Body weight and eGFR during dulaglutide treatment in type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7).

In patients with type 2 dibetes and moderate-to-severe chronic kidney disease, dulaglutide treatment led to body weight (BW) loss and lesser eGFR decline compared to insulin glargine. As BW may affect muscle mass, creatinine-based eGFR can be altered independently of kidney function. Cystatin C-based eGFR is not affected by muscle mass.

Safety Outcomes During Pediatric GH Therapy: Final Results From the Prospective GeNeSIS Observational Program.

Context: Safety concerns have been raised regarding premature mortality, diabetes, neoplasia, and cerebrovascular disease in association with GH therapy.

Objective: To assess incidence of key safety outcomes.

Design: Prospective, multinational, observational study (1999 to 2015).

Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial.

Background: Many antihyperglycaemic drugs, including insulin, are primarily cleared by the kidneys, restricting treatment options for patients with kidney disease. Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist that is not cleared by the kidneys, and confers a lower risk of hypoglycaemia than does insulin. We assessed the efficacy and safety of dulaglutide in patients with type 2 diabetes and moderate-to-severe chronic kidney disease.

Mortality in Children Receiving Growth Hormone Treatment of Growth Disorders: Data From the Genetics and Neuroendocrinology of Short Stature International Study.

Context: Although pediatric growth hormone (GH) treatment is generally considered safe for approved indications, concerns have been raised regarding potential for increased risk of mortality in adults treated with GH during childhood.

Objective: To assess mortality in children receiving GH.

Design: Prospective, multinational, observational study.

Safety Outcomes and Near-Adult Height Gain of Growth Hormone-Treated Children with SHOX Deficiency: Data from an Observational Study and a Clinical Trial.

Background/aims: To assess auxological and safety data for growth hormone (GH)-treated children with SHOX deficiency.

Methods: Data were examined for GH-treated SHOX-deficient children (n = 521) from the observational Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS). For patients with near-adult height information, GeNeSIS results (n = 90) were compared with a clinical trial (n = 28) of SHOX-deficient patients.

Assessment of Primary Cancer Incidence in Growth Hormone-Treated Children: Comparison of a Multinational Prospective Observational Study with Population Databases.

Background/aims: Although results of the majority of clinical studies have shown no association between growth hormone (GH) treatment in childhood and risk of primary cancer, concerns remain regarding the potential influence of GH therapy on neoplastic cell growth. This study evaluated the incidence of primary malignancies in a large observational study of paediatric GH treatment.

Methods: Primary cancer incidence was assessed in a cohort of 19,054 GH-treated children without a reported prestudy history of malignancy in the observational Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS).

Efficacy and Safety of Once-Weekly Dulaglutide Versus Insulin Glargine in Patients With Type 2 Diabetes on Metformin and Glimepiride (AWARD-2).

Objective: This study compared the efficacy and safety of once-weekly dulaglutide, a glucagon-like peptide-1 receptor agonist, with daily insulin glargine, both combined with maximally tolerated doses of metformin and glimepiride in patients with type 2 diabetes. The primary objective was noninferiority of dulaglutide 1.5 mg to glargine in the HbA1c change from baseline at 52 weeks.

Radiological Features in Patients with Short Stature Homeobox-Containing (SHOX) Gene Deficiency and Turner Syndrome before and after 2 Years of GH Treatment.

Background/aims: The short stature homeobox-containing (SHOX) gene is one of many genes that regulate longitudinal growth. The SHOX deficiency (SHOX-D) phenotype, caused by intragenic or regulatory region defects, ranges from normal stature to mesomelic skeletal dysplasia. We investigated differences in radiological anomalies between patients with SHOX-D and Turner syndrome (TS) and the effect of 2 years of growth hormone (GH) treatment on these anomalies.

Safe and Effective Use of the Once Weekly Dulaglutide Single-Dose Pen in Injection-Naïve Patients With Type 2 Diabetes.

Background: This 4-week, phase 3b, multicenter, open-label, single-arm, outpatient study demonstrated the safe and effective use of the dulaglutide single-dose pen containing 0.5 mL of placebo for subcutaneous injection in injection-naïve adult patients with type 2 diabetes (T2D), with A1C ≤ 8.5% (69 mmol/mol), BMI ≥ 23 kg/m2 and ≤ 45 kg/m(2).

Incidence of primary cancers and intracranial tumour recurrences in GH-treated and untreated adult hypopituitary patients: analyses from the Hypopituitary Control and Complications Study.

Objective: Speculation remains that GH treatment is associated with increased neoplasia risk. Studies in GH-treated childhood cancer survivors suggested higher rates of second neoplasms, while cancer risk data for GH-treated and untreated hypopituitary adults have been variable. We present primary cancer risk data from the Hypopituitary Control and Complications Study (HypoCCS) with a focus on specific cancers, and assessment of recurrence rates for pituitary adenomas (PA) and craniopharyngiomas (CP).

Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with idiopathic isolated GH deficiency.

Objective: We assessed the characteristics of children initially diagnosed with idiopathic isolated GH deficiency (IGHD) who later developed additional (multiple) pituitary hormone deficiencies (MPHD).

Design: Data were analyzed for 5805 pediatric patients with idiopathic IGHD, who were GH-naïve at baseline and GH-treated in the multinational, observational Genetics and Neuroendocrinology of Short Stature International Study.

