIA) treated with TCZ

A Rare Case of Deletion in 2q24.1: Clinical Features and Response to Gh Hormone Treatment

Background: Chromosomal imbalances are often due to sub microscopic deletions or duplications not evidenced by conventional cytogenetic methods. Objective and hypotheses: CGH array can help in the diagnosis of severe short stature, associated with mental retardation and dysmorphisms. Method: We describe the clinical case of a 13.1-year-old girl, born at 35 weeks, from a triplets pregnancy. She was 127.5 cm (!K5 SDS), 33 kg (! K3 SDS); SPAN: 122 cm; PH2B2, bone age: 11 years; mild psychomotor delay, facial dysmorphism (malformed years with a low-set, microcephaly) and feet malformations (flexion deformities, broad halluces). Born SGA, with a growth velocity ! K3 SDS, a severe short stature she was a candidate to GH treatment. She started GH at the dosage of 0.035 mg/kg per day with a significant improvement of growth velocity. She had FSH, LH, TSH, fT4: in the normal range; low IGF-1 levels: 139 ng/ml (n.v. for age: 183–850). Results: CGH array evidenced a microdeletion of chromosome 2 (2q24.1), interesting genes UPP2, CCDC148, CCDC148-AS1, partially gene PKP4. MRI of CNS and pituitary revealed a small hypophysis with an intrasellar arachnoid cyst. After 11 months of GH treatment she was 134.8 cm (K3SDS), 37 kg; PH3B2. Conclusion: A few cases of deletion of 2q24 are reported in literature, and the association of low birth weight, growth delay, mental retardation, facial dysmorphism, cardiac malformations, feet and hands deformities is specific of this deletion. The mild phenotype of our patient could be explained by the small deletion (2q24.1). For this reason, it could be considered a continuous gene syndrome. At our knowledge this is the first case reported in the literature treated with GH and showing a satisfactory growth

GH TREATMENT ADHERENCE IN CHILDHOOD AND ADOLESCENCE IMPROVES USING EASYPODTM DEVICE: DATA DEMONSTRATION IN AN ITALIAN CENTRE

Objectives: Poor adherence to GH treatment is one of the pitfalls affecting the treatment efficacy. This study evaluates the GH treatment, using easypodTM in young patients over 6 months of therapy and describes the relationship between treatment efficacy and adherence. Methods: We collected the retrospective data registered in the electronic device easypodTM in 40 patients treated with GH. Number and doses of injection were used to calculate the percentage of treatment adherence. The inclusion criteria were: GH deficiency and the existence of one of the clinical condition in which GH is available: GHD, SGA, chronic renal failure, Turner syndrome. The GH efficacy was evaluated using the height gain in SD. Results: adherence was 92.20%, inversely related to patients’ age (p=0.023), significantly higher in patients with age 10-13 y. Adherence was inversely related to the y of therapy (p=0.003) and to the number of GH doses/week (p=0.012). Treatment efficacy did not correlate with adherence. Adherence showed a statistically significant correlation with IGF-1 (p=0.032). 35% referred discomfort at site of injection, 5% referred pain. The adherence was significantly lower in patients who self-injected GH (80.91%), compared to those treated by parents (95.2%) (p=0.002). 37.5% used all sites of injection, 32.5% refused 1 site, 12.5% 2, 17.5% used 1 site. The number of refused sites was inversely related to the adherence (p=0.011). The parents’ “level of education” did not show a statistically significant correlation with the adherence and data registered by the electronic device demonstrate that 35% of patients erroneously report their treatment adherence. Conclusions: Childhood and adolescent patients with GH deficiency show a high adherence to GH treatment monitored by easypodTM. Treatment adherence is inversely related to patients’ age, confirming the difficulties to treat chronic diseases especially in adolescence. The study suggests the importance of an electronic device able to measure adherence and easypodTM represents one of the most recent advances obtained in this field. This electronic device could represent a system to monitor patients’ adherence in chronic treatments, especially if they are expensive and self-managed by the family