Methods: Development of MPHD was assessed from investigator diagnoses, adverse events, and concomitant medications.

GH treatment to final height produces similar height gains in patients with SHOX deficiency and Turner syndrome: results of a multicenter trial.

Context: Growth impairment in short stature homeobox-containing gene (SHOX) deficiency and Turner syndrome share a similar etiology. Because of the established effect of GH treatment on height in patients with Turner syndrome, we hypothesized that GH therapy would also stimulate growth in patients with SHOX deficiency.

Objective: Our objectives were to evaluate long-term efficacy of GH treatment in short patients with SHOX deficiency and to compare the effect on final (adult) height (FH) in patients with SHOX deficiency and Turner syndrome.

Associations between pituitary imaging abnormalities and clinical and biochemical phenotypes in children with congenital growth hormone deficiency: data from an international observational study.

Background/aims: Magnetic resonance imaging (MRI) is used to investigate the etiology of growth hormone deficiency (GHD). This study examined relationships between MRI findings and clinical/hormonal phenotypes in children with GHD in the observational Genetics and Neuroendocrinology of Short Stature International Study, GeNeSIS.

Methods: Clinical presentation, hormonal status and first-year GH response were compared between patients with pituitary imaging abnormalities (n = 1,071), patients with mutations in genes involved in pituitary development/GH secretion (n = 120) and patients with idiopathic GHD (n = 7,039).

Incidence of second neoplasm in childhood cancer survivors treated with GH: an analysis of GeNeSIS and HypoCCS.

Objective: Childhood cancer survivors are commonly treated with GH for GH deficiency that develops either as a result of primary malignancy or its treatment. One study--the Childhood Cancer Survivor Study (CCSS)--demonstrated increased risk of second neoplasm (SN) in GH-treated childhood cancer survivors compared with non-GH treated, after adjusting for key risk factors. We assessed the incidence of SN in GH-treated childhood cancer survivors in outpatient observational studies of GH replacement.

Prospective safety surveillance of GH-deficient adults: comparison of GH-treated vs untreated patients.

Context: In clinical practice, the safety profile of GH replacement therapy for GH-deficient adults compared with no replacement therapy is unknown.

Objective: The objective of this study was to compare adverse events (AEs) in GH-deficient adults who were GH-treated with those in GH-deficient adults who did not receive GH replacement.

Design And Setting: This was a prospective observational study in the setting of US clinical practices.

Assessment of primary cancers in GH-treated adult hypopituitary patients: an analysis from the Hypopituitary Control and Complications Study.

Objective: GH and IGFs have mitogenic properties, causing speculation that GH treatment could increase risk of malignancy. While studies in GH-treated childhood cancer survivors have suggested a slight increase in second neoplasms, studies in GH-treated adults have been equivocal. Design Incidence of de novo and second cancers was evaluated in 6840 GH-treated and 940 non GH-treated adult patients in the Hypopituitary Control and Complications Study pharmacoepidemiological database.

Effects of orally administered spinosad (Comfortis) in dogs on adult and immature stages of the cat flea (Ctenocephalides felis).

The efficacy of spinosad against adult fleas (Ctenocephalides felis) on dogs was evaluated in three controlled, blinded studies. One study was conducted to determine speed of kill on experimentally infested dogs. Two additional studies were designed to assess the efficacy of spinosad in preventing environmental contamination with flea eggs (USA study and EU study).

Metabolic, cardiovascular, and cerebrovascular outcomes in growth hormone-deficient subjects with previous cushing's disease or non-functioning pituitary adenoma.

Context: Previous exposure to hypercortisolism due to Cushing's disease (CD) may adversely affect long-term metabolic and cardiovascular outcomes. In particular, metabolic and cardiovascular outcomes of patients with previous CD who require GH replacement have not been fully established.

Objective: The aim of the study was to compare the prevalence and incidence of metabolic syndrome (Adult Treatment Panel III criteria), diabetes mellitus, cardiovascular disease, and cerebrovascular disease in GH-treated subjects with previous CD with GH-treated subjects with previous nonfunctioning pituitary adenoma (NFPA).

Prevalence of metabolic syndrome in adult hypopituitary growth hormone (GH)-deficient patients before and after GH replacement.

Context And Objective: Metabolic and body compositional consequences of GH deficiency (GHD) in adults are associated with a phenotype similar to the metabolic syndrome (MetS).

Patients: We assessed MetS prevalence in adult GHD patients (n = 2531) enrolled in the Hypopituitary Control and Complications Study. Prevalence was assessed at baseline and after 3 yr of GH replacement in a subset of 346 adult-onset patients.

Randomized, controlled clinical trial of the efficacy of fluoxetine for treatment of compulsive disorders in dogs.

Objective: To evaluate efficacy of fluoxetine hydrochloride for treatment of compulsive disorders in dogs.

Design: Randomized, controlled clinical trial.

Animals: 63 dogs with compulsive disorders.

Clinical field study of the safety and efficacy of spinosad chewable tablets for controlling fleas on dogs.

Preliminary studies showed spinosad to be rapidly effective and safe in controlling fleas on dogs. To validate these studies, a clinical trial was undertaken using 470 flea-infested client-owned dogs allocated to receive three monthly treatments with either beef-flavored chewable spinosad tablets (30-60 mg/kg) or selamectin applied according to label instructions. Flea counts 15 days after enrollment were reduced by 98.